Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	ACCEPT	Summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology. Reason: Accept as a supported cellular location. UniProt maps TRAPPC11 to the Golgi apparatus with PMID:27862579 support, and the CDG abstract reports delayed Golgi vesicular transport caused by TRAPPC11 mutation. Supporting Evidence: file:human/TRAPPC11/TRAPPC11-uniprot.txt Golgi apparatus {ECO:0000269\|PubMed:27862579} PMID:27862579 delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex PMID:21525244 RNAi against C8, C11, or C12 resulted in Golgi fragmentation
GO:0005737 cytoplasm	NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy.	ACCEPT	Summary: Cytoplasm is a broad but reasonable location for soluble/peripheral TRAPP complex biology. Reason: Accept as a broad supported location/context. TRAPP subunits have large soluble pools and function on early secretory pathway membranes; the more specific cytosol/Golgi locations are captured elsewhere. Supporting Evidence: PMID:21525244 Localization of subunits by fluorescence microscopy has proven difficult due to the large soluble pools of the proteins PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements Reactome:R-HSA-8877475 RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport	NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy.	ACCEPT	Summary: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII. Reason: Accept as a core process. TRAPPC11 was identified as a mammalian TRAPP component with C11-specific ER-to-ERGIC traffic evidence, and independent secretory-screen evidence shows human Gryzun/C4orf41 knockdown blocks Golgi exit. Supporting Evidence: PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit file:human/TRAPPC11/TRAPPC11-uniprot.txt Involved in endoplasmic reticulum to Golgi apparatus Reactome:R-HSA-8877475 RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
GO:0048208 COPII vesicle coat assembly	NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy.	MODIFY	Summary: The COPII coat assembly annotation captures early secretory context but overstates TRAPPC11 as a coat-assembly factor. Reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC11 evidence supports early ER/ERGIC/Golgi trafficking in COPII-associated anterograde traffic, not assembly of the COPII vesicle coat. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit Reactome:R-HSA-8877475 RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
GO:0099022 obsolete vesicle tethering	NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy.	MODIFY	Summary: The obsolete vesicle-tethering annotation should not be retained as-is. Reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported TRAPPC11/TRAPP process. Mammalian TRAPP tethering remains unresolved and this GO term is obsolete. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:27066478 evidence that any TRAPP complex acts as a membrane tether is currently inconclusive PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit
GO:1990072 TRAPPIII protein complex	NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy.	ACCEPT	Summary: TRAPPC11 is modeled as a mammalian TRAPPIII-associated subunit. Reason: Accept as core complex membership. TRAPPC11 is a metazoan TRAPP component assigned to mammalian TRAPP III in the review literature and independently described as a TRAPPIII subunit in the TRAPPC11-CDG abstract. Supporting Evidence: PMID:27066478 TRAPP III, which contains core TRAPP plus TrappC8, 11-13 PMID:27066478 TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13 PMID:27862579 delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex PMID:21525244 C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits Reactome:R-HSA-8877475 RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS)
GO:0045054 constitutive secretory pathway	IMP PMID:19942856 A genome-wide RNA interference screen identifies two novel c...	ACCEPT	Summary: TRAPPC11 is directly supported as an early secretory pathway factor. Reason: Accept as a supported core process at broad pathway level. The RNAi secretory screen shows human C4orf41/Gryzun blocks Golgi exit, and the TRAPP component paper places TRAPPC11 in early ER/ERGIC/Golgi trafficking. Supporting Evidence: PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway file:human/TRAPPC11/TRAPPC11-uniprot.txt Involved in endoplasmic reticulum to Golgi apparatus
GO:0005515 protein binding	IPI PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for TRAPPC11 function. Reason: Mark as over-annotated. The interaction evidence is better represented as TRAPP/TRAPPIII complex membership and TRAPP architecture/stability, not a generic protein binding molecular function. Supporting Evidence: PMID:21525244 C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits PMID:21525244 These results firmly establish the newly identified proteins as stable TRAPP interactors PMID:21525244 we report two novel TRAPP proteins, C4orf41/Gryzun (now designated TRAPPC11) and TTC-15 (now designated TRAPPC12) PMID:27066478 TrappC11, which is distantly related to Trs130/TrappC10, and TrappC12, were identified based on their co-fractionation with TRAPP and effect of their depletion on ER-to-Golgi transport
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport	IMP PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol...	ACCEPT	Summary: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII. Reason: Accept as a core process. TRAPPC11 was identified as a mammalian TRAPP component with C11-specific ER-to-ERGIC traffic evidence, and independent secretory-screen evidence shows human Gryzun/C4orf41 knockdown blocks Golgi exit. Supporting Evidence: PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit file:human/TRAPPC11/TRAPPC11-uniprot.txt Involved in endoplasmic reticulum to Golgi apparatus Reactome:R-HSA-8877475 RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
GO:0007030 Golgi organization	IMP PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol...	KEEP AS NON CORE	Summary: Golgi organization is a direct TRAPPC11-depletion phenotype but is secondary to early secretory trafficking. Reason: Keep as non-core. Golgi fragmentation is a useful readout of TRAPPC11/TRAPP disruption, while the core process is ER-to-ERGIC/Golgi trafficking and TRAPP complex stability. Supporting Evidence: PMID:21525244 RNAi against C8, C11, or C12 resulted in Golgi fragmentation PMID:21525244 These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway
GO:0030008 TRAPP complex	IMP PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol...	ACCEPT	Summary: TRAPPC11 is a mammalian TRAPP complex component. Reason: Accept as core cellular-component membership. TAP purification and coimmunoprecipitation identify C4orf41/TRAPPC11 as stably associated with mammalian TRAPP subunits. Supporting Evidence: PMID:21525244 C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits PMID:21525244 These results firmly establish the newly identified proteins as stable TRAPP interactors PMID:21525244 we report two novel TRAPP proteins, C4orf41/Gryzun (now designated TRAPPC11) and TTC-15 (now designated TRAPPC12) PMID:27066478 TrappC11, which is distantly related to Trs130/TrappC10, and TrappC12, were identified based on their co-fractionation with TRAPP and effect of their depletion on ER-to-Golgi transport file:human/TRAPPC11/TRAPPC11-uniprot.txt Component of the multisubunit TRAPP (transport protein
GO:0061635 regulation of protein complex stability	IMP PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol...	ACCEPT	Summary: TRAPPC11 supports mammalian TRAPP complex stability. Reason: Accept as a supported core process/function of TRAPPC11 within the TRAPP complex. C11 depletion partially disassembles the complex and the authors conclude that C11 stabilizes mammalian TRAPP. Supporting Evidence: PMID:21525244 depletion of C11 (Supplemental Figure 5) resulted in a partial disassembly of the TRAPP complex PMID:21525244 this protein stabilizes the TRAPP complex in mammalian cells
GO:0005794 Golgi apparatus	IDA PMID:27862579 Mutations in TRAPPC11 are associated with a congenital disor...	ACCEPT	Summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology. Reason: Accept as a supported cellular location. UniProt maps TRAPPC11 to the Golgi apparatus with PMID:27862579 support, and the CDG abstract reports delayed Golgi vesicular transport caused by TRAPPC11 mutation. Supporting Evidence: file:human/TRAPPC11/TRAPPC11-uniprot.txt Golgi apparatus {ECO:0000269\|PubMed:27862579} PMID:27862579 delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex PMID:21525244 RNAi against C8, C11, or C12 resulted in Golgi fragmentation
GO:0005829 cytosol	TAS Reactome:R-HSA-8877475	ACCEPT	Summary: Cytosol is consistent with TRAPPC11 as a soluble/peripheral TRAPP trafficking subunit. Reason: Accept as a supported location/context for TRAPPC11-containing TRAPP reactions. The complex is modeled as a cytosolic/peripheral trafficking GEF recruited to early secretory membranes. Supporting Evidence: PMID:21525244 Localization of subunits by fluorescence microscopy has proven difficult due to the large soluble pools of the proteins Reactome:R-HSA-8877475 RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0097352 autophagosome maturation	IMP PMID:31575891 Characterization of three TRAPPC11 variants suggests a criti...	NEW	Summary: TRAPPC11 supports autophagosome maturation/sealing in a variant-dependent mammalian cell context. Reason: Add as a new direct process annotation. Patient fibroblasts with TRAPPC11 variants show defective starvation-induced autophagic flux, poor LC3/LAMP1 colocalization, and failure to seal isolation membranes into autophagosomes; this is more specific than a generic autophagy row for the accessible evidence. Supporting Evidence: PMID:31575891 displayed an autophagic flux defect PMID:31575891 LC3-II could not be cleared from the cells over the time course of starvation examined PMID:31575891 poor starvation-dependent co-localization PMID:31575891 failed to seal isolation membranes into autophagosomes PMID:31575891 the extreme carboxy-terminus of TRAPPC11, but not residue Gly980, is critical for starvation-induced autophagy file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md defective starvation-induced autophagic flux

Core Functions

TRAPPC11 contributes a metazoan TRAPP/TRAPPIII-associated subunit needed for stable TRAPP architecture, early secretory pathway traffic between ER, ERGIC, and Golgi, and autophagosome maturation/sealing in variant-sensitive mammalian cell contexts. It should be modeled as contributing to complex-level TRAPP/RAB1 GEF activity and TRAPP stability rather than independently enabling GEF activity or COPII coat assembly.

Directly Involved In:

endoplasmic reticulum to Golgi vesicle-mediated transport constitutive secretory pathway regulation of protein complex stability autophagosome maturation

Cellular Locations:

cytosol cytoplasm Golgi apparatus

In Complex:

TRAPPIII protein complex

Supporting Evidence:

Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
PMID:27066478
TRAPP III, which contains core TRAPP plus TrappC8, 11-13
PMID:21525244
C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:21525244
Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment
PMID:21525244
knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment
PMID:21525244
TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
PMID:19942856
RNAi of human Gryzun (C4orf41) blocks Golgi exit
PMID:21525244
depletion of C11 (Supplemental Figure 5) resulted in a partial disassembly of the TRAPP complex
PMID:21525244
this protein stabilizes the TRAPP complex in mammalian cells
file:human/TRAPPC11/TRAPPC11-uniprot.txt
Golgi apparatus {ECO:0000269|PubMed:27862579}
PMID:31575891
displayed an autophagic flux defect
PMID:31575891
LC3-II could not be cleared from the cells over the time course of starvation examined
PMID:31575891
failed to seal isolation membranes into autophagosomes

References

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:19942856

A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway.

PMID:21525244

C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.

PMID:27066478

TRAPP Complexes in Secretion and Autophagy.

PMID:27862579

Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation.

PMID:31575891

Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein.

Reactome:R-HSA-8877475

TRAPPC complexes exchange GTP for GDP on RAB1

file:human/TRAPPC11/TRAPPC11-uniprot.txt

UniProtKB record for TRAPPC11

file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md

Falcon deep research report for TRAPPC11

Suggested Experiments

Experiment: Rescue TRAPPC11-depleted cells with wild-type and disease-associated TRAPPC11 variants, then measure VSV-G ER-to-ERGIC/Golgi transport, Golgi morphology, and TRAPP complex assembly by native fractionation.

Hypothesis: TRAPPC11 supports early secretory transport by stabilizing mammalian TRAPP/TRAPPIII architecture.

Type: secretory cargo rescue and complex stability assay

Experiment: Reconstitute TRAPPC11-containing TRAPPIII and measure RAB1 GDP-to-GTP exchange with and without TRAPPC11 depletion or mutant replacement.

Hypothesis: TRAPPC11 contributes to complex-level TRAPPIII/RAB1 GEF function through assembly or stabilization rather than acting as an independent GEF.

Type: complex reconstitution and RAB1 GEF assay

Experiment: Test TRAPPC11 knockdown/rescue and C-terminal disease variants in starvation-induced LC3-II clearance, LC3/LAMP1 colocalization, and protease protection assays alongside ER-Golgi cargo transport.

Hypothesis: TRAPPC11 C-terminal integrity is required for autophagosome maturation or sealing and can be separated experimentally from some ER-Golgi transport defects.

Type: parallel autophagosome maturation and secretion assay

Deep Research

Falcon

(TRAPPC11-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 23 citations 2 artifacts 2026-06-02T02:44:17.583455

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000022 Figure 2 from the document illustrates the metazoan TRAPP complexes and their subunit compositions. - **Panel (A)** lists the core (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Human TRAPPC11 (UniProt Q7Z392; gene TRAPPC11; synonym C4orf41)—functional annotation

1) Identity verification and key definitions (current understanding)

Gene/protein identity. Primary proteomic purification of the mammalian TRAPP complex identified the human gene C4orf41 as a bona fide TRAPP component and designated it TRAPPC11 (Trafficking protein particle complex subunit 11). This work placed TRAPPC11 functionally in the early secretory pathway, specifically ER-to-Golgi trafficking at/near the ERGIC. Publication date: 2011-06. URL: https://doi.org/10.1091/mbc.e10-11-0873 (scrivens2011c4orf41andttc15 pages 1-2, scrivens2011c4orf41andttc15 pages 2-3).

TRAPP complexes (concept). TRAPP (TRAnsport Protein Particle) complexes are multisubunit Rab GTPase guanine-nucleotide exchange factors (GEFs) and tethering-related assemblies that organize vesicle trafficking. In metazoans, there are two major TRAPP complexes:
- TRAPPII, which preferentially activates Rab11
- TRAPPIII, which preferentially activates Rab1
Publication date: 2023-12. URL: https://doi.org/10.1002/1873-3468.14553 (Figure summarizes composition and Rab specificity) (galindo2023thetrappcomplexes media bb790abc).

Where TRAPPC11 fits. Recent synthesis/reviews place TRAPPC11 as a TRAPPIII-associated subunit (metazoan-specific; no yeast homologue), contributing to TRAPPIII architecture and function. Publication date: 2023-12. URL: https://doi.org/10.1016/j.jacbts.2023.03.011 (papaioannou2023biochemicalstructureand pages 4-5).

2) Molecular function, pathways, and subcellular localization (evidence-based)

2.1 Primary cellular role: early secretory pathway trafficking (ER → ERGIC → Golgi)

Loss-of-function phenotypes. RNAi depletion of TRAPPC11 causes (i) Golgi fragmentation and (ii) arrest of anterograde cargo trafficking at an early step—VSV-G cargo fails to reach the Golgi efficiently and accumulates in BFA-resistant puncta colocalizing with ERGIC markers, consistent with a block at ER exit sites/peripheral ERGIC. Publication date: 2011-06. URL: https://doi.org/10.1091/mbc.e10-11-0873 (scrivens2011c4orf41andttc15 pages 6-7).

Patient-cell trafficking defects. Patient-derived fibroblasts with bi-allelic TRAPPC11 variants show delayed ER-to-Golgi transport and/or delayed exit from the Golgi, supporting a conserved requirement for TRAPPC11 in secretory trafficking. Publication date: 2019-10. URL: https://doi.org/10.1038/s41598-019-50415-6 (milev2019characterizationofthree pages 1-2).

Localization context (functional compartment). Across studies, the functional readouts consistently implicate TRAPPC11 activity at the ER–Golgi interface (ERGIC/Golgi) rather than at the plasma membrane or nucleus, consistent with a TRAPP complex subunit operating on secretory pathway membranes (scrivens2011c4orf41andttc15 pages 6-7, milev2019characterizationofthree pages 1-2).

2.2 Complex membership and Rab pathway assignment (Rab1-centric TRAPPIII)

Consensus composition and Rab specificity (2023). A 2023 FEBS Letters review provides a consolidated metazoan TRAPP model in which TRAPPC11 is TRAPPIII-specific, and illustrates that TRAPPIII activates Rab1 while TRAPPII activates Rab11 (with shared core subunits). Publication date: 2023-12. URL: https://doi.org/10.1002/1873-3468.14553 (figure evidence) (galindo2023thetrappcomplexes media bb790abc).

Structural/assembly role. A 2023 review focused on TRAPP complexes (with cryo-EM-informed models) describes TRAPPC11 as a metazoan TRAPPIII-associated subunit that binds TRAPPC2L and occupies a position where its C-terminal region meets TRAPPC8 at an outer “vertex” that also includes TRAPPC12/13—consistent with a scaffolding/assembly role rather than an enzymatic catalytic role. Publication date: 2023-12. URL: https://doi.org/10.1016/j.jacbts.2023.03.011 (papaioannou2023biochemicalstructureand pages 4-5).

2.3 Glycosylation: TRAPPC11-linked hypoglycosylation in disease and models

Dystroglycan hypoglycosylation (disease-relevant). A 2024 TRAPPopathies review summarizes that TRAPPC11 variants are associated with protein hypoglycosylation, including severe hypoglycosylation of α-dystroglycan in affected tissues (muscle/brain), and that TRAPPC11 depletion causes hypoglycosylation phenotypes in human cells and vertebrate models. Publication date: 2024-12. URL: https://doi.org/10.3390/ijms252413329 (hall2024trappopathiesseveremultisystem pages 12-14).

Mechanistic interpretation. The most supported mechanistic interpretation from available evidence is that TRAPPC11-dependent secretory pathway organization and Golgi/ERGIC integrity are required for normal maturation/processing of glycoproteins (including glycosylation-dependent epitopes such as α-dystroglycan), though tissue-specificity is reported (e.g., fibroblasts can show less severe α-dystroglycan labeling changes than muscle). (hall2024trappopathiesseveremultisystem pages 12-14).

2.4 Autophagy: role in autophagosome maturation/sealing

Patient-cell autophagic flux phenotypes. In patient fibroblasts, TRAPPC11 variants can cause defective starvation-induced autophagic flux with failure to clear LC3-II and reduced LC3–LAMP1 colocalization; a protease-protection assay supported accumulation of unsealed isolation membranes, consistent with a block in autophagosome completion. Publication date: 2019-10. URL: https://doi.org/10.1038/s41598-019-50415-6 (milev2019characterizationofthree pages 10-11).

Mechanistic placement (2023). A 2023 synthesis places TRAPPC11 function downstream of isolation membrane initiation, where TRAPPC11 contributes to recruiting factors (e.g., ATG2, WIPI4/WDR45) required for sealing to form mature autophagosomes. (almousa2023insightintotrappii pages 28-32).

3) Recent developments (prioritizing 2023–2024)

3.1 Updated TRAPP complex models (composition, Rab specificity, and membrane context)

Metazoan TRAPP composition clarified with structure-informed schematics. A 2023 FEBS Letters review provides a figure consolidating TRAPPII vs TRAPPIII composition and explicitly places TRAPPC11 in TRAPPIII with Rab1 specificity (TRAPPII→Rab11). Publication date: 2023-12. URL: https://doi.org/10.1002/1873-3468.14553 (galindo2023thetrappcomplexes media bb790abc).
Assembly/architecture emphasis. A 2023 JACC: Basic to Translational Science review (cardiac-focused) uses structural interpretations to highlight how TRAPPC11 contributes to TRAPPIII architecture via TRAPPC2L binding and positioning with TRAPPC8/12/13, emphasizing that peripheral subunits shape specificity and membrane-contextual function. Publication date: 2023-12. URL: https://doi.org/10.1016/j.jacbts.2023.03.011 (papaioannou2023biochemicalstructureand pages 4-5).

3.2 2023 cohort expansion and quantitative phenotyping of TRAPPC11 disease

A 2023 Journal of Medical Genetics cohort study reported 25 Roma individuals homozygous for a founder TRAPPC11 splice variant (c.1287+5G>A), substantially expanding systematic phenotyping. Publication date: 2023-05. URL: https://doi.org/10.1136/jmg-2022-109132 (justel2023expandingthephenotypic pages 2-3).

Key quantitative findings from this cohort include:
- Global psychomotor delay: 96% (24/25)
- Motor delay as presenting feature: 84% (21/25)
- Intellectual disability in individuals >4 years: 100% (23/23), with reported severity distribution (severe/moderate/mild categories)
These data support TRAPPC11 deficiency as a neurodevelopmental + myopathic disorder with frequent microcephaly and susceptibility to infection-triggered decompensation described as “pseudometabolic crises.” (justel2023expandingthephenotypic pages 2-3).

3.3 2024 review-level consolidation: variant landscape and cellular readouts

A 2024 International Journal of Molecular Sciences review consolidates clinical genetics and experimental cell biology across TRAPPopathies and notes that ClinVar lists >60 pathogenic/likely pathogenic autosomal-recessive TRAPPC11 variants, highlighting the growing diagnostic landscape and allelic heterogeneity. Publication date: 2024-12. URL: https://doi.org/10.3390/ijms252413329 (hall2024trappopathiesseveremultisystem pages 12-14).

4) Current applications and real-world implementations

Clinical implementation. TRAPPC11 is implicated in autosomal-recessive limb-girdle muscular dystrophy subtype LGMD R18 (also referred to historically as LGMD2S) and TRAPPC11-related congenital disorder of glycosylation phenotypes; modern clinical practice commonly uses NGS gene panels / WES for suspected muscular dystrophy and neurodevelopmental disorders.

Evidence for real-world sequencing cohorts:
- In a 2023 Turkish referral cohort of 256 individuals with neurological presentations, one case carried a homozygous TRAPPC11 p.(Gly980Arg) variant and presented with muscular dystrophy, cataract, neuromotor retardation, and microcephaly. Publication date: 2023-09. URL: https://doi.org/10.26650/jchild.2023.1294229 (aslanger2023clinicalradiologicaland pages 1-2).

4.2 Cellular assays as functional implementation (research and variant interpretation)

Patient fibroblast assays as a functional readout. Multiple studies and reviews emphasize use of patient fibroblasts to measure:
- VSV-G-ts045-GFP trafficking kinetics (ER-to-Golgi and Golgi exit delay)
- Golgi morphology (fragmentation/dispersal)
- glycosylation markers (including α-dystroglycan hypoglycosylation in muscle)
- autophagy flux assays (LC3-II, LC3/LAMP1 colocalization, protease protection)
These represent “real-world” experimental implementations used to connect genotype to mechanism and support variant pathogenicity interpretation. (hall2024trappopathiesseveremultisystem pages 12-14, milev2019characterizationofthree pages 10-11, scrivens2011c4orf41andttc15 pages 6-7).

5) Expert synthesis and analysis (authoritative interpretations)

Primary functional role (most supported). Across primary cell biology and disease-cell phenotyping, TRAPPC11 most strongly supports a scaffolding/assembly role within TRAPPIII at the ER–Golgi interface, impacting:
1) early anterograde secretory trafficking (ER/ERGIC → Golgi) and Golgi integrity, and
2) downstream consequences for glycoprotein maturation/glycosylation and autophagosome maturation.
This interpretation is directly supported by early mechanistic cell biology (RNAi + cargo trafficking arrest) and reinforced by patient fibroblast phenotypes (trafficking delay, Golgi dispersal, glycosylation and autophagy readouts) as consolidated in 2024 review literature. (scrivens2011c4orf41andttc15 pages 6-7, milev2019characterizationofthree pages 1-2, hall2024trappopathiesseveremultisystem pages 12-14).

Not an enzyme with a defined substrate reaction. The evidence indicates TRAPPC11 is not primarily a catalytic enzyme; rather, it is a complex subunit whose “substrate specificity” is best conceptualized at the pathway level (i.e., regulating Rab1-associated trafficking via TRAPPIII organization and membrane-context function). (papaioannou2023biochemicalstructureand pages 4-5, galindo2023thetrappcomplexes media bb790abc).

Domain/family note. The provided UniProt/domain context (TPC11/TRAPPC11_C/Foie-gras/Gryzun-like) is consistent with disease and variant analyses emphasizing functional importance of the C-terminal region and regions including a “foie gras” domain deletion variant; patient variant characterization supports the C-terminus as critical for cellular phenotypes. Publication date: 2019-10. URL: https://doi.org/10.1038/s41598-019-50415-6 (milev2019characterizationofthree pages 1-2, milev2019characterizationofthree pages 10-11).

Visual evidence (TRAPP model including TRAPPC11)

A 2023 figure summarizing metazoan TRAPP complex composition and Rab specificity explicitly places TRAPPC11 in TRAPPIII and depicts TRAPPIII→Rab1 vs TRAPPII→Rab11. Publication date: 2023-12. URL: https://doi.org/10.1002/1873-3468.14553 (galindo2023thetrappcomplexes media bb790abc).

Summary table (evidence-based functional annotation)

Function/Process	Evidence type (review/primary, assay)	Key findings	Subcellular location/compartment	Key interaction/complex context (TRAPPII/TRAPPIII, Rab1/Rab11)	Citations (pqac IDs)
Gene/protein identity and complex membership	Primary; tandem-affinity purification/proteomics and interaction mapping	Human C4orf41 is TRAPPC11, a bona fide mammalian TRAPP subunit; recovered with known TRAPP baits and implicated in early secretory trafficking	TRAPP-associated membranes of the early secretory pathway	TRAPP complex component; later literature places it in metazoan TRAPPIII	(scrivens2011c4orf41andttc15 pages 1-2, scrivens2011c4orf41andttc15 pages 2-3, papaioannou2023biochemicalstructureand pages 4-5)
Early ER-to-Golgi trafficking	Primary; RNAi depletion, VSV-G transport assay, fluorescence microscopy, BFA perturbation	TRAPPC11 depletion causes cargo arrest before/at ERGIC and Golgi fragmentation; VSV-G fails to efficiently reach/pass through Golgi	ER exit sites, ERGIC, Golgi	TRAPP-mediated early secretory pathway function; TRAPPIII-associated in later models	(scrivens2011c4orf41andttc15 pages 1-2, scrivens2011c4orf41andttc15 pages 6-7, hall2024trappopathiesseveremultisystem pages 12-14)
Golgi organization/integrity	Primary and review; patient fibroblast imaging, immunoblot	Loss or mutation of TRAPPC11 leads to Golgi dispersal/fragmentation and reduced full-length TRAPPC11 protein	Golgi apparatus	Loss of interaction with TRAPP core, especially TRAPPC2, is reported for disease variants	(hall2024trappopathiesseveremultisystem pages 12-14, maeda2025disease‐associatedfactorsat pages 8-9)
Rab GEF pathway assignment	Reviews/structural synthesis; cryo-EM-informed models	In metazoans, TRAPPC11 is assigned to TRAPPIII, the complex that activates Rab1; TRAPPII activates Rab11	Membrane-associated TRAPP complexes on secretory/autophagy membranes	TRAPPIII-specific subunit; Rab1 pathway, contrasted with TRAPPII/Rab11	(almousa2023insightintotrappii pages 28-32, papaioannou2023biochemicalstructureand pages 4-5, almousa2023insightintotrappii pages 24-28, galindo2023thetrappcomplexes media bb790abc)
TRAPPIII architecture/assembly	Structural review; cryo-EM/density-map interpretation	TRAPPC11 is metazoan-specific, binds TRAPPC2L, and its C-terminal region meets TRAPPC8 at the outer TRAPPIII architecture vertex with TRAPPC12/13	TRAPPIII complex scaffold at membrane surface	TRAPPIII assembly with TRAPPC8/12/13; contributes to Rab1-specific complex organization	(papaioannou2023biochemicalstructureand pages 4-5, galindo2023thetrappcomplexes media bb790abc)
Protein glycosylation	Primary and review; patient biopsies/fibroblasts, immunoblot, glycosylation markers	TRAPPC11 deficiency causes protein hypoglycosylation; severe α-dystroglycan hypoglycosylation is seen in affected muscle/brain, with altered N-glycosylation markers in cells	ER/Golgi glycoprotein processing pathway	Function extends beyond generic trafficking; may include TRAPP-independent effects on N-linked glycosylation/LLO homeostasis	(hall2024trappopathiesseveremultisystem pages 12-14, milev2019characterizationofthree pages 10-11, almousa2023insightintotrappii pages 28-32)
Autophagy/autophagosome maturation	Primary and review; LC3-II flux, LC3-LAMP1 colocalization, protease-protection assay	TRAPPC11 acts upstream of autophagosome sealing; deficiency reduces autophagic flux and yields unsealed isolation membranes in some patient cells	Isolation membrane/autophagosome, lysosome-related compartments	TRAPPIII-associated autophagy role; recruits/acts with autophagy machinery downstream of initiation	(milev2019characterizationofthree pages 1-2, milev2019characterizationofthree pages 10-11, almousa2023insightintotrappii pages 28-32, hall2024trappopathiesseveremultisystem pages 12-14)
Lysosomal/autophagic marker changes	Review of primary patient-cell work; LAMP1 localization/levels	Altered LAMP1 localization and reduced LAMP1 levels in patient fibroblasts support lysosomal/autophagic perturbation	Lysosome/autolysosome-related compartments	Downstream consequence of TRAPPC11 dysfunction within TRAPPIII-linked trafficking/autophagy networks	(hall2024trappopathiesseveremultisystem pages 12-14)
Functional importance of C-terminus/domains	Primary; variant analysis in patient cells	Variants affecting the foie gras region or extreme carboxy terminus impair trafficking, glycosylation, and in some cases autophagy, indicating the C-terminus is critical for function	TRAPPIII structural subunit with functionally important C-terminal region	Supports structural role within TRAPPIII rather than enzyme catalysis	(milev2019characterizationofthree pages 1-2, milev2019characterizationofthree pages 10-11)
Disease-relevant cellular role	Review and primary human genetics/cell biology	TRAPPC11 variants cause multisystem “TRAPPopathy” with consistent muscle involvement and cellular defects in trafficking, Golgi maintenance, glycosylation, and autophagy	Highest functional readout in muscle, fibroblasts, liver-related pathways	Autosomal-recessive TRAPPC11 deficiency; ClinVar lists >60 pathogenic/likely pathogenic variants	(hall2024trappopathiesseveremultisystem pages 12-14)

Table: This table summarizes the experimentally supported functional annotation of human TRAPPC11 (UniProt Q7Z392), including trafficking, Golgi, glycosylation, and autophagy roles. It also captures the current consensus that TRAPPC11 is a metazoan TRAPPIII subunit linked to Rab1 rather than Rab11 biology.

Key takeaways

TRAPPC11 (C4orf41; UniProt Q7Z392) is a bona fide TRAPP subunit required for efficient ER-to-Golgi trafficking and maintaining Golgi/ERGIC organization (scrivens2011c4orf41andttc15 pages 6-7, scrivens2011c4orf41andttc15 pages 1-2).
Current 2023–2024 synthesis places TRAPPC11 as TRAPPIII-associated, supporting Rab1 pathway function and TRAPPIII architecture (galindo2023thetrappcomplexes media bb790abc, papaioannou2023biochemicalstructureand pages 4-5).
In humans, bi-allelic TRAPPC11 variants cause multisystem disease (LGMD R18 / TRAPPC11-CDG spectrum) with quantifiable neurodevelopmental and myopathic phenotypes; a 2023 cohort of 25 founder homozygotes provides robust statistics on developmental delay and intellectual disability (justel2023expandingthephenotypic pages 2-3).
Mechanistic cellular consequences include glycosylation defects (e.g., α-dystroglycan hypoglycosylation in tissues) and autophagy maturation defects in some variant contexts (hall2024trappopathiesseveremultisystem pages 12-14, milev2019characterizationofthree pages 10-11).

References

(scrivens2011c4orf41andttc15 pages 1-2): P. James Scrivens, Baraa Noueihed, Nassim Shahrzad, Sokunthear Hul, Stephanie Brunet, and Michael Sacher. C4orf41 and ttc-15 are mammalian trapp components with a role at an early stage in er-to-golgi trafficking. Molecular Biology of the Cell, 22:2083-2093, Jun 2011. URL: https://doi.org/10.1091/mbc.e10-11-0873, doi:10.1091/mbc.e10-11-0873. This article has 150 citations and is from a domain leading peer-reviewed journal.
(scrivens2011c4orf41andttc15 pages 2-3): P. James Scrivens, Baraa Noueihed, Nassim Shahrzad, Sokunthear Hul, Stephanie Brunet, and Michael Sacher. C4orf41 and ttc-15 are mammalian trapp components with a role at an early stage in er-to-golgi trafficking. Molecular Biology of the Cell, 22:2083-2093, Jun 2011. URL: https://doi.org/10.1091/mbc.e10-11-0873, doi:10.1091/mbc.e10-11-0873. This article has 150 citations and is from a domain leading peer-reviewed journal.
(galindo2023thetrappcomplexes media bb790abc): Antonio Galindo and Sean Munro. The trapp complexes: oligomeric exchange factors that activate the small gtpases rab1 and rab11. FEBS Letters, 597:734-749, Dec 2023. URL: https://doi.org/10.1002/1873-3468.14553, doi:10.1002/1873-3468.14553. This article has 24 citations and is from a peer-reviewed journal.
(papaioannou2023biochemicalstructureand pages 4-5): Peter Papaioannou, Michael J. Wallace, Nipun Malhotra, Peter J. Mohler, and Mona El Refaey. Biochemical structure and function of trapp complexes in the cardiac system. Dec 2023. URL: https://doi.org/10.1016/j.jacbts.2023.03.011, doi:10.1016/j.jacbts.2023.03.011. This article has 10 citations.
(scrivens2011c4orf41andttc15 pages 6-7): P. James Scrivens, Baraa Noueihed, Nassim Shahrzad, Sokunthear Hul, Stephanie Brunet, and Michael Sacher. C4orf41 and ttc-15 are mammalian trapp components with a role at an early stage in er-to-golgi trafficking. Molecular Biology of the Cell, 22:2083-2093, Jun 2011. URL: https://doi.org/10.1091/mbc.e10-11-0873, doi:10.1091/mbc.e10-11-0873. This article has 150 citations and is from a domain leading peer-reviewed journal.
(milev2019characterizationofthree pages 1-2): Miroslav P. Milev, Daniela Stanga, Anne Schänzer, Andrés Nascimento, Djenann Saint-Dic, Carlos Ortez, Daniel Natera-de Benito, Desiré González Barrios, Jaume Colomer, Carmen Badosa, Cristina Jou, Pia Gallano, Lidia Gonzalez-Quereda, Ana Töpf, Katherine Johnson, Volker Straub, Andreas Hahn, Michael Sacher, and Cecilia Jimenez-Mallebrera. Characterization of three trappc11 variants suggests a critical role for the extreme carboxy terminus of the protein. Scientific Reports, Oct 2019. URL: https://doi.org/10.1038/s41598-019-50415-6, doi:10.1038/s41598-019-50415-6. This article has 19 citations and is from a peer-reviewed journal.
(hall2024trappopathiesseveremultisystem pages 12-14): Riley Hall, Vallari Sawant, Jinchao Gu, Tim Sikora, Ben Rollo, Silvia Velasco, Jinkuk Kim, Nava Segev, John Christodoulou, and Nicole J. Van Bergen. Trappopathies: severe multisystem disorders caused by variants in genes of the transport protein particle (trapp) complexes. Dec 2024. URL: https://doi.org/10.3390/ijms252413329, doi:10.3390/ijms252413329. This article has 7 citations.
(milev2019characterizationofthree pages 10-11): Miroslav P. Milev, Daniela Stanga, Anne Schänzer, Andrés Nascimento, Djenann Saint-Dic, Carlos Ortez, Daniel Natera-de Benito, Desiré González Barrios, Jaume Colomer, Carmen Badosa, Cristina Jou, Pia Gallano, Lidia Gonzalez-Quereda, Ana Töpf, Katherine Johnson, Volker Straub, Andreas Hahn, Michael Sacher, and Cecilia Jimenez-Mallebrera. Characterization of three trappc11 variants suggests a critical role for the extreme carboxy terminus of the protein. Scientific Reports, Oct 2019. URL: https://doi.org/10.1038/s41598-019-50415-6, doi:10.1038/s41598-019-50415-6. This article has 19 citations and is from a peer-reviewed journal.
(almousa2023insightintotrappii pages 28-32): H Almousa. Insight into trappii assembly and function through characterization of naturally occurring trapp gene variants. Unknown journal, 2023.
(justel2023expandingthephenotypic pages 2-3): Maria Justel, Cristina Jou, Andrea Sariego-Jamardo, Natalia Alexandra Juliá-Palacios, Carlos Ortez, Maria Luisa Poch, Antonio Hedrera-Fernandez, Hilario Gomez-Martin, Anna Codina, Jana Dominguez-Carral, Jordi Muxart, Aurelio Hernández-Laín, Sara Vila-Bedmar, Miren Zulaica, Ramon Cancho-Candela, Margarita del Carmen Castro, Alberto de la Osa-Langreo, Alfonso Peña-Valenceja, Elena Marcos-Vadillo, Pablo Prieto-Matos, Samuel Ignacio Pascual-Pascual, Adolfo López de Munain, Ana Camacho, Berta Estevez-Arias, Uliana Musokhranova, Mireia Olivella, Alfonso Oyarzábal, Cecilia Jimenez-Mallebrera, Cristina Domínguez-González, Andrés Nascimento, Àngels García-Cazorla, and Daniel Natera-de Benito. Expanding the phenotypic spectrum of trappc11-related muscular dystrophy: 25 roma individuals carrying a founder variant. Journal of Medical Genetics, 60:965-973, May 2023. URL: https://doi.org/10.1136/jmg-2022-109132, doi:10.1136/jmg-2022-109132. This article has 12 citations and is from a domain leading peer-reviewed journal.
(aslanger2023clinicalradiologicaland pages 1-2): Ayça Aslanger, Esma Sengenç, Emrah Yücesan, Beyza Göncü, Akın İşcan, and Gözde Yeşil Sayın. Clinical, radiological, and molecular findings in cases with trappopathies. Çocuk Dergisi / Journal of Child, 23:1-7, Sep 2023. URL: https://doi.org/10.26650/jchild.2023.1294229, doi:10.26650/jchild.2023.1294229. This article has 0 citations.
(maeda2025disease‐associatedfactorsat pages 8-9): Miharu Maeda, Masashi Arakawa, and Kota Saito. Disease‐associated factors at the endoplasmic reticulum–golgi interface. Traffic (Copenhagen, Denmark), Jan 2025. URL: https://doi.org/10.1111/tra.70001, doi:10.1111/tra.70001. This article has 2 citations.
(almousa2023insightintotrappii pages 24-28): H Almousa. Insight into trappii assembly and function through characterization of naturally occurring trapp gene variants. Unknown journal, 2023.

Artifacts

Edison artifact artifact-00

Citations

papaioannou2023biochemicalstructureand pages 4-5
milev2019characterizationofthree pages 1-2
hall2024trappopathiesseveremultisystem pages 12-14
milev2019characterizationofthree pages 10-11
almousa2023insightintotrappii pages 28-32
justel2023expandingthephenotypic pages 2-3
aslanger2023clinicalradiologicaland pages 1-2
almousa2023insightintotrappii pages 24-28
https://doi.org/10.1091/mbc.e10-11-0873
https://doi.org/10.1002/1873-3468.14553
https://doi.org/10.1016/j.jacbts.2023.03.011
https://doi.org/10.1038/s41598-019-50415-6
https://doi.org/10.3390/ijms252413329
https://doi.org/10.1136/jmg-2022-109132
https://doi.org/10.26650/jchild.2023.1294229
https://doi.org/10.1091/mbc.e10-11-0873,
https://doi.org/10.1002/1873-3468.14553,
https://doi.org/10.1016/j.jacbts.2023.03.011,
https://doi.org/10.1038/s41598-019-50415-6,
https://doi.org/10.3390/ijms252413329,
https://doi.org/10.1136/jmg-2022-109132,
https://doi.org/10.26650/jchild.2023.1294229,
https://doi.org/10.1111/tra.70001,

📚 Additional Documentation

Notes

(TRAPPC11-notes.md)

TRAPPC11 review notes

TRAPPC11 (C4orf41/Gryzun) is a metazoan TRAPP-associated subunit. Scrivens et al. identify C4orf41/Gryzun as TRAPPC11 and report that C8, C11, and C12 are bona fide TRAPP components with roles in ER-to-Golgi trafficking, specifically implicating C11 in ER-to-ERGIC membrane traffic [PMID:21525244 "we report two novel TRAPP proteins, C4orf41/Gryzun (now designated TRAPPC11)" and "Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment"].

The same paper supports TRAPP complex membership by TAP purification and coimmunoprecipitation. TRAPPC11 and TRAPPC12 interact with each other and established TRAPP subunits, and the newly identified proteins are stable TRAPP interactors [PMID:21525244 "C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits" and "These results firmly establish the newly identified proteins as stable TRAPP interactors"].

TRAPPC11 appears to help stabilize mammalian TRAPP architecture. C11 depletion partially redistributes core TRAPP signals out of the high-molecular-weight pool and affects C12 levels, leading the authors to conclude that C11 stabilizes mammalian TRAPP [PMID:21525244 "depletion of C11 ... resulted in a partial disassembly of the TRAPP complex" and "this protein stabilizes the TRAPP complex in mammalian cells"].

TRAPPC11 supports early secretory/ER-to-Golgi trafficking rather than COPII coat assembly per se. TRAPPC11/C12 knockdown arrests VSV-G cargo in a BFA-resistant ERGIC-associated compartment, and the authors model TRAPP function at ER exit sites or peripheral ERGIC elements [PMID:21525244 "knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment" and "TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements"].

TRAPPC11 depletion also produces Golgi fragmentation, which is best interpreted as a phenotype/readout of early secretory pathway disruption rather than the most specific core process [PMID:21525244 "RNAi against C8, C11, or C12 resulted in Golgi fragmentation" and "These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway"].

The review article assigns TRAPPC11 to mammalian TRAPP III context and states that TRAPP III contains core TRAPP plus TRAPPC8, TRAPPC11, TRAPPC12, and TRAPPC13 PMID:27066478. It also cautions that TRAPP tethering remains inconclusive PMID:27066478.

Reactome models TRAPPC complexes II and III as complex-level RAB1 GEFs in anterograde ER-to-ERGIC/Golgi traffic and macroautophagy context [Reactome:R-HSA-8877475 "RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III"]. For TRAPPC11, this supports contributes_to RAB1 GEF activity in TRAPPIII/TRAPP context rather than independent GEF activity.

The secretory-screen paper provides independent support that human Gryzun/C4orf41 is a secretory pathway component and that RNAi of human Gryzun blocks Golgi exit PMID:19942856.

The glycosylation/CDG paper is cached as abstract-only. It supports Golgi/secretory context and TRAPPIII membership, but I am not using it to infer a separate glycosylation GO annotation PMID:27862579.

Proteostasis-network context: the PN entry flags TRAPPIII/autophagophore recruitment as relevant context. Falcon completed successfully and identified accessible primary evidence that TRAPPC11 variants affect autophagic flux and autophagosome sealing. PMID:31575891 reports that only the compound heterozygous subject displayed an autophagic flux defect, that LC3-II could not be cleared during starvation, and that fibroblasts lacking full-length TRAPPC11 failed to seal isolation membranes into autophagosomes [PMID:31575891 "displayed an autophagic flux defect"; PMID:31575891 "LC3-II could not be cleared from the cells over the time course of starvation examined"; PMID:31575891 "failed to seal isolation membranes into autophagosomes"]. Therefore, add a direct TRAPPC11 autophagosome maturation annotation while keeping ER-to-ERGIC/Golgi trafficking and TRAPP complex stability as the main shared TRAPP functions.

Falcon deep research was requested with just deep-research-falcon human TRAPPC11 and completed successfully in 563.63 seconds, producing TRAPPC11-deep-research-falcon.md.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

Moved out of the YAML description: the prior wording framed TRAPPC11 in the Proteostasis Network TRAPPIII context and emphasized TRAPPIII/TRAPP complex membership, complex-level RAB1 GEF activity, ER-to-Golgi transport, TRAPP complex stability, and autophagosome maturation.

Pn Notes

(TRAPPC11-pn-notes.md)

TRAPPC11 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q7Z392
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/TRAPPC11/TRAPPC11-ai-review.yaml
AIGR review HTML: present - genes/human/TRAPPC11/TRAPPC11-ai-review.html
Gene notes: present - genes/human/TRAPPC11/TRAPPC11-notes.md
GOA TSV: present - genes/human/TRAPPC11/TRAPPC11-goa.tsv
UniProt record: present - genes/human/TRAPPC11/TRAPPC11-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/TRAPPC11.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/TRAPPC11.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/TRAPPC11/TRAPPC11-deep-research-falcon.md

AIGR Review Snapshot

Description: TRAPPC11 (C4orf41/Gryzun) is a metazoan TRAPP/TRAPPIII-associated subunit. It stabilizes mammalian TRAPP architecture and contributes to early secretory pathway trafficking between the ER, ERGIC, and Golgi. Patient-cell evidence also supports a TRAPPC11 role in starvation-induced autophagic flux and autophagosome sealing. As a TRAPPIII-associated subunit, TRAPPC11 is connected to TRAPP complex membership, complex-level RAB1 GEF activity, ER-to-Golgi transport, TRAPP complex stability, and autophagosome maturation.
Existing/core annotation action counts: ACCEPT: 10; KEEP_AS_NON_CORE: 1; MARK_AS_OVER_ANNOTATED: 1; MODIFY: 2; NEW: 1

PN Consistency Summary

Consistency: Consistent, with the review going beyond PN. Falcon deep research (the only one of the six that completed) plus notes and YAML agree on TRAPPIII membership + early-secretory ER/ERGIC/Golgi traffic + TRAPP-stability, AND add a direct autophagy role from PMID:31575891 (patient fibroblasts fail autophagic flux / fail to seal isolation membranes). No contradictions; the review supplements the PN complex-only mapping with a gene-specific autophagy BP.
PN story / NEW pressure: PN restricts to GO:0030008 membership, but TRAPPC11 has direct human autophagy evidence the PN node does not project. Review adds GO:0097352 autophagosome maturation as NEW (verified real via OLS; absent from GOA, confirmed). Caveat (verified): GO:0097352's definition is "removal of PI3P/Atg8-LC3 after phagophore closure" (a disassembly step), whereas PMID:31575891 describes a failure to seal/close isolation membranes — which maps more naturally to GO:0000045 autophagosome assembly. The NEW term direction is defensible but slightly off the cited mechanism. Conclude: ADD an autophagy BP (defensible), but reconsider GO:0097352 vs GO:0000045 for the sealing/closure phenotype.
Evidence alignment: Overlap on TRAPP: PN cites PMID:27066478 + Frontiers review = review core. Review enriches with PMID:21525244 (TRAPP identification), 19942856 (Golgi-exit screen), 27862579 (CDG), and 31575891 (autophagy, PN does not list).
Verdict: Consistent; one substantive curation question. Recommended edits: in TRAPPC11-ai-review.yaml, reconsider the NEW GO:0097352 autophagosome maturation against GO:0000045 autophagosome assembly, since PMID:31575891 evidence concerns isolation-membrane sealing/closure, not the post-closure PI3P/LC3-removal step GO:0097352 defines.

Full Consistency Review

UniProt: Q7Z392 (C4orf41/Gryzun) · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: Autophagy-Lysosome Pathway → Autophagophore initiation and elongation → Autophagy component recruitment to autophagophore → TRAPP complex component (1 row, ALP) ; PN-node mapping: leaf type=mapped/ok_for_propagation→GO:0030008 TRAPP complex; group=no_mapping; class=context_only/too_broad→GO:0016236 macroautophagy; branch=no_mapping. Projects GO:0030008 (already_in_goa_exact).
Consistency: Consistent, with the review going beyond PN. Falcon deep research (the only one of the six that completed) plus notes and YAML agree on TRAPPIII membership + early-secretory ER/ERGIC/Golgi traffic + TRAPP-stability, AND add a direct autophagy role from PMID:31575891 (patient fibroblasts fail autophagic flux / fail to seal isolation membranes). No contradictions; the review supplements the PN complex-only mapping with a gene-specific autophagy BP.
PN story / NEW pressure: PN restricts to GO:0030008 membership, but TRAPPC11 has direct human autophagy evidence the PN node does not project. Review adds GO:0097352 autophagosome maturation as NEW (verified real via OLS; absent from GOA, confirmed). Caveat (verified): GO:0097352's definition is "removal of PI3P/Atg8-LC3 after phagophore closure" (a disassembly step), whereas PMID:31575891 describes a failure to seal/close isolation membranes — which maps more naturally to GO:0000045 autophagosome assembly. The NEW term direction is defensible but slightly off the cited mechanism. Conclude: ADD an autophagy BP (defensible), but reconsider GO:0097352 vs GO:0000045 for the sealing/closure phenotype.
Mapping strategy: Gene does not change the TRAPP node (GO:0030008 correct). The autophagy addition is gene-specific and correctly NOT propagated from the shared TRAPP bucket.
Evidence alignment: Overlap on TRAPP: PN cites PMID:27066478 + Frontiers review = review core. Review enriches with PMID:21525244 (TRAPP identification), 19942856 (Golgi-exit screen), 27862579 (CDG), and 31575891 (autophagy, PN does not list).
Verdict: Consistent; one substantive curation question. Recommended edits: in TRAPPC11-ai-review.yaml, reconsider the NEW GO:0097352 autophagosome maturation against GO:0000045 autophagosome assembly, since PMID:31575891 evidence concerns isolation-membrane sealing/closure, not the post-closure PI3P/LC3-removal step GO:0097352 defines.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/TRAPPC11/TRAPPC11-ai-review.yaml
PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Autophagy component recruitment to autophagophore | TRAPP complex component

UniProt: Q7Z392
In branches: ALP
Notes: TRAPP III complex, specific subunit. The TRAPP complex serves as a GEF for RAB1. Involved in ATG9 and ATG2 trafficking
PN references (titles):
- Membrane Trafficking in Autophagy - ScienceDirect
- Frontiers | TRAPP Complexes in Secretion and Autophagy | Cell and Developmental Biology (frontiersin.org)
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0030008 TRAPP complex]
  rationale: This PN leaf is a curated component bucket for TRAPP subunits used in autophagophore recruitment. The matching GO cellular-component term is TRAPP complex, and the member genes already converge strongly on that assignment in existing GOA.
- [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

GO:0030008 TRAPP complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q7Z392
gene_symbol: TRAPPC11
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TRAPPC11 (C4orf41/Gryzun) is a metazoan TRAPP/TRAPPIII-associated subunit. It stabilizes mammalian
  TRAPP architecture and contributes to early secretory pathway trafficking between the ER, ERGIC, and
  Golgi. Patient-cell evidence also supports a TRAPPC11 role in starvation-induced autophagic flux and
  autophagosome sealing. As a TRAPPIII-associated subunit, TRAPPC11 is connected to TRAPP complex
  membership, complex-level RAB1 GEF activity, ER-to-Golgi transport, TRAPP complex stability, and
  autophagosome maturation.
alternative_products:
- name: '1'
  id: Q7Z392-1
- name: '2'
  id: Q7Z392-2
  sequence_note: VSP_035095, VSP_035098, VSP_035099
- name: '3'
  id: Q7Z392-3
  sequence_note: VSP_035098, VSP_035099
- name: '4'
  id: Q7Z392-4
  sequence_note: VSP_035096, VSP_035097
existing_annotations:
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology.
    action: ACCEPT
    reason: Accept as a supported cellular location. UniProt maps TRAPPC11 to the Golgi
      apparatus with PMID:27862579 support, and the CDG abstract reports delayed Golgi
      vesicular transport caused by TRAPPC11 mutation.
    additional_reference_ids:
    - PMID:27862579
    - file:human/TRAPPC11/TRAPPC11-uniprot.txt
    - PMID:21525244
    supported_by:
    - &id015
      reference_id: file:human/TRAPPC11/TRAPPC11-uniprot.txt
      supporting_text: Golgi apparatus {ECO:0000269|PubMed:27862579}
    - &id006
      reference_id: PMID:27862579
      supporting_text: delayed vesicular transport in the GA due to mutations in
        TRAPPC11, a subunit of the TRAPPIII complex
    - &id010
      reference_id: PMID:21525244
      supporting_text: RNAi against C8, C11, or C12 resulted in Golgi fragmentation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: located_in
  review:
    summary: Cytoplasm is a broad but reasonable location for soluble/peripheral TRAPP
      complex biology.
    action: ACCEPT
    reason: Accept as a broad supported location/context. TRAPP subunits have large
      soluble pools and function on early secretory pathway membranes; the more specific
      cytosol/Golgi locations are captured elsewhere.
    additional_reference_ids:
    - PMID:21525244
    - Reactome:R-HSA-8877475
    supported_by:
    - &id016
      reference_id: PMID:21525244
      supporting_text: Localization of subunits by fluorescence microscopy has proven
        difficult due to the large soluble pools of the proteins
    - &id001
      reference_id: PMID:21525244
      supporting_text: TRAPP functions either at ER exit sites or at peripheral ERGIC
        (BFA-resistant) elements
    - &id017
      reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 nucleotide exchange is stimulated in these pathways by the
        GEF activity of the multisubunit TRAPPC complexes II and III
- term:
    id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport
      through TRAPP/TRAPPIII.
    action: ACCEPT
    reason: Accept as a core process. TRAPPC11 was identified as a mammalian TRAPP
      component with C11-specific ER-to-ERGIC traffic evidence, and independent
      secretory-screen evidence shows human Gryzun/C4orf41 knockdown blocks Golgi exit.
    additional_reference_ids:
    - PMID:21525244
    - PMID:19942856
    - PMID:27066478
    - Reactome:R-HSA-8877475
    - file:human/TRAPPC11/TRAPPC11-uniprot.txt
    supported_by:
    - &id002
      reference_id: PMID:21525244
      supporting_text: Specifically, we implicate C11 in membrane traffic between the ER
        and the ERGIC compartment
    - &id009
      reference_id: PMID:21525244
      supporting_text: knockdowns of either C11 or C12 arrest a cargo protein in a
        BFA-resistant compartment
    - *id001
    - &id003
      reference_id: PMID:19942856
      supporting_text: RNAi of human Gryzun (C4orf41) blocks Golgi exit
    - &id007
      reference_id: file:human/TRAPPC11/TRAPPC11-uniprot.txt
      supporting_text: Involved in endoplasmic reticulum to Golgi apparatus
    - &id004
      reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 is involved in COPII-mediated anterograde traffic from the
        endoplasmic reticulum to the ERGIC
- term:
    id: GO:0048208
    label: COPII vesicle coat assembly
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: The COPII coat assembly annotation captures early secretory context but
      overstates TRAPPC11 as a coat-assembly factor.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC11 evidence supports
      early ER/ERGIC/Golgi trafficking in COPII-associated anterograde traffic, not
      assembly of the COPII vesicle coat.
    proposed_replacement_terms:
    - &id005
      id: GO:0006888
      label: endoplasmic reticulum to Golgi vesicle-mediated transport
    additional_reference_ids:
    - PMID:21525244
    - PMID:19942856
    - Reactome:R-HSA-8877475
    supported_by:
    - *id002
    - *id001
    - *id003
    - *id004
- term:
    id: GO:0099022
    label: obsolete vesicle tethering
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: The obsolete vesicle-tethering annotation should not be retained as-is.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported
      TRAPPC11/TRAPP process. Mammalian TRAPP tethering remains unresolved and this GO
      term is obsolete.
    proposed_replacement_terms:
    - *id005
    additional_reference_ids:
    - PMID:27066478
    - PMID:21525244
    - PMID:19942856
    supported_by:
    - reference_id: PMID:27066478
      supporting_text: evidence that any TRAPP complex acts as a membrane tether is
        currently inconclusive
    - *id002
    - *id001
    - *id003
- term:
    id: GO:1990072
    label: TRAPPIII protein complex
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: part_of
  review:
    summary: TRAPPC11 is modeled as a mammalian TRAPPIII-associated subunit.
    action: ACCEPT
    reason: Accept as core complex membership. TRAPPC11 is a metazoan TRAPP component
      assigned to mammalian TRAPP III in the review literature and independently
      described as a TRAPPIII subunit in the TRAPPC11-CDG abstract.
    additional_reference_ids:
    - PMID:27066478
    - PMID:27862579
    - PMID:21525244
    - Reactome:R-HSA-8877475
    supported_by:
    - &id018
      reference_id: PMID:27066478
      supporting_text: TRAPP III, which contains core TRAPP plus TrappC8, 11-13
    - reference_id: PMID:27066478
      supporting_text: TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP
        III, which contains core TRAPP plus TrappC8, 11-13
    - *id006
    - &id008
      reference_id: PMID:21525244
      supporting_text: C4orf41 and TTC-15 interact both with each other and with
        previously characterized TRAPP subunits
    - reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 and the TRAPPCIII complex play a role in the formation of
        the pre-autophagosomal structure (PAS)
- term:
    id: GO:0045054
    label: constitutive secretory pathway
  evidence_type: IMP
  original_reference_id: PMID:19942856
  qualifier: involved_in
  review:
    summary: TRAPPC11 is directly supported as an early secretory pathway factor.
    action: ACCEPT
    reason: Accept as a supported core process at broad pathway level. The RNAi
      secretory screen shows human C4orf41/Gryzun blocks Golgi exit, and the TRAPP
      component paper places TRAPPC11 in early ER/ERGIC/Golgi trafficking.
    additional_reference_ids:
    - PMID:19942856
    - PMID:21525244
    - file:human/TRAPPC11/TRAPPC11-uniprot.txt
    supported_by:
    - *id003
    - *id002
    - &id011
      reference_id: PMID:21525244
      supporting_text: These results imply that the three novel TRAPP-associated
        proteins function in the early secretory pathway
    - *id007
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21525244
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC11 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. The interaction evidence is better represented as
      TRAPP/TRAPPIII complex membership and TRAPP architecture/stability, not a generic
      protein binding molecular function.
    additional_reference_ids:
    - PMID:21525244
    - PMID:27066478
    supported_by:
    - *id008
    - &id012
      reference_id: PMID:21525244
      supporting_text: These results firmly establish the newly identified proteins as
        stable TRAPP interactors
    - &id013
      reference_id: PMID:21525244
      supporting_text: we report two novel TRAPP proteins, C4orf41/Gryzun (now
        designated TRAPPC11) and TTC-15 (now designated TRAPPC12)
    - &id014
      reference_id: PMID:27066478
      supporting_text: TrappC11, which is distantly related to Trs130/TrappC10, and
        TrappC12, were identified based on their co-fractionation with TRAPP and effect
        of their depletion on ER-to-Golgi transport
- term:
    id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: involved_in
  review:
    summary: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport
      through TRAPP/TRAPPIII.
    action: ACCEPT
    reason: Accept as a core process. TRAPPC11 was identified as a mammalian TRAPP
      component with C11-specific ER-to-ERGIC traffic evidence, and independent
      secretory-screen evidence shows human Gryzun/C4orf41 knockdown blocks Golgi exit.
    additional_reference_ids:
    - PMID:21525244
    - PMID:19942856
    - PMID:27066478
    - Reactome:R-HSA-8877475
    - file:human/TRAPPC11/TRAPPC11-uniprot.txt
    supported_by:
    - *id002
    - *id009
    - *id001
    - *id003
    - *id007
    - *id004
- term:
    id: GO:0007030
    label: Golgi organization
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: involved_in
  review:
    summary: Golgi organization is a direct TRAPPC11-depletion phenotype but is
      secondary to early secretory trafficking.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. Golgi fragmentation is a useful readout of TRAPPC11/TRAPP
      disruption, while the core process is ER-to-ERGIC/Golgi trafficking and TRAPP
      complex stability.
    additional_reference_ids:
    - PMID:21525244
    supported_by:
    - *id010
    - *id011
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: part_of
  review:
    summary: TRAPPC11 is a mammalian TRAPP complex component.
    action: ACCEPT
    reason: Accept as core cellular-component membership. TAP purification and
      coimmunoprecipitation identify C4orf41/TRAPPC11 as stably associated with
      mammalian TRAPP subunits.
    additional_reference_ids:
    - PMID:21525244
    - PMID:27066478
    - file:human/TRAPPC11/TRAPPC11-uniprot.txt
    supported_by:
    - *id008
    - *id012
    - *id013
    - *id014
    - reference_id: file:human/TRAPPC11/TRAPPC11-uniprot.txt
      supporting_text: Component of the multisubunit TRAPP (transport protein
- term:
    id: GO:0061635
    label: regulation of protein complex stability
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: involved_in
  review:
    summary: TRAPPC11 supports mammalian TRAPP complex stability.
    action: ACCEPT
    reason: Accept as a supported core process/function of TRAPPC11 within the TRAPP
      complex. C11 depletion partially disassembles the complex and the authors conclude
      that C11 stabilizes mammalian TRAPP.
    additional_reference_ids:
    - PMID:21525244
    supported_by:
    - &id019
      reference_id: PMID:21525244
      supporting_text: depletion of C11 (Supplemental Figure 5) resulted in a partial
        disassembly of the TRAPP complex
    - &id020
      reference_id: PMID:21525244
      supporting_text: this protein stabilizes the TRAPP complex in mammalian cells
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:27862579
  qualifier: located_in
  review:
    summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology.
    action: ACCEPT
    reason: Accept as a supported cellular location. UniProt maps TRAPPC11 to the Golgi
      apparatus with PMID:27862579 support, and the CDG abstract reports delayed Golgi
      vesicular transport caused by TRAPPC11 mutation.
    additional_reference_ids:
    - PMID:27862579
    - file:human/TRAPPC11/TRAPPC11-uniprot.txt
    - PMID:21525244
    supported_by:
    - *id015
    - *id006
    - *id010
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8877475
  qualifier: located_in
  review:
    summary: Cytosol is consistent with TRAPPC11 as a soluble/peripheral TRAPP
      trafficking subunit.
    action: ACCEPT
    reason: Accept as a supported location/context for TRAPPC11-containing TRAPP
      reactions. The complex is modeled as a cytosolic/peripheral trafficking GEF
      recruited to early secretory membranes.
    additional_reference_ids:
    - PMID:21525244
    - Reactome:R-HSA-8877475
    supported_by:
    - *id016
    - *id017
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IMP
  original_reference_id: PMID:31575891
  qualifier: involved_in
  review:
    summary: TRAPPC11 supports autophagosome maturation/sealing in a variant-dependent
      mammalian cell context.
    action: NEW
    reason: Add as a new direct process annotation. Patient fibroblasts with
      TRAPPC11 variants show defective starvation-induced autophagic flux, poor
      LC3/LAMP1 colocalization, and failure to seal isolation membranes into
      autophagosomes; this is more specific than a generic autophagy row for the
      accessible evidence.
    additional_reference_ids:
    - file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md
    supported_by:
    - &id021
      reference_id: PMID:31575891
      supporting_text: displayed an autophagic flux defect
    - &id022
      reference_id: PMID:31575891
      supporting_text: LC3-II could not be cleared from the cells over the time course
        of starvation examined
    - &id023
      reference_id: PMID:31575891
      supporting_text: poor starvation-dependent co-localization
    - &id024
      reference_id: PMID:31575891
      supporting_text: failed to seal isolation membranes into autophagosomes
    - &id025
      reference_id: PMID:31575891
      supporting_text: the extreme carboxy-terminus of TRAPPC11, but not residue
        Gly980, is critical for starvation-induced autophagy
    - reference_id: file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md
      supporting_text: defective starvation-induced autophagic flux
references:
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: PMID:19942856
  title: A genome-wide RNA interference screen identifies two novel components of the
    metazoan secretory pathway.
  findings: []
- id: PMID:21525244
  title: C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage
    in ER-to-Golgi trafficking.
  findings: []
- id: PMID:27066478
  title: TRAPP Complexes in Secretion and Autophagy.
  findings: []
- id: PMID:27862579
  title: Mutations in TRAPPC11 are associated with a congenital disorder of
    glycosylation.
  findings: []
- id: PMID:31575891
  title: Characterization of three TRAPPC11 variants suggests a critical role for the
    extreme carboxy terminus of the protein.
  findings: []
- id: Reactome:R-HSA-8877475
  title: TRAPPC complexes exchange GTP for GDP on RAB1
  findings: []
- id: file:human/TRAPPC11/TRAPPC11-uniprot.txt
  title: UniProtKB record for TRAPPC11
  findings: []
- id: file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md
  title: Falcon deep research report for TRAPPC11
  findings: []
core_functions:
- contributes_to_molecular_function:
    id: GO:0005085
    label: guanyl-nucleotide exchange factor activity
  in_complex:
    id: GO:1990072
    label: TRAPPIII protein complex
  description: TRAPPC11 contributes a metazoan TRAPP/TRAPPIII-associated subunit needed
    for stable TRAPP architecture, early secretory pathway traffic between ER, ERGIC,
    and Golgi, and autophagosome maturation/sealing in variant-sensitive mammalian cell
    contexts. It should be modeled as contributing to complex-level TRAPP/RAB1 GEF
    activity and TRAPP stability rather than independently enabling GEF activity or
    COPII coat assembly.
  directly_involved_in:
  - id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  - id: GO:0045054
    label: constitutive secretory pathway
  - id: GO:0061635
    label: regulation of protein complex stability
  - id: GO:0097352
    label: autophagosome maturation
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005794
    label: Golgi apparatus
  supported_by:
  - *id017
  - *id018
  - *id008
  - *id012
  - *id002
  - *id009
  - *id001
  - *id003
  - *id019
  - *id020
  - *id015
  - *id021
  - *id022
  - *id024
proposed_new_terms: []
suggested_questions:
- question: Should human TRAPPC11 be curated specifically as a TRAPPIII subunit rather
    than only as a generic TRAPP complex component?
  experts:
  - ComplexPortal curators
  - Reactome TRAPP curators
  - GO cellular component editors
- question: Should human TRAPPC11 be curated specifically to autophagosome maturation
    based on variant-cell autophagosome sealing assays, or should this remain a
    broader macroautophagy/autophagy annotation in GOA?
  experts:
  - GO autophagy editors
  - TRAPP/autophagy researchers
- question: Should COPII coat assembly and obsolete tethering annotations on TRAPP
    subunits be systematically replaced by ER-to-Golgi vesicle-mediated transport when
    coat assembly or tethering is not directly shown?
  experts:
  - GO transport editors
  - Reactome TRAPP curators
suggested_experiments:
- description: Rescue TRAPPC11-depleted cells with wild-type and disease-associated
    TRAPPC11 variants, then measure VSV-G ER-to-ERGIC/Golgi transport, Golgi morphology,
    and TRAPP complex assembly by native fractionation.
  experiment_type: secretory cargo rescue and complex stability assay
  hypothesis: TRAPPC11 supports early secretory transport by stabilizing mammalian
    TRAPP/TRAPPIII architecture.
- description: Reconstitute TRAPPC11-containing TRAPPIII and measure RAB1 GDP-to-GTP
    exchange with and without TRAPPC11 depletion or mutant replacement.
  experiment_type: complex reconstitution and RAB1 GEF assay
  hypothesis: TRAPPC11 contributes to complex-level TRAPPIII/RAB1 GEF function through
    assembly or stabilization rather than acting as an independent GEF.
- description: Test TRAPPC11 knockdown/rescue and C-terminal disease variants in
    starvation-induced LC3-II clearance, LC3/LAMP1 colocalization, and protease
    protection assays alongside ER-Golgi cargo transport.
  experiment_type: parallel autophagosome maturation and secretion assay
  hypothesis: TRAPPC11 C-terminal integrity is required for autophagosome maturation or
    sealing and can be separated experimentally from some ER-Golgi transport defects.

TRAPPC11

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Human TRAPPC11 (UniProt Q7Z392; gene TRAPPC11; synonym C4orf41)—functional annotation

1) Identity verification and key definitions (current understanding)

2) Molecular function, pathways, and subcellular localization (evidence-based)

2.1 Primary cellular role: early secretory pathway trafficking (ER → ERGIC → Golgi)

2.2 Complex membership and Rab pathway assignment (Rab1-centric TRAPPIII)

2.3 Glycosylation: TRAPPC11-linked hypoglycosylation in disease and models

2.4 Autophagy: role in autophagosome maturation/sealing

3) Recent developments (prioritizing 2023–2024)

3.1 Updated TRAPP complex models (composition, Rab specificity, and membrane context)

3.2 2023 cohort expansion and quantitative phenotyping of TRAPPC11 disease

3.3 2024 review-level consolidation: variant landscape and cellular readouts

4) Current applications and real-world implementations

4.1 Diagnostic genetics for TRAPPC11-related disorders

4.2 Cellular assays as functional implementation (research and variant interpretation)

5) Expert synthesis and analysis (authoritative interpretations)

Visual evidence (TRAPP model including TRAPPC11)

Summary table (evidence-based functional annotation)

Key takeaways

Artifacts

Citations

📚 Additional Documentation

Notes

TRAPPC11 review notes

Description cleanup note

Pn Notes

TRAPPC11 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Autophagy component recruitment to autophagophore | TRAPP complex component

Projected GO annotations (1)

Note

📄 View Raw YAML