G patch domain-containing protein 11 (also CCDC75; historically nicknamed CENP-Y), a member of the GPATCH family of glycine-rich G-patch motif proteins that cooperate with DEAH-box RNA helicases to remodel ribonucleoprotein complexes during pre-mRNA splicing. GPATCH11 localizes diffusely in the nucleoplasm with additional signal at the centrosome and acts as a regulator of pre-mRNA splicing; the Schizosaccharomyces pombe ortholog Sap34 binds U2 snRNP and U4/U6·U5 tri-snRNP components and interacts with the DEAH-box helicase Prp43 through its G-patch domain, suggesting regulation of Prp43 activity in early spliceosomes; loss of Sap34 causes a global splicing defect with increased intron retention. Biallelic loss-of-function variants in human GPATCH11 (notably the recurrent c.328+1G>T splice variant, which removes the G-patch domain) cause a syndrome of early-onset retinal dystrophy with neurological impairment and craniofacial/skeletal features, with mouse and patient-derived data implicating mis-splicing, altered primary-cilium-associated gene expression, and impaired photoreceptor function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000776 kinetochore | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA propagated from the single IDA in PMID:20813266. The upstream GO curators have flagged this annotation (geneontology/go-annotation#6450) as incorrect because the only experimental source is a low-resolution image from a large-scale mitotic-chromosome proteomic screen, and the dedicated 2024 patient/mouse study (PMID:39572588) explicitly reports nucleoplasmic and centrosomal localization with no kinetochore signal. The S. pombe ortholog Sap34 (PMID:42260140) is a spliceosome-associated protein interacting with U2 and tri-snRNP components, not a kinetochore protein. Notably, the current PAINT curation of PTHR21032 (snapshot 2026-02-25, interpro/panther/PTHR21032/PTHR21032-paint.tsv) no longer carries a kinetochore IBD at node PTN000471210 - it now asserts nucleoplasm (GO:0005654), centrosome (GO:0005813) and RNA splicing (GO:0008380) there instead - so this 2017 IBA row is stale and should disappear from GOA as the re-curation flows through. Reason: Propagated by PAINT from a disputed IDA; the IBA inherits the same over-annotation problem. Functional evidence across human, mouse, and fission yeast converges on a pre-mRNA splicing role, not a kinetochore role. The 2026-02-25 PAINT re-curation of PTHR21032 has already withdrawn the kinetochore assertion at PTN000471210, confirming this GOA row (dated 2017-02-28) is a stale propagation awaiting refresh. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: SOURCE EVIDENCE WEAK Sources checked: PANTHER:PTN000471210 · GPATCH11 family ancestral node (Eukaryota) SOURCE STALE OR MISSING The current PAINT curation of PTHR21032 (snapshot 2026-02-25) carries no kinetochore IBD at this node; it asserts nucleoplasm (GO:0005654), centrosome (GO:0005813) and RNA splicing (GO:0008380) instead, so the transferred term no longer appears on the source record. UniProtKB:Q8N954 · GPATCH11 (the target's own IDA, PMID:20813266) SOURCE BAD The target appearing in its own WITH/FROM is expected for IBA; the problem here is that the seed IDA itself - a single low-resolution GFP image from a ~4,000-protein mitotic-chromosome screen - is contradicted by dedicated microscopy (PMID:39572588) and flagged upstream in geneontology/go-annotation#6450. Proposed replacements: nucleoplasm centrosome Supporting Evidence: PMID:39572588 a subcellular localization of GPATCH11 characterized by a diffuse presence in the nucleoplasm, as well as centrosomal localization PMID:42260140 Sap34 forms a complex with components of the U2 small nuclear ribonucleoprotein (snRNP) and the U4/U6 × U5 tri-snRNP, which are required for early spliceosome assembly and activation file:human/GPATCH11/GPATCH11-deep-research-falcon.md GPATCH11 localizes exclusively to centrosomes with no detectable localization at kinetochores or centromeres |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-derived IEA from the G-patch domain (IPR000467). The G-patch motif is a well-established RNA-binding/helicase-cofactor module, so this annotation is correct in spirit but very general. The patient/mouse study (PMID:39572588) and the S. pombe ortholog characterization (PMID:42260140) both implicate GPATCH11/Sap34 in pre-mRNA binding and spliceosome remodeling. The known ligand of the G-patch module is RNA (not DNA), so the more specific child term RNA binding (GO:0003723) captures the same evidence more informatively. Reason: Domain-based IEA from G-patch (IPR000467); biologically consistent with the protein's spliceosomal role but broader than the evidence warrants. The G-patch motif is an RNA-binding/DEAH-helicase-cofactor module (GPATCH proteins carry "multiple RNA-binding motifs" per PMID:39572588), and all functional evidence for GPATCH11 concerns RNA metabolism, so GO:0003723 (RNA binding) is the appropriate level of specificity; there is no evidence for DNA binding that would justify the broader nucleic acid binding term. Proposed replacements: RNA binding Supporting Evidence: PMID:39572588 G-patch domain-containing (GPATCH) proteins form a distinct group characterized by a glycine-rich motif and multiple RNA-binding motifs file:human/GPATCH11/GPATCH11-deep-research-falcon.md is predicted to act as a cofactor for DEAH-box RNA helicases, which are ATP-dependent enzymes involved in RNA remodeling |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: IntAct annotation derived from large-scale interactome mapping (Rolland et al. 2014) with partners SDCBP (O00560) and ADGRB3 (O60242). Per project guidance, "protein binding" is uninformative and these interactors are not mechanistically linked to GPATCH11's spliceosomal function. Keep the interaction-level evidence but mark non-core. Reason: Generic protein-binding term with no functional specificity; partners are from high-throughput Y2H/AP-MS, not from the splicing literature. |
| GO:0000776 kinetochore | IDA PMID:20813266 The protein composition of mitotic chromosomes determined us... | MARK AS OVER ANNOTATED | Summary: Source of the disputed kinetochore call (geneontology/go-annotation#6450). PMID:20813266 is a multi-classifier proteomic screen of purified mitotic chromosomes that nicknamed GPATCH11 "CENP-Y" based on a single low-resolution GFP image among ~4,000 candidate proteins. The 2024 patient/mouse study (PMID:39572588) directly examined GPATCH11 localization and reports diffuse nucleoplasm plus centrosome, with no kinetochore signal, and the GPATCH/ spliceosome literature (including the S. pombe ortholog, PMID:42260140) has not confirmed a kinetochore role. The upstream curator who filed go-annotation#6450 explicitly recommends correction. Per CLAUDE.md, prefer MARK_AS_OVER_ANNOTATED rather than silent REMOVE for an experimentally supported call; flag the over-annotation and propose the localization terms that the high-resolution study actually supports. Reason: Based on a low-resolution image in a high-throughput screen; later dedicated microscopy and patient data show nucleoplasmic + centrosomal localization without kinetochore signal. GO curators have flagged the annotation upstream. Proposed replacements: nucleoplasm centrosome Supporting Evidence: PMID:39572588 a subcellular localization of GPATCH11 characterized by a diffuse presence in the nucleoplasm, as well as centrosomal localization, suggesting potential functions in RNA and cilia metabolism file:human/GPATCH11/GPATCH11-deep-research-falcon.md GPATCH11 localizes exclusively to centrosomes with no detectable localization at kinetochores or centromeres |
| GO:0005654 nucleoplasm | IDA PMID:39572588 GPATCH11 variants cause mis-splicing and early-onset retinal... | NEW | Summary: Proposed new annotation based on dedicated localization study showing diffuse nucleoplasmic signal in patient and control fibroblasts and in mouse retina, replacing the disputed kinetochore call. Reason: High-resolution microscopy in the 2024 study directly supports nucleoplasmic localization for GPATCH11. Supporting Evidence: PMID:39572588 a subcellular localization of GPATCH11 characterized by a diffuse presence in the nucleoplasm, as well as centrosomal localization |
| GO:0005813 centrosome | IDA PMID:39572588 GPATCH11 variants cause mis-splicing and early-onset retinal... | NEW | Summary: Proposed new annotation based on dedicated localization study showing centrosomal signal alongside nucleoplasmic signal in patient/control fibroblasts and mouse retina. Reason: High-resolution microscopy in the 2024 study directly supports centrosomal localization for GPATCH11, consistent with the patient cilium-related phenotype. Supporting Evidence: PMID:39572588 a subcellular localization of GPATCH11 characterized by a diffuse presence in the nucleoplasm, as well as centrosomal localization |
| GO:0000398 mRNA splicing, via spliceosome | ISO PMID:42260140 GPATCH11 ortholog Sap34 regulates pre-mRNA splicing by inter... | NEW | Summary: Proposed new annotation supported by orthologous evidence from the S. pombe Sap34 study, which demonstrates a direct role in pre-mRNA splicing via U2 snRNP and tri-snRNP interactions, and by retinal transcriptomic / proteomic data from the human/mouse GPATCH11 study showing splicing dysregulation upon loss of function. Reason: Convergent evidence from the S. pombe ortholog (PMID:42260140) and patient/mouse omics (PMID:39572588) supports a core role in pre-mRNA splicing via the spliceosome. Supporting Evidence: PMID:42260140 deletion of sap34 leads to a global reduction in splicing efficiency, predominantly associated with increased intron retention PMID:39572588 Proteomic analysis of mouse retina confirms the roles GPATCH11 plays in RNA processing, splicing, and transcription regulation file:human/GPATCH11/GPATCH11-deep-research-falcon.md Transcriptomic analysis of retinas from Gpatch11-mutant mice revealed 299 altered splicing events affecting 178 genes |
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Download this section (compressed HTML)Q: Does human GPATCH11 directly bind and activate a specific human DEAH-box helicase (e.g., DHX15, the human Prp43 ortholog), analogous to Sap34→Prp43 in fission yeast?
Q: Is the centrosomal pool of GPATCH11 mechanistically tied to primary cilium assembly/function, or does it reflect a regulatory role for splicing of cilium-related transcripts?
Q: Which GPATCH11-dependent splicing events drive the photoreceptor and neurological phenotypes seen in the c.328+1G>T patient cohort?
Experiment: Co-IP / cross-linking MS in human cells to map the GPATCH11 interactome against U2 snRNP, tri-snRNP and DHX15, mirroring the Sap34 study in S. pombe.
Experiment: High-resolution immunofluorescence and live-cell imaging of endogenously tagged GPATCH11 across mitotic stages to directly test for any kinetochore pool, settling the open IBA/IDA call.
Experiment: Long-read RNA-seq of GPATCH11-depleted human retinal organoids or patient-derived photoreceptor cultures to define the splicing programs affected by loss of function.
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