C. elegans Ciliopathy Project - Curation Recommendations

Summary

Total Genes Reviewed: 20
Total Annotations: 477
ACCEPT (Publication-Ready): 368
Changes Recommended: 109

Summary Table

Gene	Priority	Total	ACCEPT	MODIFY	REMOVE	NEW	Other	Changes
daf-19	P1	17	13	1	0	1	2	4 🟡
osm-3	P1	47	38	4	0	0	5	9 🔴
osm-5	P1	23	18	0	1	0	4	5 🔴
che-2	P1	21	11	1	0	1	8	10 🔴
che-3	P1	33	25	1	2	0	5	8 🔴
bbs-1	P1	22	17	1	3	0	1	5 🔴
bbs-8	P1	28	22	3	0	1	2	6 🔴
mks-3	P1	10	6	0	0	4	0	4 🟡
nphp-1	P2	17	12	2	0	0	3	5 🔴
nphp-4	P2	30	20	1	0	0	9	10 🔴
mks-1	P2	6	2	1	0	2	1	4 🟡
mks-5	P2	24	20	0	0	1	3	4 🟡
mks-6	P2	11	11	0	0	0	0	0 ✅
mksr-2	P2	17	9	3	0	0	5	8 🔴
bbs-2	P3	20	14	2	0	3	1	6 🔴
bbs-5	P3	17	14	1	0	0	2	3 🟡
bbs-7	P3	24	20	2	0	0	2	4 🟡
lov-1	P3	30	25	5	0	0	0	5 🔴
pkd-2	P3	60	60	0	0	0	0	0 ✅
pef-1	P3	20	11	1	2	3	3	9 🔴

Status Key

• ✅ Publication-Ready: All annotations ACCEPT (no changes needed)
• 🟡 Review-Ready: 1-4 changes needed (minor consolidation)
• 🔴 Implementation-Needed: 5+ changes needed (systematic review required)

Gene-by-Gene Curation Recommendations

DAF-19 🟡

Total Annotations: 17 | Changes: 4

MODIFY: GO:0010468 - regulation of gene expression

• Evidence: IMP
• Issue: While accurate, this annotation is quite general. DAF-19's primary role is as a transcriptional activator of ciliary gene expression. A more specific
• Proposed: GO:0045724 - positive regulation of cilium assembly

KEEP_AS_NON_CORE: GO:0050829 - defense response to Gram-negative bacterium

• Evidence: IMP
• Issue: This is a legitimate function of DAF-19 supported by experimental evidence, but it represents a secondary/pleiotropic role rather than its core functi

KEEP_AS_NON_CORE: GO:0042427 - serotonin biosynthetic process

• Evidence: IMP
• Issue: This annotation reflects DAF-19's role in regulating serotonin biosynthesis through transcriptional control of tph-1. However, this is a secondary fun

NEW: GO:0045724 - positive regulation of cilium assembly

• Evidence: IMP
• Issue: This annotation is strongly supported by the literature and represents DAF-19's central role in ciliogenesis. This biological process annotation captu

OSM-3 🔴

Total Annotations: 47 | Changes: 9

MODIFY: GO:0030030 - cell projection organization

• Evidence: IBA
• Issue: While technically accurate, this term is too general. OSM-3 has a specific role in cilium organization, not cell projections broadly.
• Proposed: GO:0060271 - cilium assembly
• Proposed: GO:1905515 - non-motile cilium assembly

MODIFY: GO:0005815 - microtubule organizing center

• Evidence: IBA
• Issue: While basal bodies are MTOCs, the more precise term for OSM-3 localization is ciliary basal body, which is experimentally validated.
• Proposed: GO:0036064 - ciliary basal body

MARK_AS_OVER_ANNOTATED: GO:0098971 - anterograde dendritic transport of neurotransmitter receptor complex

• Evidence: IBA
• Issue: This function is established for mammalian KIF17 but not demonstrated for C. elegans OSM-3. OSM-3 is specifically involved in ciliary transport, not g

MODIFY: GO:0007018 - microtubule-based movement

• Evidence: IEA
• Issue: While accurate, a more specific term exists for OSM-3's biological process.
• Proposed: GO:0035720 - intraciliary anterograde transport

MODIFY: GO:0032991 - protein-containing complex

• Evidence: IEA
• Issue: Too general. OSM-3 specifically forms kinesin complexes.
• Proposed: GO:0005871 - kinesin complex

UNDECIDED: GO:1902856 - negative regulation of non-motile cilium assembly

• Evidence: IGI
• Issue: The relationship between OSM-3 and negative regulation of cilium assembly is indirect and context-dependent (dyf-5 mutant background). OSM-3 primarily

KEEP_AS_NON_CORE: GO:0061066 - positive regulation of dauer larval development

• Evidence: IMP
• Issue: Dauer phenotype is secondary to ciliary defects. OSM-3 mutants have defective sensory cilia which impairs pheromone sensing required for dauer decisio

KEEP_AS_NON_CORE: GO:0043053 - dauer entry

• Evidence: IGI
• Issue: Dauer phenotype is secondary to ciliary defects. OSM-3's role in dauer is indirect through its effects on sensory cilia function.

MARK_AS_OVER_ANNOTATED: GO:0046626 - regulation of insulin receptor signaling pathway

• Evidence: IGI
• Issue: The connection to insulin signaling is indirect. OSM-3 mutations cause ciliary defects that affect sensory neuron function. Sensory neurons in turn re

OSM-5 🔴

Total Annotations: 23 | Changes: 5

KEEP_AS_NON_CORE: GO:0006970 - response to osmotic stress

• Evidence: IMP
• Issue: The osmotic avoidance defect is a downstream consequence of defective sensory cilia, not a direct molecular function of OSM-5. The gene name "osm" der

KEEP_AS_NON_CORE: GO:0035641 - locomotory exploration behavior

• Evidence: IMP
• Issue: Exploration behavior is influenced by sensory input from ciliated neurons. The behavioral defect in osm-5 mutants is secondary to ciliary dysfunction,

KEEP_AS_NON_CORE: GO:0050921 - positive regulation of chemotaxis

• Evidence: IMP
• Issue: The chemotaxis defect in osm-5 mutants results from defective sensory cilia that cannot properly detect chemical signals. OSM-5 does not directly regu

KEEP_AS_NON_CORE: GO:0043053 - dauer entry

• Evidence: IGI
• Issue: Dauer entry requires functional chemosensory cilia to detect pheromone signals. osm-5 mutants fail to form dauers properly because they cannot sense t

REMOVE: GO:0003674 - molecular_function

• Evidence: ND
• Issue: This ND annotation is outdated. OSM-5 has established molecular functions including its role as an IFT-B structural component and kinesin binding. The

CHE-2 🔴

Total Annotations: 21 | Changes: 10

MODIFY: GO:0042073 - intraciliary transport

• Evidence: NAS
• Issue: The annotation is correct but could be more specific. CHE-2/IFT80 is primarily involved in anterograde transport as part of the IFT-B complex. Conside
• Proposed: GO:0035720 - intraciliary anterograde transport

KEEP_AS_NON_CORE: GO:0090325 - regulation of locomotion involved in locomotory behavior

• Evidence: IGI
• Issue: This is a downstream consequence of cilium structure defects rather than a direct function of CHE-2. The effect on locomotion is indirect, mediated th

KEEP_AS_NON_CORE: GO:0090326 - positive regulation of locomotion involved in locomotory behavior

• Evidence: IMP
• Issue: Pleiotropic effect of cilium defects. CHE-2's primary role is in cilium assembly and IFT; the locomotory phenotype is an indirect consequence of senso

KEEP_AS_NON_CORE: GO:0040014 - regulation of multicellular organism growth

• Evidence: IGI
• Issue: Secondary phenotype resulting from defective sensory cilia. The primary function of CHE-2 is cilium assembly, not growth regulation per se.

KEEP_AS_NON_CORE: GO:0040018 - positive regulation of multicellular organism growth

• Evidence: IMP
• Issue: Indirect effect of cilium structure defects on sensory-mediated growth regulation. Not a direct molecular function of CHE-2.

KEEP_AS_NON_CORE: GO:0006935 - chemotaxis

• Evidence: IMP
• Issue: Chemotaxis defect is a consequence of abnormal cilium structure in sensory neurons. CHE-2 enables chemotaxis indirectly by being required for proper c

KEEP_AS_NON_CORE: GO:0040024 - dauer larval development

• Evidence: IGI
• Issue: Dauer development phenotype is secondary to cilium structure defects. che-2 mutants affect dauer formation because sensory cilia are required for envi

MARK_AS_OVER_ANNOTATED: GO:0030512 - negative regulation of transforming growth factor beta receptor signaling pathway

• Evidence: IGI
• Issue: This is an indirect effect mediated through cilium structure defects affecting sensory perception of environmental cues that regulate TGF-beta signali

KEEP_AS_NON_CORE: GO:0006935 - chemotaxis

• Evidence: IMP
• Issue: Chemotaxis defect is downstream of cilium structure defect. CHE-2 is required for cilium assembly in chemosensory neurons; without proper cilia, these

NEW: GO:0035720 - intraciliary anterograde transport

• Evidence: IBA
• Issue: More specific than GO:0042073 (intraciliary transport). IFT-B is specifically the anterograde transport machinery while IFT-A is retrograde. This term

CHE-3 🔴

Total Annotations: 33 | Changes: 8

REMOVE: GO:0060294 - cilium movement involved in cell motility

• Evidence: IBA
• Issue: C. elegans sensory cilia are non-motile primary cilia-like structures (PMID:10790327). CHE-3 functions in retrograde IFT, not in ciliary motility. Thi

REMOVE: GO:0097729 - 9+2 motile cilium

• Evidence: IBA
• Issue: CHE-3 is localized to non-motile sensory cilia in C. elegans (PMID:10790327). The annotation to 9+2 motile cilium is incorrect for this species. The I

KEEP_AS_NON_CORE: GO:0050793 - regulation of developmental process

• Evidence: IEA
• Issue: The annotation is not incorrect but represents downstream phenotypic effects rather than core function. CHE-3's role in development is indirect, media

KEEP_AS_NON_CORE: GO:0043053 - dauer entry

• Evidence: IGI
• Issue: The annotation reflects real genetic data but represents an indirect effect of ciliary defects on chemosensory-dependent dauer signaling (PMID:1732156

KEEP_AS_NON_CORE: GO:0061066 - positive regulation of dauer larval development

• Evidence: IMP
• Issue: The phenotype is real but represents an indirect consequence of ciliary defects disrupting chemosensory signaling required for normal dauer induction.

MARK_AS_OVER_ANNOTATED: GO:0030512 - negative regulation of transforming growth factor beta receptor signaling pathway

• Evidence: IGI
• Issue: The genetic interaction is real but the annotation implies a more direct role in TGF-beta signaling than warranted. CHE-3's effect on TGF-beta signali

MODIFY: GO:0008104 - intracellular protein localization

• Evidence: IMP
• Issue: While not incorrect, the term is too general. CHE-3's role is specifically in retrograde IFT, which is a specialized form of intracellular transport.
• Proposed: GO:0035721 - intraciliary retrograde transport

KEEP_AS_NON_CORE: GO:0007635 - chemosensory behavior

• Evidence: IMP
• Issue: The phenotype is well-documented but represents an indirect consequence of ciliary defects. CHE-3 does not directly participate in chemosensory signal

BBS-1 🔴

Total Annotations: 22 | Changes: 5

MODIFY: GO:0005813 - centrosome

• Evidence: IBA
• Issue: In C. elegans, BBS-1 localizes predominantly to the ciliary base/basal body rather than a classical centrosome structure. The more accurate term would
• Proposed: GO:0036064 - ciliary basal body

REMOVE: GO:0005113 - patched binding

• Evidence: IBA
• Issue: C. elegans lacks Smoothened and canonical Hedgehog signaling. While C. elegans has Patched homologs (PTC-1, PTC-3), these have diverged functionally a

REMOVE: GO:0005119 - smoothened binding

• Evidence: IBA
• Issue: C. elegans lacks Smoothened entirely - the gene is absent from the genome. This is a well-documented evolutionary divergence of the Hedgehog signaling

REMOVE: GO:0003674 - molecular_function

• Evidence: ND
• Issue: This ND annotation is outdated. The gene now has IBA molecular function annotations (though the patched/smoothened binding ones are not valid for C. e

KEEP_AS_NON_CORE: GO:0043005 - neuron projection

• Evidence: IDA
• Issue: While technically correct that BBS-1 localizes to neuronal projections (specifically ciliated dendrites of sensory neurons), the more informative anno

BBS-8 🔴

Total Annotations: 28 | Changes: 6

MODIFY: GO:0015031 - protein transport

• Evidence: IEA
• Issue: Correct but overly general. BBS-8 specifically functions in ciliary protein transport via IFT. A more specific term would better capture the actual fu
• Proposed: GO:0042073 - intraciliary transport

MODIFY: GO:0030030 - cell projection organization

• Evidence: IEA
• Issue: Overly general. The more specific term "cilium assembly" (GO:0060271) or "non-motile cilium assembly" (GO:1905515) would be more appropriate and is al
• Proposed: GO:0060271 - cilium assembly

MODIFY: GO:1904107 - protein localization to microvillus membrane

• Evidence: IMP
• Issue: The finger compartment of AFD neurons contains microvilli-like protrusions, but these are functionally a specialized ciliary signaling compartment. Th
• Proposed: GO:0061512 - protein localization to cilium

KEEP_AS_NON_CORE: GO:0008355 - olfactory learning

• Evidence: IMP
• Issue: This is a downstream phenotype rather than a direct function. BBS genes are required for AWC(ON) neuron function, and defects in this neuron lead to i

KEEP_AS_NON_CORE: GO:0006935 - chemotaxis

• Evidence: IMP
• Issue: This is a downstream phenotype resulting from ciliary sensory defects, not a direct molecular function of BBS-8. Chemotaxis defects are a consequence

NEW: GO:0060090 - molecular adaptor activity

• Evidence: ISS
• Issue: This molecular function annotation is proposed based on the structural role of BBS-8 within the BBSome. The protein contains 7-8 TPR repeats (UniProt)

MKS-3 🟡

Total Annotations: 10 | Changes: 4

NEW: GO:1905349 - ciliary transition zone assembly

• Evidence: IGI
• Issue: This annotation captures the role of MKS-3 in transition zone organization, which is distinct from but related to its localization there. The TEM stud

NEW: GO:1903565 - negative regulation of protein localization to cilium

• Evidence: IMP
• Issue: This is a critical annotation capturing the ciliary gate function of MKS-3. The paper directly demonstrates that TZ proteins including those in the MK

NEW: GO:0007635 - chemosensory behavior

• Evidence: IMP
• Issue: This annotation captures the physiological/behavioral consequence of MKS-3 function in sensory cilia. The osmotic avoidance assay tests chemosensory b

NEW: GO:0005198 - structural molecule activity

• Evidence: IDA
• Issue: This molecular function annotation captures MKS-3's role as a structural component of the MKS complex. Evidence shows MKS-3 is part of the TZ architec

NPHP-1 🔴

Total Annotations: 17 | Changes: 5

KEEP_AS_NON_CORE: GO:0005737 - cytoplasm

• Evidence: IBA
• Issue: The annotation is not incorrect but does not represent the core localization of NPHP-1. The protein's critical function is at the transition zone. Cyt

UNDECIDED: GO:0090251 - protein localization involved in establishment of planar polarity

• Evidence: IBA
• Issue: While this may be a conserved function based on phylogenetic analysis, there is no direct experimental evidence for a role in planar polarity in C. el

MODIFY: GO:0036064 - ciliary basal body

• Evidence: IDA
• Issue: In C. elegans, the basal body and transition zone are distinct regions. Multiple detailed studies using GFP-tagged NPHP-1 show specific localization t
• Proposed: GO:0035869 - ciliary transition zone

KEEP_AS_NON_CORE: GO:0008340 - determination of adult lifespan

• Evidence: IMP
• Issue: This is a pleiotropic phenotype likely resulting from disrupted ciliary function affecting sensory signaling pathways that regulate lifespan (insulin/

MODIFY: GO:0008104 - intracellular protein localization

• Evidence: IGI
• Issue: This annotation is too general. NPHP-1 specifically functions at the TZ to regulate ciliary access of IFT components and other proteins. A more specif
• Proposed: GO:0035721 - intraciliary transport involved in cilium assembly

NPHP-4 🔴

Total Annotations: 30 | Changes: 10

KEEP_AS_NON_CORE: GO:0090090 - negative regulation of canonical Wnt signaling pathway

• Evidence: IBA
• Issue: While human NPHP4 has been linked to Wnt signaling regulation and TZ proteins can modulate ciliary signaling, the core function of C. elegans NPHP-4 i

MARK_AS_OVER_ANNOTATED: GO:0005856 - cytoskeleton

• Evidence: IEA
• Issue: While technically not wrong (cilia are cytoskeletal structures), this is too broad and uninformative. The more specific ciliary component annotations

KEEP_AS_NON_CORE: GO:0090090 - negative regulation of canonical Wnt signaling pathway

• Evidence: IEA
• Issue: Duplicate annotation by different method. The Wnt signaling role is likely secondary to core ciliary gating function.

KEEP_AS_NON_CORE: GO:0016358 - dendrite development

• Evidence: IGI
• Issue: The primary function is in cilia, but dendrite development is affected in double mutants with MKS module genes, likely as a secondary consequence of T

KEEP_AS_NON_CORE: GO:0023041 - neuronal signal transduction

• Evidence: IC
• Issue: While NPHP-4 is required for sensory neuron function, the primary defect is in ciliary structure/gating rather than direct signal transduction. The be

KEEP_AS_NON_CORE: GO:0034606 - response to hermaphrodite contact

• Evidence: IGI
• Issue: Behavioral phenotype that reflects ciliary sensory function rather than core molecular function. Important for understanding organismal role but secon

KEEP_AS_NON_CORE: GO:0034607 - turning behavior involved in mating

• Evidence: IGI
• Issue: Male-specific sensory behavior dependent on ciliary function. Secondary phenotype reflecting ciliary gating defects.

KEEP_AS_NON_CORE: GO:0008340 - determination of adult lifespan

• Evidence: IMP
• Issue: Pleiotropic phenotype that may result from altered ciliary signaling. Not a core function of NPHP-4 but represents downstream physiological consequenc

MODIFY: GO:0008104 - intracellular protein localization

• Evidence: IGI
• Issue: This is too broad. The annotation should more specifically reflect the role in regulating ciliary access and localization of specific IFT components.
• Proposed: GO:0072638 - intraciliary transport
• Proposed: GO:1904491 - protein localization to ciliary transition zone

KEEP_AS_NON_CORE: GO:0035177 - larval foraging behavior

• Evidence: IMP
• Issue: Behavioral phenotype reflecting sensory function. The foraging defect is likely due to chemosensory impairment from ciliary dysfunction rather than a

MKS-1 🟡

Total Annotations: 6 | Changes: 4

MODIFY: GO:0005929 - cilium

• Evidence: IEA
• Issue: The annotation is not incorrect since the transition zone is part of the cilium, but it is too general. MKS-1 specifically localizes to the ciliary tr
• Proposed: GO:0035869 - ciliary transition zone

MARK_AS_OVER_ANNOTATED: GO:0030030 - cell projection organization

• Evidence: IEA
• Issue: This term is too general. The more specific GO:0060271 (cilium assembly) annotation is already present and better captures the actual function of MKS-

NEW: GO:0035869 - ciliary transition zone

• Evidence: IDA
• Issue: Multiple publications directly demonstrate that MKS-1 localizes to the transition zone in C. elegans sensory neurons. This is a core annotation that a

NEW: GO:1905349 - ciliary transition zone assembly

• Evidence: IMP
• Issue: MKS-1 contributes to transition zone assembly as part of the MKS module. The function is only revealed in combination with NPHP mutations due to redun

MKS-5 🟡

Total Annotations: 24 | Changes: 4

MARK_AS_OVER_ANNOTATED: GO:0005856 - cytoskeleton

• Evidence: IEA
• Issue: While cilia are cytoskeleton-related structures, this annotation is overly broad and uninformative. The specific localization to the ciliary transitio

MARK_AS_OVER_ANNOTATED: GO:0030030 - cell projection organization

• Evidence: IEA
• Issue: This IEA based on UniProt keyword mapping is too broad. The specific terms GO:0060271 (cilium assembly) and GO:1905515 (non-motile cilium assembly) be

KEEP_AS_NON_CORE: GO:0006935 - chemotaxis

• Evidence: IMP
• Issue: Chemotaxis is a downstream phenotype of ciliary dysfunction rather than a direct molecular function of MKS-5. The chemosensory defects arise as a cons

NEW: GO:0060090 - molecular adaptor activity

• Evidence: IMP
• Issue: This molecular function annotation is supported by extensive evidence from multiple studies. Williams et al. 2011 established MKS-5 as a central compo

MKSR-2 🔴

Total Annotations: 17 | Changes: 8

MODIFY: GO:0060271 - cilium assembly

• Evidence: IBA
• Issue: While MKSR-2 is involved in cilium assembly, the annotation should be more specific. In C. elegans sensory neurons, these are non-motile primary cilia
• Proposed: GO:1905515 - non-motile cilium assembly

MODIFY: GO:0005929 - cilium

• Evidence: IEA
• Issue: MKSR-2 specifically localizes to the ciliary transition zone, not the cilium proper. The IEA annotation is too broad. The protein is found at the base
• Proposed: GO:0035869 - ciliary transition zone

MARK_AS_OVER_ANNOTATED: GO:0005515 - protein binding

• Evidence: IPI
• Issue: The term 'protein binding' (GO:0005515) is too generic and uninformative per GO curation guidelines. The interaction with MKSR-1 is biologically relev

MARK_AS_OVER_ANNOTATED: GO:0005515 - protein binding

• Evidence: IPI
• Issue: Same as above - 'protein binding' is too generic. The interaction data is valid but better captured by the MKS complex component annotation.

KEEP_AS_NON_CORE: GO:0008340 - determination of adult lifespan

• Evidence: IGI
• Issue: This is a secondary phenotype arising from ciliary dysfunction rather than a direct core function of MKSR-2. The lifespan extension in mutants results

MARK_AS_OVER_ANNOTATED: GO:0005515 - protein binding

• Evidence: IPI
• Issue: Same issue as other protein binding annotations - the term is too generic. The interaction with MKS-1 is biologically meaningful (they form the B9/MKS

MODIFY: GO:0008104 - intracellular protein localization

• Evidence: IMP
• Issue: This term is too generic. MKSR-2 specifically functions in localizing proteins to the ciliary transition zone. The more specific term GO:1904491 (prot
• Proposed: GO:1904491 - protein localization to ciliary transition zone

KEEP_AS_NON_CORE: GO:0035177 - larval foraging behavior

• Evidence: IGI
• Issue: Foraging behavior defects are a downstream consequence of sensory cilium dysfunction. C. elegans uses ciliated sensory neurons for chemosensation, whi

BBS-2 🔴

Total Annotations: 20 | Changes: 6

MARK_AS_OVER_ANNOTATED: GO:0016020 - membrane

• Evidence: IBA
• Issue: While the BBSome is involved in membrane protein trafficking to cilia, this generic 'membrane' annotation is too broad to be informative. The protein

MODIFY: GO:0031514 - motile cilium

• Evidence: IBA
• Issue: C. elegans cilia are sensory (non-motile) cilia, not motile cilia. The organism lacks motile cilia entirely - its sensory neurons have non-motile cili
• Proposed: GO:0097730 - non-motile cilium

MODIFY: GO:0015031 - protein transport

• Evidence: IEA
• Issue: While BBS-2 is involved in protein transport, this term is too general. The BBSome specifically functions in ciliary protein trafficking - sorting mem
• Proposed: GO:0042073 - intraciliary transport

NEW: GO:0042073 - intraciliary transport

• Evidence: IDA
• Issue: This is a core function annotation that should be added. PMID:22922713 provides definitive evidence that the BBSome controls IFT assembly and turnarou

NEW: GO:0035735 - intraciliary transport involved in cilium assembly

• Evidence: IMP
• Issue: This annotation links the BBSome's IFT function directly to cilium assembly. PMID:22922713 demonstrates that disruption of BBSome-IFT coupling leads t

NEW: GO:0005198 - structural molecule activity

• Evidence: IDA
• Issue: BBS-2 is a core structural component of the BBSome complex. PMID:22922713 demonstrates that BBS proteins form a complex using BiFC assays. The BBSome

BBS-5 🟡

Total Annotations: 17 | Changes: 3

MODIFY: GO:0015031 - protein transport

• Evidence: IEA
• Issue: While protein transport is accurate, a more specific term reflecting the ciliary transport function would be more informative. The annotation should b
• Proposed: GO:0035735 - intraciliary transport involved in cilium assembly
• Proposed: GO:0042073 - intraciliary transport

KEEP_AS_NON_CORE: GO:0030030 - cell projection organization

• Evidence: IEA
• Issue: This is a general parent term of cilium assembly. While not incorrect, it is less informative than the specific cilium assembly annotation. Keeping as

UNDECIDED: GO:0034451 - centriolar satellite

• Evidence: IEA
• Issue: While human BBS5 localizes to centriolar satellites, it is unclear if this is a significant localization for C. elegans BBS-5. The UniProt record note

BBS-7 🟡

Total Annotations: 24 | Changes: 4

MODIFY: GO:0008104 - intracellular protein localization

• Evidence: IBA
• Issue: While the annotation captures BBS-7's role in protein localization, this term is too general. The more specific function is ciliary protein localizati
• Proposed: GO:0061512 - protein localization to cilium

MODIFY: GO:0016020 - membrane

• Evidence: IBA
• Issue: The term 'membrane' is too general for BBS-7 localization. BBS-7 specifically localizes to the ciliary membrane system and is involved in ciliary memb
• Proposed: GO:0005929 - cilium

KEEP_AS_NON_CORE: GO:1904107 - protein localization to microvillus membrane

• Evidence: IMP
• Issue: This is a specialized function in AFD thermosensory neurons rather than a core function. While experimentally validated, it represents a specific neur

KEEP_AS_NON_CORE: GO:0006935 - chemotaxis

• Evidence: IMP
• Issue: Secondary phenotype. Chemotaxis defects are a consequence of ciliary dysfunction rather than a direct molecular function of BBS-7. BBS-7's core functi

LOV-1 🔴

Total Annotations: 30 | Changes: 5

MODIFY: GO:0005262 - calcium channel activity

• Evidence: IBA
• Issue: LOV-1 is a PC1-family member that partners with the TRPP channel PKD-2. The channel activity likely resides primarily in PKD-2, while LOV-1 functions
• Proposed: GO:0015276 - ligand-gated ion channel activity

MODIFY: GO:0070588 - calcium ion transmembrane transport

• Evidence: IEA
• Issue: LOV-1 is part of a receptor-channel complex with PKD-2. The transport activity is more directly attributable to PKD-2. LOV-1's role is as a receptor/r
• Proposed: GO:0010959 - regulation of metal ion transport

MODIFY: GO:0005515 - protein binding

• Evidence: IPI
• Issue: The generic "protein binding" annotation is uninformative. LOV-1 interacts with ATP-2 via its PLAT domain, which should be captured with a more specif
• Proposed: GO:0019904 - protein domain specific binding

MODIFY: GO:0005515 - protein binding

• Evidence: IPI
• Issue: Generic "protein binding" is uninformative. The interaction with KIN-10 (casein kinase II regulatory subunit) is through the LOV-1 C-terminus. A more
• Proposed: GO:0019904 - protein domain specific binding

MODIFY: GO:0005515 - protein binding

• Evidence: IPI
• Issue: This is a less informative duplicate of the protein domain specific binding annotation (GO:0019904) from the same reference. The interaction with STAM
• Proposed: GO:0019904 - protein domain specific binding

PEF-1 🔴

Total Annotations: 20 | Changes: 9

REMOVE: GO:0005634 - nucleus

• Evidence: IBA
• Issue: No experimental evidence supports nuclear localization of PEF-1 in C. elegans. Both PMID:11312268 and PMID:39550471 show exclusive membrane/ciliary lo

KEEP_AS_NON_CORE: GO:0005829 - cytosol

• Evidence: IBA
• Issue: While membrane association is the predominant localization, some cytosolic presence may occur during protein synthesis/transport. However, the core fu

REMOVE: GO:0005506 - iron ion binding

• Evidence: IEA
• Issue: This is likely an incorrect inference. PPEF family phosphatases use manganese as the catalytic metal ion. UniProt annotation and experimental evidence

MARK_AS_OVER_ANNOTATED: GO:0016787 - hydrolase activity

• Evidence: IEA
• Issue: This is too general to be informative. The more specific GO:0004722 (protein serine/threonine phosphatase activity) already captures the molecular fun

MARK_AS_OVER_ANNOTATED: GO:0046872 - metal ion binding

• Evidence: IEA
• Issue: This is too general to be informative. The more specific GO:0030145 (manganese ion binding) and GO:0005509 (calcium ion binding) already capture the s

MODIFY: GO:0050906 - detection of stimulus involved in sensory perception

• Evidence: IEA
• Issue: While PEF-1 is involved in sensory processes, it is not a receptor that directly detects stimuli. Rather, it modulates sensory signaling in cilia. Mor
• Proposed: GO:0040040 - thermosensory behavior
• Proposed: GO:0050906 - detection of stimulus involved in sensory perception

NEW: GO:0005930 - axoneme

• Evidence: IDA
• Issue: Experimental evidence from PMID:39550471 demonstrates specific axonemal localization within cilia. This should be added as a new annotation with IDA e

NEW: GO:0097730 - non-motile cilium

• Evidence: IDA
• Issue: PEF-1 is specifically localized to non-motile sensory cilia in C. elegans. This is more specific than the generic cilium term.

NEW: GO:0040040 - thermosensory behavior

• Evidence: IMP
• Issue: Experimental mutant phenotype demonstrates PEF-1 function in thermosensory behavior. AFD neuron expression supports this role.

Overall Statistics

By Priority

Priority 1 (Core IFT)
- Annotations: 201 | Accept: 150 (74%) | Changes: 51

Priority 2 (Transition Zone)
- Annotations: 105 | Accept: 74 (70%) | Changes: 31

Priority 3 (BBSome/PKD)
- Annotations: 171 | Accept: 144 (84%) | Changes: 27

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Document generated from ciliopathy gene reviews