KIAA1614 is a 1190-amino-acid human protein with a DUF4685 domain and extensive predicted disordered regions. It belongs to the PANTHER Par6-related family, but lacks annotated canonical PB1, CRIB and PDZ domains. Nuclear crosslinking proteomics detected an association with histone H2B, and an affinity-purification study detected association with PTPRR. These observations identify candidate cellular contexts without establishing a molecular mechanism. Its role in cell polarity or centrosome function remains unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0060341 regulation of cellular localization | IBA GO_REF:0000033 | UNDECIDED | Summary: Reassess the ancestral assignment using target architecture and node placement; absence of a human assay is not a refutation. Reason: The broad regulation-of-localization claim may be retained through a noncanonical mechanism; missing canonical Par6 domains does not itself refute the process. The historic PTN001019968 assertion is not present in the current family IBD slice, which is a version difference rather than proof of loss. Live InterPro confirms a DUF4685 domain and a PTHR14102/IPR051741 family match, not a separately detected PAR6 domain. The missing annotated PB1/CRIB/PDZ architecture is a substantive reason to examine functional divergence, but no family alignment or tree reconstruction establishes loss of this particular function. The existing OpenScientist report is incorporated critically: short k-mer similarity, low AlphaFold confidence and absence from interaction databases do not prove nonhomology, absent binding or absent process participation. Keep uncertainty pending assessment of the relevant conserved region and ancestral node, rather than requiring a new experiment for every inherited function. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001019968 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. RGD:1303273 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. Supporting Evidence: file:human/KIAA1614/KIAA1614-hypotheses/kgap-kiaa1614-par6-polarity-scaffold/openscientist.md the exact basis for grouping KIAA1614 with Par6 cannot be fully evaluated without the underlying HMM profile alignment |
| GO:0007163 establishment or maintenance of cell polarity | IBA GO_REF:0000033 | UNDECIDED | Summary: Reassess the ancestral assignment using target architecture and node placement; absence of a human assay is not a refutation. Reason: Current PAINT places the polarity IBD at PTN001019969 and propagates it to target leaf PTN002554625; the older source row names PTN001019968. Neither version is a pairwise similarity transfer. Live InterPro confirms a DUF4685 domain and a PTHR14102/IPR051741 family match, not a separately detected PAR6 domain. The missing annotated PB1/CRIB/PDZ architecture is a substantive reason to examine functional divergence, but no family alignment or tree reconstruction establishes loss of this particular function. The existing OpenScientist report is incorporated critically: short k-mer similarity, low AlphaFold confidence and absence from interaction databases do not prove nonhomology, absent binding or absent process participation. Keep uncertainty pending assessment of the relevant conserved region and ancestral node, rather than requiring a new experiment for every inherited function. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001019968 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. UniProtKB:Q9NPB6 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. Supporting Evidence: file:human/KIAA1614/KIAA1614-hypotheses/kgap-kiaa1614-par6-polarity-scaffold/openscientist.md the exact basis for grouping KIAA1614 with Par6 cannot be fully evaluated without the underlying HMM profile alignment |
| GO:0005938 cell cortex | IBA GO_REF:0000033 | UNDECIDED | Summary: Reassess the ancestral assignment using target architecture and node placement; absence of a human assay is not a refutation. Reason: Current PAINT retains a cortex assertion for the target through PTN001019969; no target-specific exclusion assay was found. Nuclear crosslinking does not exclude a cortical pool. Live InterPro confirms a DUF4685 domain and a PTHR14102/IPR051741 family match, not a separately detected PAR6 domain. The missing annotated PB1/CRIB/PDZ architecture is a substantive reason to examine functional divergence, but no family alignment or tree reconstruction establishes loss of this particular function. The existing OpenScientist report is incorporated critically: short k-mer similarity, low AlphaFold confidence and absence from interaction databases do not prove nonhomology, absent binding or absent process participation. Keep uncertainty pending assessment of the relevant conserved region and ancestral node, rather than requiring a new experiment for every inherited function. Propagation Review Root cause: UNRESOLVED Sources checked: MGI:MGI:1927223 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. MGI:MGI:2135605 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. PANTHER:PTN001019968 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. Supporting Evidence: file:human/KIAA1614/KIAA1614-hypotheses/kgap-kiaa1614-par6-polarity-scaffold/openscientist.md the exact basis for grouping KIAA1614 with Par6 cannot be fully evaluated without the underlying HMM profile alignment |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: The nuclear IBA is corroborated by an independently curated human nuclear crosslinking observation. Reason: IntAct interaction IM-26653-2713 (EBI-20924026) maps human KIAA1614 Q5VZ46 to histone H2B Q93079 by crosslinking in PMID:30021884. The primary abstract and cached discussion describe intact-nucleus crosslinking followed by fractionation; this provides target-specific corroboration of the nuclear IBA. It is high-throughput proximity/association evidence, not a validated nuclear mechanism or exclusive localization. The cached full-text extraction lacks the methods/results sections, and the raw peptide identifications were not reanalyzed. A reported P-body association does not contradict a nuclear pool. The ancestral placement at PTN001019968 is therefore compatible with the available target evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001019968 SUPPORTS TRANSFER Verified ancestral nuclear IBD and current target descent; independently curated nuclear crosslinking corroborates the target location. Supporting Evidence: PMID:30021884 The crosslinking of intact nuclei coupled with sequential detergent fractionation file:human/KIAA1614/KIAA1614-hypotheses/kgap-kiaa1614-par6-polarity-scaffold/openscientist.md Detected by crosslinking mass spectrometry in intact human nuclei (PMID 30021884). |
| GO:0016324 apical plasma membrane | IBA GO_REF:0000033 | UNDECIDED | Summary: Reassess the ancestral assignment using target architecture and node placement; absence of a human assay is not a refutation. Reason: The current apical-membrane IBA descends from PTN001019968. Neither absence of a transmembrane helix nor a nuclear association excludes peripheral or transient membrane localization. Live InterPro confirms a DUF4685 domain and a PTHR14102/IPR051741 family match, not a separately detected PAR6 domain. The missing annotated PB1/CRIB/PDZ architecture is a substantive reason to examine functional divergence, but no family alignment or tree reconstruction establishes loss of this particular function. The existing OpenScientist report is incorporated critically: short k-mer similarity, low AlphaFold confidence and absence from interaction databases do not prove nonhomology, absent binding or absent process participation. Keep uncertainty pending assessment of the relevant conserved region and ancestral node, rather than requiring a new experiment for every inherited function. Propagation Review Root cause: UNRESOLVED Sources checked: MGI:MGI:2135605 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. PANTHER:PTN001019968 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. ZFIN:ZDB-GENE-010319-35 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. ZFIN:ZDB-GENE-050923-1 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. ZFIN:ZDB-GENE-070705-215 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. ZFIN:ZDB-GENE-090312-133 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. Supporting Evidence: file:human/KIAA1614/KIAA1614-hypotheses/kgap-kiaa1614-par6-polarity-scaffold/openscientist.md the exact basis for grouping KIAA1614 with Par6 cannot be fully evaluated without the underlying HMM profile alignment |
| GO:0007098 centrosome cycle | IBA GO_REF:0000033 | UNDECIDED | Summary: Reassess the ancestral assignment using target architecture and node placement; absence of a human assay is not a refutation. Reason: The source Q9NPB6 is PARD6A, not PARD6B. Current PAINT places this IBD at PTN001019969. KIAA1614 could contribute to centrosome regulation without reproducing every canonical Par6 interaction. Live InterPro confirms a DUF4685 domain and a PTHR14102/IPR051741 family match, not a separately detected PAR6 domain. The missing annotated PB1/CRIB/PDZ architecture is a substantive reason to examine functional divergence, but no family alignment or tree reconstruction establishes loss of this particular function. The existing OpenScientist report is incorporated critically: short k-mer similarity, low AlphaFold confidence and absence from interaction databases do not prove nonhomology, absent binding or absent process participation. Keep uncertainty pending assessment of the relevant conserved region and ancestral node, rather than requiring a new experiment for every inherited function. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001019969 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. UniProtKB:Q9NPB6 UNRESOLVED Historic GOA source identifier preserved. Current PAINT IBD and target rows were inspected; whether the inherited function is retained in the divergent KIAA1614 architecture remains unresolved, not disproved by donor count or absence of target assays. Supporting Evidence: file:human/KIAA1614/KIAA1614-hypotheses/kgap-kiaa1614-par6-polarity-scaffold/openscientist.md the exact basis for grouping KIAA1614 with Par6 cannot be fully evaluated without the underlying HMM profile alignment |
Loading supporting content…
Download this section (compressed HTML)Q: Which sequence region supports KIAA1614 placement relative to canonical PARD6 proteins, and do the functions asserted at PTN001019968/PTN001019969 extend to its noncanonical architecture?
Q: Does the nuclear histone crosslink reflect stable KIAA1614 chromatin association, and how does this relate to any cortical, membrane or P-body pool?
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: KIAA1614 has no established direct molecular mechanism or validated functional partner set.
OPEN BIOLOGYCURATION MF_DARK
What is known: DUF4685 and the Par6-related family assignment coexist with noncanonical domain architecture. Nuclear H2B crosslinking and PTPRR affinity association are experimentally detected leads, not defined biochemical functions.
Significance: All current process and localization annotations rest on phylogenetic/domain inference. Without a direct molecular activity or partner set, KIAA1614 remains function-unknown despite several plausible Par6-related hypotheses.
What would resolve it: Affinity/proximity proteomics, co-IP against Par3/Par6/aPKC and other polarity factors, DUF4685/PAR6_homolog domain-deletion rescue, and structural/biochemical assays for conserved binding surfaces.
Provenance (the field's own admissions):
Gap: The distribution, dynamics and functional relevance of KIAA1614 cellular pools remain incompletely characterized.
OPEN BIOLOGYCURATION CC_DARK
What is known: A nuclear pool is supported by an IntAct-curated histone crosslink from an intact-nucleus study. Cortex and apical-membrane IBA assignments remain unresolved; these sites and a reported P-body association need not be mutually exclusive.
Significance: Distinguishing stable residency from transient association would connect location to a molecular mechanism.
What would resolve it: Endogenous tagging or validated-antibody imaging in polarized epithelial and retinal cell contexts, with orthogonal fractionation and perturbation of candidate domain determinants.
Provenance (the field's own admissions):
Gap: KIAA1614 has no validated pathway or biological-process assignment.
OPEN BIOLOGYCURATION BP_DARK
What is known: The family IBD assertions are meaningful evolutionary evidence, but divergent annotated architecture leaves retention of particular polarity/centrosome roles unresolved. The uncertainty is not solely the lack of a KIAA1614 experiment.
Significance: This is the process-level consequence of the MF and CC gaps: the gene cannot be confidently placed in a pathway until its molecular partners and site of action are known.
What would resolve it: CRISPR perturbation and rescue in relevant cells, assaying epithelial polarity, junctional integrity, centrosome-cycle phenotypes, and any phenotype tied to validated KIAA1614 interaction partners.
Provenance (the field's own admissions):
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)