GJC2

UniProt ID: Q5T442
Organism: Homo sapiens
Review Status: COMPLETE
Aliases:
GJA12 CX47 CX46.6 SPG44
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Gene Description

GJC2 encodes connexin-47, a four-pass membrane protein that forms gap junction channels. Oligodendrocyte connexin-47 pairs with astrocyte connexin-43 across opposing cells, supporting intercellular ion and small-solute transfer. Pathogenic variants cause hypomyelinating neurological disorders, and other variants have been associated with inherited lymphedema.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005243 gap junction channel activity
IBA
GO_REF:0000033 		ACCEPT
Summary: The ancestral channel activity is retained in human Cx47.
Reason: The actual AN0/PTN008334405 channel IBD is ancestral to human AN478. Conserved membrane architecture and target function support retention; target self-inclusion is valid experimental grounding, not circularity.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN008334405 SUPPORTS TRANSFER
Actual AN0 IBD for GO:0005243, literal donor set and target descent verified; human Q5T442 is an experimentally grounded descendant.
GO:0005243 gap junction channel activity
IEA
GO_REF:0000107 		ACCEPT
Summary: Mouse experimental channel activity supports the ortholog transfer.
Reason: The literal mouse donor has experimental channel evidence and verified one-to-one orthology. Its historical initiation boundary remains distinct from the current protein record (manual evidence, Mouse donor section).
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB:Q8BQU6 SUPPORTS TRANSFER
Actual IDA GO:0005243 donor record cites direct mouse Cx47 experiments; the corresponding Ensembl protein and one-to-one gene orthology were verified.
Supporting Evidence:
PMID:11160382
induced intercellular channels that displayed strong sensitivity to transjunctional voltage
GO:0005886 plasma membrane
IDA
GO_REF:0000052 		ACCEPT
Summary: Human Protein Atlas observations support the plasma-membrane annotation.
Reason: HPA069619 reports membrane staining in EFO-21 and SH-SY5Y, with cytosolic-only U2OS. Overall supported reliability and antibody-level uncertainty are retained. This does not establish native human glial localization.
GO:0005886 plasma membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: The UniProt membrane mapping is consistent with Cx47 channel localization.
Reason: SL-0039 is supported by the human membrane field and plaques.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER
Actual human UniProt membrane field read and supported by independent target experiments.
GO:0005921 gap junction
IEA
GO_REF:0000120 		ACCEPT
Summary: The combined donor and subcellular-location mapping supports gap junction residence.
Reason: The exact mouse protein and SL-0124 inputs are preserved. Experimental donor junctional localization, verified orthology and the human location field support transfer; unrelated human-return inference rows do not make this source circular.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB:Q8BQU6 SUPPORTS TRANSFER
Actual IDA gap-junction record and selected mouse channel/plaque experiments verified.
UniProtKB-SubCell:SL-0124 SUPPORTS TRANSFER
Actual human UniProt gap-junction field corroborates the retained location mapping.
GO:0005921 gap junction
IMP
PMID:17344063
Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-... 		ACCEPT
Summary: Wild-type human Cx47 forms junctional plaques in the cited study.
Reason: Wild-type plaques support this location; rhesus tissue and mutant ER retention remain separate.
GO:0005922 connexin complex
IBA
GO_REF:0000033 		ACCEPT
Summary: Connexon membership is retained from the verified ancestral node.
Reason: The actual AN0/PTN008334405 complex IBD is ancestral to the target. Retained topology and channel function support inheritance, without claiming a newly measured human hexamer structure or specific heteromeric composition.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN008334405 SUPPORTS TRANSFER
Actual AN0 GO:0005922 IBD, donor set and target descent verified against the retained tree and alignment.
GO:0005922 connexin complex
IEA
GO_REF:0000002 		ACCEPT
Summary: The connexin family mapping supports membership in the channel-forming complex.
Reason: Both literal connexin features occur on Q5T442 and support its channel-subunit role. Opposing-cell channel pairing does not establish mixed subunits within a single connexon.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR000500 SUPPORTS TRANSFER
Actual human connexin family feature supports the complex-subunit role.
InterPro:IPR017990 SUPPORTS TRANSFER
Actual conserved connexin site is consistent with the retained channel-forming complex.
GO:0007154 cell communication
IEA
GO_REF:0000002 		TOO GENERAL
Summary: The family mapping is biologically compatible but less informative than existing communication terms.
Reason: Actual IPR000500/IPR017990 features support the family mapping. GO:0007267 and GO:0010644 are direct is_a children of GO:0007154 and already retained. The broad term adds no specific coverage; no duplicate replacement is needed.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
Sources checked:
InterPro:IPR000500 SUPPORTS TRANSFER
Actual connexin family feature supports the broad biology; retained child terms are more informative.
InterPro:IPR017990 SUPPORTS TRANSFER
Actual connexin conserved-site feature is compatible; no family or source error is asserted.
GO:0007267 cell-cell signaling
IBA
GO_REF:0000033 		ACCEPT
Summary: Ancestral gap junction-mediated signaling is retained.
Reason: The actual AN0/PTN008334405 signaling IBD lies on the target lineage. Gap-junction communication fits this term beyond the separately retained electrical facet; no receptor or ligand mechanism is inferred.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN008334405 SUPPORTS TRANSFER
Actual AN0 GO:0007267 IBD, exact grouped donors and target path verified; channel-mediated communication fits the retained clade.
GO:0010644 cell communication by electrical coupling
IMP
PMID:17344063
Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-... 		ACCEPT
Summary: Current transfer between adjacent cells is directly supported.
Reason: Paired-cell currents directly establish electrical communication; construct limits remain.
GO:0043209 myelin sheath
IEA
GO_REF:0000107 		ACCEPT
Summary: Mouse myelin localization supports an orthology-based human annotation.
Reason: Knockout-controlled mouse IHC supports the donor annotation. Retain the orthology inference, while restricting human core locations to plasma membrane and gap junction; direct human sheath localization remains unresolved.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB:Q8BQU6 SUPPORTS TRANSFER
Mouse myelin-sheath IDA and knockout-controlled IHC support the ortholog transfer to the central glial channel context.
Supporting Evidence:
PMID:20578039
connexin47 (Cx47) in oligodendrocytes and myelin of mice
GO:0055085 transmembrane transport
IEA
GO_REF:0000108 		ACCEPT
Summary: Solute conduction through the membrane pore is a direct transport role.
Reason: GO:0005243 describes connexons passing through each adjacent membrane. The channel supplies the transport pore; GO:0055085 does not require an unapposed membrane. No unapposed-hemichannel activity is inferred.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
GO:0005243 SUPPORTS TRANSFER
Verified channel definition and target function support direct transmembrane solute conduction through connexons.
GO:1903763 gap junction channel activity involved in cell communication by electrical coupling
IMP
PMID:17344063
Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-... 		ACCEPT
Summary: Human Cx47 directly supports electrical coupling through gap junction channels.
Reason: Human currents support the existing precomposed term. The core separately represents its channel activity and electrical-coupling process; no extra function is inferred.

Core Functions

Connexin-47 supplies a gap-junction pore for electrical coupling and intercellular solute transfer.

Molecular Function:
gap junction channel activity
Directly Involved In:
cell communication by electrical coupling transmembrane transport
Cellular Locations:
plasma membrane gap junction
In Complex:
connexin complex
Supporting Evidence:
  • PMID:17344063
    robust transfer in cells expressing wild type Cx47
  • PMID:19056803
  • file:human/GJC2/GJC2-deep-research-manual.md
    Opposing-cell pairing is not heteromeric coassembly.

References

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Suggested Questions for Experts

Q: Which translation start predominates in endogenous human Cx47, and do the three N-terminal residues absent from historical constructs affect channel behavior?

Q: How closely does endogenous human myelin localization match the experimentally established mouse pattern?

Q: Which native connexon subunit combinations underlie Cx47 coupling, distinguished from heterotypic channels formed by connexons in opposing cells?

Q: How do lymphedema-associated variants affect channel function in lymphatic cells?

Suggested Experiments

Experiment: Compare sequence-verified 439- and 436-residue human constructs at matched expression, testing surface localization, dye transfer and paired-cell currents; independently resolve endogenous initiation.

Type: Controlled construct comparison and endogenous N-terminal identification

Deep Research

Manual

(GJC2-deep-research-manual.md)

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📚 Additional Documentation

Notes

(GJC2-notes.md)

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Source Guide

(GJC2-source-guide.md)

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📄 View Raw YAML

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