GJC1

Summary

GJC1 (gap junction protein gamma 1, HGNC:4280) is a protein-coding gene on chromosome 17q21.31, encoding Gap junction gamma-1 protein (P36383). Structural component of the gap junction, a specialized intercellular structure consisting of a cluster of closely packed pairs of transmembrane channels, the connexons, that allow passage of small molecules and electrical signals between neighboring cells.

This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Alternatively spliced transcript variants encoding the same isoform have been described.

Source: NCBI Gene 10052 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_005497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4280
Approved symbol	GJC1
Name	gap junction protein gamma 1
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	CX45
Ensembl gene	ENSG00000182963
Ensembl biotype	protein_coding
OMIM	608655
Entrez	10052

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000330514, ENST00000586267, ENST00000586347, ENST00000587113, ENST00000587239, ENST00000590758, ENST00000591424, ENST00000592524, ENST00000907279, ENST00000907280, ENST00000907281, ENST00000907282, ENST00000907284, ENST00000920109, ENST00000920110, ENST00000920111, ENST00000920112, ENST00000920113, ENST00000964185, ENST00000964186

RefSeq mRNA: 2 — MANE Select: NM_005497 NM_001080383, NM_005497

CCDS: CCDS11487

Canonical transcript exons

ENST00000592524 — 3 exons

Exon	Start	End
ENSE00001311342	44798448	44805837
ENSE00001515699	44807394	44807469
ENSE00001515700	44830062	44830287

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 94.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5710 / max 74.8246, expressed in 1130 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166400	3.5710	1130
166401	1.4925	542

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	94.91	gold quality
seminal vesicle	UBERON:0000998	93.81	gold quality
cartilage tissue	UBERON:0002418	91.69	gold quality
secondary oocyte	CL:0000655	91.19	gold quality
adult organism	UBERON:0007023	90.90	gold quality
visceral pleura	UBERON:0002401	90.25	gold quality
saphenous vein	UBERON:0007318	89.84	gold quality
placenta	UBERON:0001987	88.76	gold quality
ventricular zone	UBERON:0003053	88.53	gold quality
colonic epithelium	UBERON:0000397	88.50	gold quality
myometrium	UBERON:0001296	87.89	gold quality
cortical plate	UBERON:0005343	87.76	gold quality
urethra	UBERON:0000057	87.60	gold quality
ganglionic eminence	UBERON:0004023	87.51	gold quality
parietal pleura	UBERON:0002400	87.50	gold quality
oocyte	CL:0000023	87.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.89	gold quality
pleura	UBERON:0000977	86.81	gold quality
body of uterus	UBERON:0009853	86.18	gold quality
stromal cell of endometrium	CL:0002255	86.11	gold quality
smooth muscle tissue	UBERON:0001135	86.07	gold quality
decidua	UBERON:0002450	85.97	gold quality
lower lobe of lung	UBERON:0008949	85.84	gold quality
sural nerve	UBERON:0015488	84.88	gold quality
heart right ventricle	UBERON:0002080	84.23	gold quality
tendon of biceps brachii	UBERON:0008188	83.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.86	gold quality
apex of heart	UBERON:0002098	82.42	gold quality
uterus	UBERON:0000995	81.80	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	39.46
E-ANND-3	yes	13.63
E-MTAB-6678	yes	11.48
E-GEOD-111727	no	173.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

180 targeting GJC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 25)

• Data suggest that the dynamic changes of connexins 43, 40 and 45 during mouse cardiac development appear to be mirrored in the human. (PMID:12064615)
• abnormal expression of connexin43 and connexin45 in nasopharynx tissues may be associated with cancerization and squamatization of human nasopharynx tissue (PMID:12452056)
• mRNA levels of connexins in different sizes of luteinized normal and hyperstimulated follicles. (PMID:14667880)
• The staining patterns for Cx45 rather were typified by granular cytoplasmic staining. (PMID:14766937)
• Cx45 has a complex binding interaction with zonula occludens-1 (ZO-1) that involves either an extended carboxyl terminal domain or two distinct binding sites. (PMID:16463142)
• Cx40/Cx45 junctions demonstrate electrical signal transfer asymmetry that can be modulated between unidirectional and bidirectional by small changes in the difference between holding potentials of the coupled cells. (PMID:17189315)
• a cross-talk between CFTR and a variety of gap junction channels. Cytoskeletal scaffolding proteins and/or other intermediate cytoplasmic proteins are likely to play a role in CFTR-connexins interaction. (PMID:17546509)
• Studies indicate that 21 different Cxs have been detected and they are generally named according to their approximate molecular mass in Kda, e.g. Cx32, Cx43 and Cx45. (PMID:19883623)
• Results show that Cx40, Cx37, Cx43 and Cx45 were expressed within the glomeruli. (PMID:20530971)
• connexin genes Gjd2 coding for mCx36, Gjc1 coding for mCx45 and Gja10 coding for mCx57 in the mouse, a subset of 4 connexin genes, including the unique GJA9 (Cx59) and GJA10 (Cx62), could be detected at least as transcript isoforms in the human retina. (PMID:20979653)
• Our data suggest that GJA7 alterations have no or low genetic relevance in nonsyndromic hearing loss in populatins from Turkey, South Africa, United Kingdom, United States, and China. (PMID:21254920)
• DNA hypermethylation of the promoter region of GJC1, encoding connexin45, is an important mechanism in silencing gene expression in colorectal cancer. (PMID:21406965)
• Study shows that fusion of a V5/6-His tag (hexa moiety M r = 0.93 kDa) to the CT segment of Cx40, Cx43 and Cx45 does not prevent the cells from forming channels. (PMID:21424225)
• Gap junctional intercellular communication in human bladder smooth muscle cells and suburothelial myofibroblastsdepend of Cx43 rather than on Cx45. (PMID:21674053)
• Results found that the expression of Cx26 and Cx45 had no prognostic value but Cx43 was upregulated in tumour epithelia and membrane Cx43 expression was associated with short overall survival time. (PMID:24788723)
• Connexin45 has much more rapid gating kinetics than connexin43 (PMID:25401181)
• Human deltoid muscle biopsies of 5 Chilean dysferlinopathy patients exhibited the presence of muscular connexins (Cx40.1, Cx43 and Cx45). (PMID:27229680)
• our data highlighted the critical role of CX45 in reprogramming and may increase the cell division rate and result in an accelerated kinetics of iPSCs production. (PMID:28352086)
• human Cx40/Cx45 and Cx43/Cx45 heterotypic gap junctions were investigated by recombinant expression in GJ deficient cells. (PMID:28760564)
• Observations involving both N- and C-domains of CaM to interact with the Cx45 peptide differ from the embraced interaction with Cx50 from another connexin family (PMID:28963343)
• The HG-stimulated proliferative capacity was abolished upon decreasing O-GlcNAcylation, which could be reversed gradually by the simultaneous overexpression of APA1 and GJC1. Therefore, GJC1 could be a potential target for preventing liver cancer in patients with diabetes. (PMID:30078215)
• Cx40 or Cx45 Gap junctions showed little changes in the extent of voltage-dependent-gating, but in both cases with a faster deactivation kinetics at high temperatures. (PMID:30594539)
• Identification of Cx45 as a Major Component of GJs in HeLa Cells. (PMID:33003547)
• Connexin45 (GJC1) loss-of-function mutation contributes to familial atrial fibrillation and conduction disease. (PMID:33429106)
• The role of the Cx43/Cx45 gap junction voltage gating on wave propagation and arrhythmogenic activity in cardiac tissue. (PMID:37684404)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gjc1	ENSMUSG00000034520
rattus_norvegicus	Gjc1	ENSRNOG00000048838

Paralogs (20): GJA8 (ENSG00000121634), GJB6 (ENSG00000121742), GJA3 (ENSG00000121743), GJA9 (ENSG00000131233), GJA10 (ENSG00000135355), GJA1 (ENSG00000152661), GJD2 (ENSG00000159248), GJB7 (ENSG00000164411), GJB2 (ENSG00000165474), GJB1 (ENSG00000169562), GJC3 (ENSG00000176402), GJD4 (ENSG00000177291), GJD3 (ENSG00000183153), GJA4 (ENSG00000187513), GJB3 (ENSG00000188910), GJB5 (ENSG00000189280), GJB4 (ENSG00000189433), GJC2 (ENSG00000198835), GJE1 (ENSG00000203733), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction gamma-1 protein — P36383 (reviewed: P36383)

Alternative names: Connexin-45, Gap junction alpha-7 protein

All UniProt accessions (7): P36383, A0A654IDC0, K7EM78, K7ENT9, K7EQ14, K7ERH3, Q5H9P2

UniProt curated annotations — full annotation on UniProt →

Function. Structural component of the gap junction, a specialized intercellular structure consisting of a cluster of closely packed pairs of transmembrane channels, the connexons, that allow passage of small molecules and electrical signals between neighboring cells. Forms homotypic and heterotypic channels gated by transjunctional voltage. Involved in intercellular innate immune signaling. Mediates translocation of 2’,3’-cGAMP and 2’,5’-oligoadenylates (2-5A) second messengers from virus-infected cells to macrophages and uninfected neighboring cells to propagate and amplify the antiviral immune response.

Subunit / interactions. A connexon/hemichannel is composed of a hexamer of connexins. Forms functional homotypic gap junctions consisting of identical hemichannels both made of the same connexin type as well as heterotypic gap junctions consisting of two different hemichannels, each containing a different type of connexin. Assembles with GJA1 to form heterotypic gap junction channels. Interacts with CNST.

Subcellular location. Cell membrane. Cell junction. Gap junction.

Similarity. Belongs to the connexin family. Gamma-type subfamily.

RefSeq proteins (2): NP_001073852, NP_005488* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000500	Connexin	Family
IPR002265	Connexin45	Family
IPR013092	Connexin_N	Domain
IPR017990	Connexin_CS	Conserved_site
IPR019570	Connexin_CCC	Domain
IPR038359	Connexin_N_sf	Homologous_superfamily

Pfam: PF00029

Catalyzed reactions (Rhea), 2 shown:

• 2’,3’-cGAMP(out) = 2’,3’-cGAMP(in) (RHEA:66320)
• 5’-triphosphoadenylyl-(2’->5’)-adenylyl-(2’->5’)-adenosine(out) = 5’-triphosphoadenylyl-(2’->5’)-adenylyl-(2’->5’)-adenosine(in) (RHEA:85019)

UniProt features (16 total): topological domain 5, transmembrane region 4, region of interest 2, compositionally biased region 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3SHW	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36383-F1	69.52	0.28

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-112303	Electric Transmission Across Gap Junctions
R-HSA-190861	Gap junction assembly

MSigDB gene sets: 229 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELL_CELL_SIGNALING, BROWNE_HCMV_INFECTION_48HR_DN, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, IRF7_01, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_MUSCLE_CONTRACTION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_CELL_COMMUNICATION_INVOLVED_IN_CARDIAC_CONDUCTION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_CELL_COMMUNICATION_BY_ELECTRICAL_COUPLING, GOBP_CELL_CELL_SIGNALING_INVOLVED_IN_CARDIAC_CONDUCTION

GO Biological Process (16): vasculogenesis (GO:0001570), muscle contraction (GO:0006936), cell-cell junction assembly (GO:0007043), cell-cell signaling (GO:0007267), chemical synaptic transmission (GO:0007268), visual perception (GO:0007601), gap junction assembly (GO:0016264), cell development (GO:0048468), cardiac muscle tissue development (GO:0048738), atrial cardiac muscle cell action potential (GO:0086014), SA node cell to atrial cardiac muscle cell communication by electrical coupling (GO:0086021), AV node cell to bundle of His cell communication by electrical coupling (GO:0086053), cell communication (GO:0007154), heart development (GO:0007507), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (5): monoatomic ion channel activity (GO:0005216), gap junction channel activity (GO:0005243), gap junction channel activity involved in SA node cell-atrial cardiac muscle cell electrical coupling (GO:0086020), gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling (GO:0086077), protein binding (GO:0005515)

GO Cellular Component (10): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), gap junction (GO:0005921), connexin complex (GO:0005922), intercalated disc (GO:0014704), synapse (GO:0045202), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transmission across Electrical Synapses	1
Gap junction trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	2
cell communication by electrical coupling involved in cardiac conduction	2
cellular process	2
gap junction channel activity involved in cardiac conduction electrical coupling	2
cellular anatomical structure	2
cell junction	2
blood vessel morphogenesis	1
muscle system process	1
cell junction assembly	1
cell-cell junction organization	1
cell communication	1
signaling	1
anterograde trans-synaptic signaling	1
sensory perception of light stimulus	1
cell-cell junction assembly	1
anatomical structure development	1
cellular developmental process	1
heart development	1
striated muscle tissue development	1
cardiac muscle cell action potential involved in contraction	1
atrial cardiac muscle cell to AV node cell signaling	1
SA node cell to atrial cardiac muscle cell communication	1
AV node cell to bundle of His cell communication	1
animal organ development	1
circulatory system development	1
monoatomic ion transport	1
transmembrane transport	1
transport	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
wide pore channel activity	1
SA node cell to atrial cardiac muscle cell communication by electrical coupling	1
AV node cell to bundle of His cell communication by electrical coupling	1
binding	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GJC1	GJA1	P17302	984
GJC1	GJA5	P36382	983
GJC1	GJB6	O95452	895
GJC1	TJP1	Q07157	892
GJC1	GJE1	A6NN92	861
GJC1	GJA4	P35212	836
GJC1	HCN4	Q9Y3Q4	823
GJC1	GJD2	Q9UKL4	775
GJC1	CNST	Q6PJW8	730
GJC1	MIP	P30301	687
GJC1	TJP3	O95049	651
GJC1	GJB2	P29033	641
GJC1	NKX2-5	P52952	624
GJC1	PANX1	Q96RD7	601
GJC1	PKP2	Q99959	582

IntAct

154 interactions, top by confidence:

A	B	Type	Score
GJC1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
GJC1	SLC66A1	psi-mi:“MI:0915”(physical association)	0.560
APOL3	GJC1	psi-mi:“MI:0915”(physical association)	0.560
GJC1	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
ZACN	GPAA1	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
GJC1	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	TJP1	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	PARD3	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	TJP3	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	HTRA2	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	DVL3	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (68): GJC1 (Affinity Capture-MS), EXTL2 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Reconstituted Complex), UBQLN4 (Affinity Capture-Western), PSMD2 (Affinity Capture-Western), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1QT59, A2VEY9, A8X9H4, D3KZG3, O35412, O35607, O57474, O61366, O93383, P18861, P29415, P34535, P36383, P43322, P49414, P50605, P60571, P91682, Q02297, Q03345, Q05199, Q11069, Q13873, Q14693, Q2THW7, Q2THW9, Q2THX1, Q5R838, Q5RJX2, Q5YCC7, Q64448, Q69ZW3, Q6DR98, Q6H1V1, Q6IMP4, Q6TYA8, Q7TQ69, Q7Z5M5, Q86B91, Q8INR6

Diamond homologs: A2VE67, A4GG66, A4GVD1, A4IFL1, A6XKM2, O18968, O54851, O57474, O70610, O75712, O93533, O95377, O95452, P08033, P08034, P08050, P08983, P14154, P16863, P16864, P17302, P18246, P18860, P18861, P21994, P23242, P25305, P28228, P28229, P28230, P28231, P28232, P28233, P28234, P28235, P28236, P29033, P29414, P29415, P33725

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	7	53.3×	1e-08
Assembly and cell surface presentation of NMDA receptors	8	27.1×	5e-08
Neurexins and neuroligins	9	23.6×	2e-08
Negative regulation of MAPK pathway	5	17.7×	2e-04
Protein-protein interactions at synapses	5	17.7×	2e-04
RAF/MAP kinase cascade	8	6.5×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	46.7×	1e-10
protein localization to synapse	5	34.2×	3e-05
receptor clustering	6	33.4×	4e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	5	22.1×	2e-04
protein-containing complex assembly	9	9.2×	6e-05
cell-cell adhesion	10	9.1×	2e-05
chemical synaptic transmission	8	5.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

42 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005874 (17:44800041 G>A), RS1000037102 (17:44799699 G>T), RS1000167992 (17:44794564 C>T), RS1000176499 (17:44810933 A>G), RS1000228381 (17:44808699 T>C), RS1000330347 (17:44830230 C>A,G,T), RS1000424341 (17:44822922 T>C), RS1000564811 (17:44823172 G>A), RS1000654662 (17:44819515 G>A,C,T), RS1000845493 (17:44804982 A>G), RS1000935713 (17:44831560 G>C), RS1000945602 (17:44798310 G>A,T), RS1000957944 (17:44819293 C>T), RS1000994921 (17:44798576 T>C), RS1001233165 (17:44825719 G>A)

Disease associations

OMIM: gene MIM:608655 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other ic — Connexins and Pannexins

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression, affects expression	6
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Nickel	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Particulate Matter	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
terbufos	decreases methylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
beta-lapachone	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
dibenzo(a,l)pyrene	decreases expression	1
beta-methylcholine	affects expression	1
fumonisin B1	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
SRM 1597	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.