GJA4

Summary

GJA4 (gap junction protein alpha 4, HGNC:4278) is a protein-coding gene on chromosome 1p34.3, encoding Gap junction alpha-4 protein (P35212). One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

This gene encodes 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. Mutations in this gene have been associated with atherosclerosis and a higher risk of myocardial infarction.

Source: NCBI Gene 2701 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 59 total — 1 pathogenic
• MANE Select transcript: NM_002060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4278
Approved symbol	GJA4
Name	gap junction protein alpha 4
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	CX37
Ensembl gene	ENSG00000187513
Ensembl biotype	protein_coding
OMIM	121012
Entrez	2701

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000342280, ENST00000450137, ENST00000868038, ENST00000868039, ENST00000868040, ENST00000971021, ENST00000971022

RefSeq mRNA: 1 — MANE Select: NM_002060 NM_002060

CCDS: CCDS30669

Canonical transcript exons

ENST00000342280 — 2 exons

Exon	Start	End
ENSE00001389199	34794197	34795747
ENSE00001796424	34792999	34793068

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 96.66.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3164 / max 248.7448, expressed in 413 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2082	3.3164	413

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial artery	UBERON:0007610	96.66	gold quality
popliteal artery	UBERON:0002250	96.64	gold quality
apex of heart	UBERON:0002098	96.05	gold quality
omental fat pad	UBERON:0010414	94.94	gold quality
peritoneum	UBERON:0002358	94.91	gold quality
right lung	UBERON:0002167	94.41	gold quality
aorta	UBERON:0000947	93.85	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.79	gold quality
vena cava	UBERON:0004087	93.50	gold quality
heart left ventricle	UBERON:0002084	93.33	gold quality
cardiac ventricle	UBERON:0002082	93.23	gold quality
left coronary artery	UBERON:0001626	93.14	gold quality
coronary artery	UBERON:0001621	92.82	gold quality
right lobe of thyroid gland	UBERON:0001119	92.81	gold quality
right coronary artery	UBERON:0001625	92.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.33	gold quality
heart right ventricle	UBERON:0002080	91.35	gold quality
heart	UBERON:0000948	91.30	gold quality
left uterine tube	UBERON:0001303	91.25	gold quality
right atrium auricular region	UBERON:0006631	90.79	gold quality
tibial nerve	UBERON:0001323	90.73	gold quality
left lobe of thyroid gland	UBERON:0001120	90.53	gold quality
ascending aorta	UBERON:0001496	90.43	gold quality
thoracic aorta	UBERON:0001515	90.35	gold quality
adipose tissue	UBERON:0001013	89.87	gold quality
cardiac atrium	UBERON:0002081	89.76	gold quality
right uterine tube	UBERON:0001302	89.63	gold quality
gastrocnemius	UBERON:0001388	89.15	gold quality
thyroid gland	UBERON:0002046	89.15	gold quality
upper lobe of left lung	UBERON:0008952	89.12	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	1288.29
E-MTAB-8271	yes	799.14
E-GEOD-135922	yes	50.48
E-MTAB-8142	yes	41.14
E-CURD-112	yes	34.48
E-HCAD-11	yes	23.95
E-MTAB-8410	yes	16.71
E-MTAB-9067	yes	11.84
E-GEOD-134144	yes	11.64
E-GEOD-137537	yes	6.20
E-MTAB-10137	yes	3.87
E-MTAB-6678	no	2.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APLNR, CTNNB1, FOXO3, KLF2

miRNA regulators (miRDB)

20 targeting GJA4, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-1266-3P	96.23	66.36	778
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-1539	92.91	60.97	91

Literature-anchored findings (GeneRIF, showing 40)

• mRNA levels of connexins in different sizes of luteinized normal and hyperstimulated follicles. (PMID:14667880)
• These data suggest that alterations of specific connexins, in this case connexin 37, and resulting changes in intercellular communication may modulate endothelial cell growth and death. (PMID:15194487)
• NO inhibits the intercellular transfer of small molecules by a specific influence on Cx37 (PMID:15481066)
• Here, data for human connexin37 (hCx37) hemichannels indicate that voltage gating can be explained as block/unblock without the necessity for an independent voltage gate. (PMID:15504903)
• T1019 Cx37 SNP has shown to be a risk factor for acute myocardial infarction (AMI). (PMID:15982495)
• This is the first study to demonstrate that flow simultaneously and differentially regulates expression of the Cx37, Cx40, and Cx43 proteins. (PMID:16361362)
• investigated whether the allelic variants 1019C and 1019T are differentially predictive of increased risk for coronary artery disease (CAD) and myocardial infarction (MI) (PMID:16677656)
• The connexin37 C1019T polymorphism is not related with markers of subclinical atherosclerosis in young adults in Finland (PMID:17196598)
• Cx37 is expressed in the vascular endothelium as well as in monocytes and macrophages and these three cell types are key players in atherogenesis. (PMID:17318613)
• Connexin 37 is expressed in the granulosa layer of follicles in the human ovary, and expression of Cx37 in granulosa cells was not different between poor responder and nonpoor responder to ovulation induction. (PMID:17531234)
• This study investigates the responses of endothelial connexin 37, connexin 40, and connexin 43 (Cx37, Cx40, and Cx43) to shear stress and substrate. (PMID:17922338)
• Study suggests that GJA4 gene C1019T polymorphism and/or its related C-C-D haplotype might contribute to an increased risk of CAD and potentially play an important role in the development of coronary atherosclerosis in northern Han Chinese. (PMID:18073482)
• variation in the connexin gene may modify effects risk factors have on vascular function (PMID:18605953)
• As much as half the length of the connexin N-terminus can be deleted without affecting formation of gap junction plaques, but an intact N-terminus is required for hemichannel gating and intercellular communication. (PMID:18664489)
• The electrical properties of Cx37 hemichannels (HCs) and gap junction channels (GJCs) were measured with voltage-clamp methods. (PMID:19166859)
• connexin37 C1019T polymorphism is associated with peripheral artery disease in Japanese type 2 diabetic patients. (PMID:19407064)
• The alpha helical structure of the connexin 37 N terminus may be dispensable for protein localization, but it is required for channel and hemichannel function. (PMID:19478091)
• Data show for the first time a functional and specific interaction between eNOS and Cx37 in endothelial cells. (PMID:20081116)
• Results show that Cx40, Cx37, Cx43 and Cx45 were expressed within the glomeruli. (PMID:20530971)
• Cx37 C1019T polymorphism is associated with tumour cell proliferation. (PMID:20705954)
• Connexin 37 genetic variants significantly affect carotid IMT and contribute to future development of ischemic stroke (PMID:21044781)
• Endothelium-dependent vasodilation is primarily mediated by connexin 37 in mesenteric artery. (PMID:21172909)
• The gene for Cx37 was associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with advanced central obesity. (PMID:21208019)
• In women with higher fasting glycemia TT genotype of Cx37 polymorphism was protective against subclinical atherosclerosis. (PMID:21617605)
• We propose that the establishment of gap junctional communication between Cx37-expressing platelets provides a mechanism to limit thrombus propensity. (PMID:21810657)
• GJA4 polymorphism is not associated with stroke risk in the Taiwanese population. (PMID:22305353)
• We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. (PMID:22528526)
• The data show that induced expression of either Cx37 or Cx40 in Cx43-expressing cells can selectively alter the intercellular exchange of some molecules without affecting the transfer of others. (PMID:22729648)
• C1019T polymorphism in the connexin 37 gene is associated with Helicobacter pylori infection and gastric cancer. (PMID:22901223)
• It is suggested that the polymorphism in the Cx37 gene (but not Cx40 gene) potentially plays a significant role in the manifestation of AMI disease in Iranian population (PMID:23724624)
• 1019C/T polymorphism in the CX37 gene is associated with susceptibility to coronary artery disease as well as restenosis after coronary stenting in male patients. (PMID:23926016)
• Determination of Cx37 C1019T and eNOS G894T polymorphisms may be used to detect a genetic predisposition to the development of myocardial infarction in patients with hemodynamically insignificant atherosclerosis and in apparently healthy individuals. (PMID:24261225)
• the C1019T polymorphism may be a moderate risk factor for MI and that DM was likely a potential source of between-study heterogeneity. [META-ANALYSIS] (PMID:24333099)
• The C allele in the CX37 gene might be associated with the susceptibility to EH in population of Wuxi, China. (PMID:24685073)
• three variants in PNPLA3 gene may be a genetic risk factor for NASH (PMID:24773516)
• Review/Meta-analysis: Cx37 C1019T was a risk factor for myocardial infarction and a protective factor for coronary artery disease. (PMID:24937033)
• The C allele in the CX37 gene might be associated with susceptibility to dilated cardiomyopathy (DCM) in Chinese Han; female carriers of the C allele had higher DCM risk compared with TT homozygotes than males (PMID:25501978)
• The protective effect of the T allele of the Cx37 gene might be strongly modified by smoking; in women, this effect could be mediated through stem cells. (PMID:26588185)
• Our findings suggest that the Cx37 C1019T variation may contribute to the risk of PCOS in the South Indian women. (PMID:26656196)
• The CX37 rs1764390 G allele is associated with increased susceptibility to sepsis, which may be involved in the process of sepsis via mediating the plasma levels of NO, IL-6 and CRP. (PMID:27939333)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gja4	ENSDARG00000070357
mus_musculus	Gja4	ENSMUSG00000050234
rattus_norvegicus	Gja4	ENSRNOG00000014357

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), GJC1 (ENSG00000182963), GJD3 (ENSG00000183153), GJB3 (ENSG00000188910), GJB5 (ENSG00000189280), GJB4 (ENSG00000189433), GJC2 (ENSG00000198835), GJE1 (ENSG00000203733), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction alpha-4 protein — P35212 (reviewed: P35212)

Alternative names: Connexin-37

All UniProt accessions (2): P35212, Q5JW71

UniProt curated annotations — full annotation on UniProt →

Function. One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

Subunit / interactions. A connexon is composed of a hexamer of connexins.

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

Tissue specificity. Expressed in multiple organs and tissues, including heart, uterus, ovary, and blood vessel endothelium.

Similarity. Belongs to the connexin family. Alpha-type (group II) subfamily.

RefSeq proteins (1): NP_002051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000500	Connexin	Family
IPR002263	Connexin37	Family
IPR013092	Connexin_N	Domain
IPR017990	Connexin_CS	Conserved_site
IPR019570	Connexin_CCC	Domain
IPR038359	Connexin_N_sf	Homologous_superfamily

Pfam: PF00029

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35212-F1	74.82	0.33

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-190861	Gap junction assembly

MSigDB gene sets: 139 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, WWTAAGGC_UNKNOWN, GCANCTGNY_MYOD_Q6, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, BROWNE_HCMV_INFECTION_14HR_DN, chr1p34, BROWNE_HCMV_INFECTION_24HR_DN, GOBP_CELL_JUNCTION_ASSEMBLY, REACTOME_GAP_JUNCTION_ASSEMBLY, WESTON_VEGFA_TARGETS_6HR, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION

GO Biological Process (5): blood vessel development (GO:0001568), cell-cell junction assembly (GO:0007043), cell-cell signaling (GO:0007267), cell communication (GO:0007154), transmembrane transport (GO:0055085)

GO Molecular Function (2): gap junction channel activity (GO:0005243), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), gap junction (GO:0005921), connexin complex (GO:0005922), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Gap junction trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
vasculature development	1
anatomical structure development	1
cell junction assembly	1
cell-cell junction organization	1
cell communication	1
signaling	1
transport	1
wide pore channel activity	1
binding	1
membrane	1
cell periphery	1
cell-cell junction	1
gap junction	1
plasma membrane protein complex	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1273 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GJA4	GJA5	P36382	955
GJA4	GJA1	P17302	900
GJA4	GJC1	P36383	836
GJA4	PANX1	Q96RD7	570
GJA4	SERPINE1	P05121	557
GJA4	RIC1	Q4ADV7	549
GJA4	GDF9	O60383	538
GJA4	BMP15	O95972	522
GJA4	FOXC2	Q99958	514
GJA4	MMP3	P08254	492
GJA4	PKP2	Q99959	484
GJA4	EFNB2	P52799	481
GJA4	PANX2	Q96RD6	478
GJA4	HIGD1B	Q9P298	471
GJA4	PANX3	Q96QZ0	470

IntAct

18 interactions, top by confidence:

A	B	Type	Score
GJA4	OPRM1	psi-mi:“MI:0915”(physical association)	0.630
OPRM1	GJA4	psi-mi:“MI:0915”(physical association)	0.630
TMEM86B	GJA4	psi-mi:“MI:0915”(physical association)	0.560
GJA4		psi-mi:“MI:0915”(physical association)	0.560
GJA4	CD81	psi-mi:“MI:0915”(physical association)	0.560
GJA4	MS4A13	psi-mi:“MI:0915”(physical association)	0.560
GJA4	TMEM86B	psi-mi:“MI:0915”(physical association)	0.560
GJA4	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
GJA4	Oprd1	psi-mi:“MI:0915”(physical association)	0.400
	GJA4	psi-mi:“MI:0915”(physical association)	0.000
CD81	GJA4	psi-mi:“MI:0915”(physical association)	0.000
MS4A13	GJA4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): GJA4 (Two-hybrid), GJA4 (Affinity Capture-Western), GJA4 (Affinity Capture-Western), GJA4 (Affinity Capture-Western), GJA4 (Two-hybrid), GJA4 (Two-hybrid), GJA4 (Two-hybrid), MS4A13 (Two-hybrid), GJA4 (Two-hybrid), MAP1LC3B (Affinity Capture-Western), GJA4 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIJ0, A1L3G9, A4IFL1, B9X187, O18968, O70491, P08033, P08034, P28230, P35212, P36380, P51915, P60572, Q02738, Q059Y8, Q0V8E7, Q1LXZ7, Q28FG4, Q29559, Q4QR83, Q5E9Z5, Q5FVF4, Q5FWS4, Q5JW98, Q5R7B4, Q5T197, Q5T1A1, Q60HF7, Q640M6, Q6GMB1, Q6WGK6, Q7SY10, Q7TNJ0, Q8BXV2, Q8C2L6, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NDZ6

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
996750	NM_002060.3(GJA4):c.121G>T (p.Gly41Cys)	Pathogenic

SpliceAI

245 predictions. Top by Δscore:

Variant	Effect	Δscore
1:34794191:TTGCA:T	acceptor_loss	1.0000
1:34794192:TGCAG:T	acceptor_loss	1.0000
1:34794193:GCA:G	acceptor_loss	1.0000
1:34794194:CAGAC:C	acceptor_loss	1.0000
1:34794195:A:AG	acceptor_gain	1.0000
1:34794195:AGAC:A	acceptor_gain	1.0000
1:34794195:AGACG:A	acceptor_gain	1.0000
1:34794196:G:GA	acceptor_gain	1.0000
1:34794196:GAC:G	acceptor_gain	1.0000
1:34794196:GACG:G	acceptor_gain	1.0000
1:34794196:GACGG:G	acceptor_gain	1.0000
1:34793065:GGCG:G	donor_gain	0.9900
1:34793066:GCGG:G	donor_gain	0.9900
1:34793069:G:GG	donor_gain	0.9900
1:34793063:C:T	donor_gain	0.9800
1:34793066:GCG:G	donor_gain	0.9800
1:34793066:GCGGT:G	donor_loss	0.9800
1:34793067:CGG:C	donor_loss	0.9800
1:34793069:G:C	donor_loss	0.9800
1:34793070:T:G	donor_loss	0.9800
1:34793071:GA:G	donor_loss	0.9800
1:34794192:T:TA	acceptor_gain	0.9800
1:34794196:GA:G	acceptor_gain	0.9800
1:34793072:AGT:A	donor_loss	0.9700
1:34793064:AGGCG:A	donor_gain	0.9300
1:34793065:GGCGG:G	donor_gain	0.9300
1:34793067:CG:C	donor_gain	0.8900
1:34793068:GG:G	donor_gain	0.8900
1:34793073:G:C	donor_loss	0.8600
1:34794198:CGG:C	acceptor_gain	0.8200

AlphaMissense

2131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:34794348:G:C	W45C	1.000
1:34794348:G:T	W45C	1.000
1:34794373:T:A	C54S	1.000
1:34794374:G:C	C54S	1.000
1:34794286:T:A	W25R	0.999
1:34794286:T:C	W25R	0.999
1:34794346:T:A	W45R	0.999
1:34794346:T:C	W45R	0.999
1:34794368:T:G	F52C	0.999
1:34794373:T:C	C54R	0.999
1:34794375:T:G	C54W	0.999
1:34794394:T:A	C61S	0.999
1:34794395:G:C	C61S	0.999
1:34794406:T:A	C65S	0.999
1:34794407:G:A	C65Y	0.999
1:34794407:G:C	C65S	0.999
1:34794408:C:G	C65W	0.999
1:34794421:T:C	F70L	0.999
1:34794423:C:A	F70L	0.999
1:34794423:C:G	F70L	0.999
1:34794469:A:C	S86R	0.999
1:34794471:C:A	S86R	0.999
1:34794471:C:G	S86R	0.999
1:34794476:C:A	P88H	0.999
1:34794476:C:G	P88R	0.999
1:34794718:T:C	F169L	0.999
1:34794720:C:A	F169L	0.999
1:34794720:C:G	F169L	0.999
1:34794805:T:A	C198S	0.999
1:34794806:G:C	C198S	0.999

dbSNP variants (sampled 300 via entrez): RS1000583073 (1:34795506 T>C), RS1001594198 (1:34791735 A>G), RS1003375913 (1:34793347 G>A), RS1003404658 (1:34792874 G>A), RS1004597042 (1:34793209 G>A), RS1006556859 (1:34795533 C>A,G,T), RS1006608620 (1:34795830 C>A,T), RS1007926919 (1:34792476 T>A,G), RS1008045483 (1:34795867 C>T), RS1009346133 (1:34793780 G>A), RS1011021167 (1:34792422 T>C), RS1011371178 (1:34792176 T>C,G), RS1011873019 (1:34792977 G>C,T), RS1012447395 (1:34795049 C>G,T), RS1012516672 (1:34791584 AG>A)

Disease associations

OMIM: gene MIM:121012 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): liver hemangioma (MONDO:0002404), skin hemangioma (MONDO:0003110)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001549_5	Formal thought disorder in schizophrenia	9.000000e-06
GCST009612_3	Triglyceride levels x thiazide or thiazide-like diuretics use interaction	6.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004805	formal thought disorder
EFO:0004530	triglyceride measurement

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects expression	4
Progesterone	affects cotreatment, decreases expression, increases expression	3
Estradiol	affects cotreatment, decreases expression	2
bisphenol F	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
terbufos	increases methylation	1
arsenite	increases methylation	1
methylparaben	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
epigallocatechin gallate	decreases expression	1
astragaloside A	decreases expression, decreases reaction	1
entinostat	decreases expression	1
malondialdehyde-low density lipoprotein, human	decreases expression, decreases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Lycopene	decreases expression	1
Vorinostat	decreases expression	1
Acetylcysteine	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Oxygen	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01785212	Not specified	COMPLETED	The Influence of Two Different Hepatectomy Methods on Transection Speed and Chemokine Release From the Liver
NCT04709718	Not specified	COMPLETED	Surgical Management of Giant Hepatic Hemangioma