GJB4

Summary

GJB4 (gap junction protein beta 4, HGNC:4286) is a protein-coding gene on chromosome 1p34.3, encoding Gap junction beta-4 protein (Q9NTQ9). Structural component of gap junctions.

This gene encodes a transmembrane connexin protein that is a component of gap junctions. Mutations in this gene have been associated with erythrokeratodermia variabilis, progressive symmetric erythrokeratoderma and hearing impairment.

Source: NCBI Gene 127534 — RefSeq curated summary.

At a glance

• Gene–disease (curated): erythrokeratodermia variabilis et progressiva 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 133 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 34
• MANE Select transcript: NM_153212

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4286
Approved symbol	GJB4
Name	gap junction protein beta 4
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	CX30.3
Ensembl gene	ENSG00000189433
Ensembl biotype	protein_coding
OMIM	605425
Entrez	127534

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000339480, ENST00000919353

RefSeq mRNA: 1 — MANE Select: NM_153212 NM_153212

CCDS: CCDS383

Canonical transcript exons

ENST00000339480 — 2 exons

Exon	Start	End
ENSE00001364195	34759740	34759788
ENSE00001385373	34760933	34762327

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 92.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3722 / max 25.2716, expressed in 106 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2072	0.3722	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	92.06	gold quality
zone of skin	UBERON:0000014	91.82	gold quality
skin of leg	UBERON:0001511	91.71	gold quality
gall bladder	UBERON:0002110	74.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.16	gold quality
lower esophagus mucosa	UBERON:0035834	70.80	gold quality
esophagus mucosa	UBERON:0002469	70.00	gold quality
vagina	UBERON:0000996	60.70	gold quality
islet of Langerhans	UBERON:0000006	56.22	gold quality
tonsil	UBERON:0002372	54.23	gold quality
urinary bladder	UBERON:0001255	54.20	gold quality
prostate gland	UBERON:0002367	52.07	gold quality
esophagus	UBERON:0001043	51.39	gold quality
minor salivary gland	UBERON:0001830	50.84	gold quality
vermiform appendix	UBERON:0001154	50.39	gold quality
rectum	UBERON:0001052	50.08	gold quality
saliva-secreting gland	UBERON:0001044	49.79	gold quality
stromal cell of endometrium	CL:0002255	49.12	gold quality
placenta	UBERON:0001987	46.75	gold quality
right lobe of liver	UBERON:0001114	42.32	silver quality
fallopian tube	UBERON:0003889	42.14	gold quality
pancreas	UBERON:0001264	42.09	gold quality
skeletal muscle tissue	UBERON:0001134	41.02	gold quality
mucosa of transverse colon	UBERON:0004991	40.53	silver quality
multicellular organism	UBERON:0000468	39.59	gold quality
right lung	UBERON:0002167	39.01	gold quality
gastrocnemius	UBERON:0001388	38.25	gold quality
bone marrow cell	CL:0002092	38.08	gold quality
muscle tissue	UBERON:0002385	37.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	37.73	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting GJB4, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587

Literature-anchored findings (GeneRIF, showing 16)

• A common frameshift mutation and other variants in GJB4 (connexin 30.3): Analysis of hearing impairment families (PMID:11933201)
• the involvement of connexin gene 30.3 (GJB4) in the etiology of erythrokeratodermia variabilis (PMID:12648223)
• These results not only provide new insights into epidermal connexin synthesis and polymerization, but also allow a novel molecular explanation for the similarity of EKV phenotypes. (PMID:14583444)
• Not all clinically diagnosed individuals with erythrokeratoderma variabilis harbor Cx30.3 disease-associated mutations. (PMID:16297190)
• Five patients with erythrokeratodermia variabilis of Mendes da Costa and progressive symmetric erythrokeratodermia of Gottron had the same mutation in the GJB4 gene causing the amino acid substitution p.Gly12Asp (G12D). (PMID:19291775)
• There were no mutations found in the GJB4 gene and the true pathogenesis of progressive symmetrical erythrokeratodermia remains unknown. (PMID:21198793)
• Mutation analysis of GJB3 and GJB4 in Chinese patients with erythrokeratodermia variabilis. (PMID:21950330)
• Bidirectional sequencing of the coding region of GJB4 revealed a novel c.295G>A missense mutation. (PMID:22266302)
• Letter: describe erythrokeratodermia variabilis phenotype related to novel mutation in GJB4 gene. (PMID:23037955)
• In this study, we found no mutations of GJB4 in two Progressive symmetrical erythrokeratoderma families. (PMID:23678955)
• GJB4 may be a genetic risk factor for the development of nonsyndromic hearing loss and the data from the present study can be used to direct the clinical evaluation and effectively manage the care of families of children with GJB4. (PMID:25333454)
• study has identified Gjb4 as a potential novel diagnostic and prognostic biomarker for lung cancer. Targeting Gjb4 may be exploited as a modality for improving lung cancer therapy. (PMID:30177841)
• Clinical variability of the GJB4:c.35G > A gene variant: a study of a large Brazilian erythrokeratodermia pedigree. (PMID:32311086)
• GJB4 and GJC3 variants in non-syndromic hearing impairment in Ghana. (PMID:32524838)
• Gap junction protein beta 4 plays an important role in cardiac function in humans, rodents, and zebrafish. (PMID:33048975)
• Gap junction beta-4 accelerates cell cycle progression and metastasis through MET-AKT activation in pancreatic cancer. (PMID:38342100)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gjb10	ENSDARG00000075854
mus_musculus	Gjb4	ENSMUSG00000046623
rattus_norvegicus	Gjb4	ENSRNOG00000026910

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), GJA4 (ENSG00000187513), GJB3 (ENSG00000188910), GJB5 (ENSG00000189280), GJC2 (ENSG00000198835), GJE1 (ENSG00000203733), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction beta-4 protein — Q9NTQ9 (reviewed: Q9NTQ9)

Alternative names: Connexin-30.3

All UniProt accessions (2): A0A654IBS8, Q9NTQ9

UniProt curated annotations — full annotation on UniProt →

Function. Structural component of gap junctions. Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane. Small molecules and ions diffuse from one cell to a neighboring cell via the central pore.

Subunit / interactions. A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels. Forms heteromeric channels with GJB2.

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

Disease relevance. Erythrokeratodermia variabilis et progressiva 2 (EKVP2) [MIM:617524] A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the connexin family. Beta-type (group I) subfamily.

RefSeq proteins (1): NP_694944* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000500	Connexin	Family
IPR002270	Connexin-30.3	Family
IPR013092	Connexin_N	Domain
IPR017990	Connexin_CS	Conserved_site
IPR019570	Connexin_CCC	Domain
IPR038359	Connexin_N_sf	Homologous_superfamily

Pfam: PF00029

UniProt features (24 total): sequence variant 10, topological domain 5, transmembrane region 4, disulfide bond 3, chain 1, intramembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NTQ9-F1	78.75	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 53–175, 60–169, 64–164

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-190861	Gap junction assembly

MSigDB gene sets: 152 (showing top): RNGTGGGC_UNKNOWN, GOBP_BEHAVIOR, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, REACTOME_MEMBRANE_TRAFFICKING, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, GOBP_CELL_CELL_SIGNALING, GOBP_CHEMOSENSORY_BEHAVIOR, chr1p34, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, GOBP_SENSORY_PERCEPTION, REACTOME_GAP_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION, P53_DECAMER_Q2, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (6): cell-cell signaling (GO:0007267), sensory perception of smell (GO:0007608), olfactory behavior (GO:0042048), gap junction-mediated intercellular transport (GO:1990349), 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 (8): nucleoplasm (GO:0005654), nucleolus (GO:0005730), plasma membrane (GO:0005886), connexin complex (GO:0005922), cell junction (GO:0030054), gap junction (GO:0005921), 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 anatomical structure	3
cellular process	2
nuclear lumen	2
cell communication	1
signaling	1
sensory perception of chemical stimulus	1
chemosensory behavior	1
intercellular transport	1
transport	1
wide pore channel activity	1
binding	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
gap junction	1
plasma membrane protein complex	1
cell-cell junction	1
cell junction	1

Protein interactions and networks

STRING

430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GJB4	GJE1	A6NN92	486
GJB4	TJP1	Q07157	419
GJB4	CNST	Q6PJW8	417
GJB4	GJB3	O75712	402
GJB4	KDSR	Q06136	369
GJB4	KRT83	P78385	367
GJB4	KCNQ4	P56696	358
GJB4	VSIG1	Q86XK7	349
GJB4	NIPAL4	Q0D2K0	332
GJB4	LORICRIN	P23490	325
GJB4	PNPLA1	Q8N8W4	323
GJB4	SPINK5	Q9NQ38	321
GJB4	CYP4F22	Q6NT55	320
GJB4	AP1S1	P61966	315
GJB4	KCNJ10	P78508	307

IntAct

29 interactions, top by confidence:

A	B	Type	Score
TMEM11	GJB4	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	GJB4	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	GJB4	psi-mi:“MI:0915”(physical association)	0.560
KLRC1	GJB4	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	GJB4	psi-mi:“MI:0915”(physical association)	0.560
ARLN	GJB4	psi-mi:“MI:0915”(physical association)	0.560
TM4SF4	GJB4	psi-mi:“MI:0915”(physical association)	0.560
LHFPL5	GJB4	psi-mi:“MI:0915”(physical association)	0.560
COMT	GJB4	psi-mi:“MI:0915”(physical association)	0.560
GJB4	PSME1	psi-mi:“MI:0915”(physical association)	0.400
GJB4	KLRC1	psi-mi:“MI:0915”(physical association)	0.000
ARLN	GJB4	psi-mi:“MI:0915”(physical association)	0.000
TM4SF4	GJB4	psi-mi:“MI:0915”(physical association)	0.000
LHFPL5	GJB4	psi-mi:“MI:0915”(physical association)	0.000
COMT	GJB4	psi-mi:“MI:0915”(physical association)	0.000
TMEM218	GJB4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): PSME1 (Affinity Capture-MS), GJB4 (Two-hybrid), GJB4 (Two-hybrid), GJB4 (Two-hybrid), GJB4 (Two-hybrid), GJB4 (Two-hybrid), GJB4 (Two-hybrid), GJB4 (Two-hybrid), GJB4 (Two-hybrid), LHFPL5 (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	78
Likely benign	14
Benign	22

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
5005	NM_153212.3(GJB4):c.411C>A (p.Phe137Leu)	Pathogenic
5006	NM_153212.3(GJB4):c.253A>C (p.Thr85Pro)	Pathogenic
5007	NM_153212.3(GJB4):c.35G>A (p.Gly12Asp)	Pathogenic
5009	NM_153212.3(GJB4):c.566T>A (p.Phe189Tyr)	Pathogenic
4822944	NM_153212.3(GJB4):c.411C>G (p.Phe137Leu)	Likely pathogenic
5004	NM_153212.3(GJB4):c.409T>C (p.Phe137Leu)	Likely pathogenic

SpliceAI

291 predictions. Top by Δscore:

Variant	Effect	Δscore
1:34759836:C:G	donor_gain	0.9900
1:34759784:GAAGG:G	donor_gain	0.9800
1:34759787:GG:G	donor_gain	0.9800
1:34759788:GG:G	donor_gain	0.9800
1:34759821:G:GT	donor_gain	0.9800
1:34759841:C:G	donor_gain	0.9800
1:34761355:T:A	acceptor_gain	0.9700
1:34759857:G:T	donor_gain	0.9600
1:34759846:G:GT	donor_gain	0.9400
1:34759764:G:GT	donor_gain	0.9200
1:34761334:T:TA	acceptor_gain	0.9000
1:34759771:C:G	donor_gain	0.8900
1:34759787:GGGT:G	donor_loss	0.8900
1:34759789:GTG:G	donor_loss	0.8900
1:34759790:T:A	donor_loss	0.8900
1:34759791:GAG:G	donor_loss	0.8900
1:34759856:GGACC:G	donor_gain	0.8900
1:34759865:G:GT	donor_gain	0.8800
1:34761348:C:CA	acceptor_gain	0.8700
1:34759789:G:GG	donor_gain	0.8600
1:34761274:A:AG	acceptor_gain	0.8400
1:34761275:G:GG	acceptor_gain	0.8400
1:34761350:T:TA	acceptor_gain	0.8400
1:34759884:G:GT	donor_gain	0.8300
1:34761274:AG:A	acceptor_gain	0.8300
1:34761275:GG:G	acceptor_gain	0.8300
1:34759885:G:T	donor_gain	0.8200
1:34760931:A:AG	acceptor_gain	0.8200
1:34760932:G:GG	acceptor_gain	0.8200
1:34761270:CTGCA:C	acceptor_loss	0.8200

AlphaMissense

1730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:34761406:T:G	F51C	0.983
1:34761654:A:C	S134R	0.980
1:34761656:C:A	S134R	0.980
1:34761656:C:G	S134R	0.980
1:34761386:G:C	W44C	0.979
1:34761386:G:T	W44C	0.979
1:34761687:T:C	F145L	0.978
1:34761689:C:A	F145L	0.978
1:34761689:C:G	F145L	0.978
1:34761405:T:C	F51L	0.977
1:34761407:T:A	F51L	0.977
1:34761407:T:G	F51L	0.977
1:34761411:T:A	C53S	0.976
1:34761412:G:C	C53S	0.976
1:34761459:T:C	F69L	0.976
1:34761461:C:A	F69L	0.976
1:34761461:C:G	F69L	0.976
1:34761432:T:A	C60S	0.975
1:34761433:G:C	C60S	0.975
1:34761803:G:C	K183N	0.975
1:34761803:G:T	K183N	0.975
1:34761810:T:C	F186L	0.975
1:34761812:C:A	F186L	0.975
1:34761812:C:G	F186L	0.975
1:34761668:G:C	K138N	0.973
1:34761668:G:T	K138N	0.973
1:34761777:T:A	C175S	0.973
1:34761778:G:C	C175S	0.973
1:34761510:T:C	C86R	0.972
1:34761779:T:G	C175W	0.972

dbSNP variants (sampled 300 via entrez): RS1001461932 (1:34758874 G>A), RS1001855463 (1:34762480 T>C), RS1002285981 (1:34760759 G>A,C), RS1002408442 (1:34762679 G>A), RS1003541680 (1:34760153 G>A,T), RS1004014627 (1:34759890 A>G), RS1004292385 (1:34762377 GGA>G), RS1006339921 (1:34758218 G>A), RS1006416307 (1:34762109 G>A), RS1006863476 (1:34760108 C>A,T), RS1007388960 (1:34759771 C>T), RS1007740154 (1:34762334 A>C), RS1008393310 (1:34760710 T>C), RS1008652379 (1:34761084 T>A,C,G), RS1009849489 (1:34759925 G>A)

Disease associations

OMIM: gene MIM:605425 | disease phenotypes: MIM:617524, MIM:220290, MIM:601544, MIM:133200

GenCC curated gene-disease

Disease	Classification	Inheritance
erythrokeratodermia variabilis et progressiva 2	Strong	Autosomal dominant
erythrokeratodermia variabilis	Supportive	Autosomal dominant

Mondo (5): erythrokeratodermia variabilis et progressiva 2 (MONDO:0033012), autosomal recessive nonsyndromic hearing loss 1A (MONDO:0009076), autosomal dominant nonsyndromic hearing loss 3A (MONDO:0011103), erythrokeratodermia variabilis et progressiva 1 (MONDO:0033010), erythrokeratodermia variabilis (MONDO:0017851)

Orphanet (3): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Erythrokeratodermia variabilis (Orphanet:317)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000035	Abnormal testis morphology
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000411	Protruding ear
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000819	Diabetes mellitus
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000988	Skin rash
HP:0000992	Cutaneous photosensitivity
HP:0000998	Hypertrichosis
HP:0001034	Hypermelanotic macule
HP:0001156	Brachydactyly
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001595	Abnormal hair morphology
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology
HP:0001824	Weight loss
HP:0002230	Generalized hirsutism
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0005588	Patchy palmoplantar hyperkeratosis
HP:0007400	Irregular hyperpigmentation
HP:0007957	Corneal opacity
HP:0008066	Abnormal blistering of the skin
HP:0008069	Neoplasm of the skin

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009612_3	Triglyceride levels x thiazide or thiazide-like diuretics use interaction	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D056266	Erythrokeratodermia Variabilis	C16.320.850.337; C17.800.229.606; C17.800.428.304; C17.800.827.337
C567277	Deafness, Autosomal Dominant 3A (supp.)
C567134	Deafness, Autosomal Recessive 1A (supp.)
C536154	Keratoderma palmoplantaris transgrediens (supp.)

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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
beta-lapachone	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Mustard Gas	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05402813	Not specified	RECRUITING	Natural History in Children up to 16 Years With Mild to Profound Hearing Loss Due to Mutations in GJB2 / OTOF Genes