GJB2

Summary

GJB2 (gap junction protein beta 2, HGNC:4284) is a protein-coding gene on chromosome 13q12.11, encoding Gap junction beta-2 protein (P29033). Structural component of gap junctions.

This gene encodes a member of the gap junction protein family (gap junction beta 2) but is more commonly known as connexin 26. The gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels that facilitate the transfer of ions and small molecules between cells. Connexins form hexameric channels in the plasma membrane which regulate passage of ions and small molecules between the cell and its environment or, when joined with another cell, form a dodecameric intercellular gap junction channel. The connexin proteins are grouped into alpha, beta, and gamma subfamilies. Mutations in this gene are responsible for as much as 50% of pre-lingual, recessive deafness.

Source: NCBI Gene 2706 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +11 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 659 total — 112 pathogenic, 85 likely-pathogenic
• Phenotypes (HPO): 113
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004004

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4284
Approved symbol	GJB2
Name	gap junction protein beta 2
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Aliases	CX26, NSRD1
Ensembl gene	ENSG00000165474
Ensembl biotype	protein_coding
OMIM	121011
Entrez	2706

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000382844, ENST00000382848, ENST00000906230, ENST00000906231, ENST00000906232, ENST00000906233, ENST00000906234, ENST00000906235, ENST00000906236, ENST00000957350

RefSeq mRNA: 1 — MANE Select: NM_004004 NM_004004

CCDS: CCDS9290

Canonical transcript exons

ENST00000382848 — 2 exons

Exon	Start	End
ENSE00001093399	20192783	20192938
ENSE00001493557	20187470	20189603

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 99.73.

FANTOM5 (CAGE): breadth broad, TPM avg 24.1299 / max 2667.0298, expressed in 676 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136336	24.1299	676

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	99.73	gold quality
gingiva	UBERON:0001828	99.72	gold quality
penis	UBERON:0000989	99.58	gold quality
lower esophagus mucosa	UBERON:0035834	99.52	gold quality
pharyngeal mucosa	UBERON:0000355	99.34	gold quality
upper arm skin	UBERON:0004263	99.22	gold quality
body of tongue	UBERON:0011876	99.04	gold quality
oral cavity	UBERON:0000167	98.98	gold quality
esophagus mucosa	UBERON:0002469	98.87	gold quality
mammalian vulva	UBERON:0000997	98.68	gold quality
esophagus squamous epithelium	UBERON:0006920	98.57	gold quality
tongue	UBERON:0001723	95.88	gold quality
upper leg skin	UBERON:0004262	95.48	gold quality
pancreatic ductal cell	CL:0002079	92.67	silver quality
zone of skin	UBERON:0000014	92.63	gold quality
skin of abdomen	UBERON:0001416	92.44	gold quality
skin of leg	UBERON:0001511	92.23	gold quality
ileal mucosa	UBERON:0000331	92.06	gold quality
mucosa of transverse colon	UBERON:0004991	91.92	gold quality
trigeminal ganglion	UBERON:0001675	91.90	gold quality
parotid gland	UBERON:0001831	91.70	gold quality
tonsil	UBERON:0002372	91.39	gold quality
colonic mucosa	UBERON:0000317	91.36	gold quality
superior surface of tongue	UBERON:0007371	91.20	gold quality
vagina	UBERON:0000996	90.92	gold quality
skin of hip	UBERON:0001554	90.89	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.53	gold quality
nasal cavity epithelium	UBERON:0005384	88.96	silver quality
right lobe of liver	UBERON:0001114	87.85	gold quality
mouth mucosa	UBERON:0003729	87.82	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-10	yes	1485.20
E-MTAB-8142	yes	1192.33
E-HCAD-1	yes	256.21
E-CURD-114	yes	62.13
E-MTAB-10596	no	1555.10
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHA15, ESR1, MYB, PAX3, SP1, TFAP2A, ZEB2

miRNA regulators (miRDB)

77 targeting GJB2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-3975	99.62	65.97	697

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• M34T variant in deafness (PMID:11432967)
• mutational analysis in patients with hereditary hearing impairment (PMID:11438992)
• mutations causing sensorineural hearing impairment in Ghana (PMID:11439000)
• prevalence of the 30delG mutation and report of two novel mutations in patients with autosomal recessive non-syndromic hearing loss in Lebanon (PMID:11584050)
• founder deletion mutation in GJB6 cooperating with a GJB2 mutation in Ashkenazi Jews with non-syndromic deafness (PMID:11668644)
• outer hair cell function is affected by the 35delG mutation in Cx26. (PMID:11788203)
• Methylation-sensitive single-stranded conformation analysis showed variable methylation in the promoter region CpG island in 11 out of 20 (55%) breast cancer patients (PMID:11872627)
• Transfection with Cx26 cDNA inhibited dedifferentiation, suppressed cell proliferation, and apoptosis was induced. Tumor growth of PLC/Cx26 was retarded. (PMID:11872644)
• Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. (PMID:11912510)
• Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East. (PMID:11935342)
• Effective rehabilitation for profoundly deaf individuals with GJB2-related deafness is possible through cochlear implantation. (PMID:11977173)
• overexpression of Cx43 or Cx26 in breast cancer cells down-regulated fibroblast growth factor receptor-3 (PMID:12042301)
• Data indicate that, at least in vitro, connexin26 affects the function of human keratinocytes, independently of obvious changes in coupling. (PMID:12064627)
• These results provide evidence as to how heterozygous connexin 26 (cx26) mutations could contribute to autosomal dominant deafness, by resulting in a net loss, and/or alteration, of Cx26 function. (PMID:12064630)
• Frequency of the 35delG mutation of the connexin 26 gene (GJB2) in patients with non-syndromic autosome-recessive deafness from Bashkortostan and in ethnic groups of the Volga-Ural region (PMID:12068628)
• analysis of mutations in the GJB2 gene in Brazilian families with either familial or sporadic deafness in order to determine the frequency and type of connexin26 mutations among patients with non-syndromic hearing loss (PMID:12081719)
• mutations in the Cx26 gene in cases of familial and sporadic hearing loss by gene sequencing and identifies the allelic frequency of the most common mutation leading to HL (35delG) in the population of Eastern Austria (PMID:12107817)
• conformational changes in surface structures of connexin 26 gap junctions (PMID:12110573)
• Mutations found for prelingual deafness in Taiwan (PMID:12111646)
• A novel connexin 26 compound heterozygous mutation results in deafness. (PMID:12169891)
• epidemiology studies of the alleles of GJB2, prevalence rates, genotype-phenotype relations, contribution to the incidence of hearing loss, and other issues related to the clinical validity of genetic testing for GJB2 [review] (PMID:12172392)
• frequency of GJB2 mutations in an Italian population affected by hearing loss, and functional analysis of six missense mutations (PMID:12176036)
• Progressive hearing loss, and recurrent sudden sensorineural hearing loss associated with GJB2 mutations in Austria. (PMID:12189487)
• connexin 26 deafness mutations affect the function of gap junction channels (PMID:12189493)
• Connexin 26 gene mutation is implicated in preverbal hearing impairment. (PMID:12212857)
• roles of Met-34, Cys-64, and Arg-75 in assembly (PMID:12384501)
• prevalence of mutation being responsible for commonest form of non-syndromic recessive deafness in Chinese population (PMID:12384781)
• GJB2 gene mutations are responsible for deafness. (PMID:12393046)
• These findings suggest that expression of Cx26 and Cx43 might be related to the differentiation of the arachnoid villi and meningiomas, and exhibit the different origin of various subtypes of meningiomas. (PMID:12484567)
• Detection of disequilibrium between M34T (c.101T>C) and -493del10 in German hearing impaired persons. (PMID:12497637)
• Loss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness. (PMID:12505163)
• The connexin26 gene is responsible for DFNB1 and DFNA3 (Autosomal Recessive Hereditary Nonsyndromic Deafness Locus 1 and Autosomal Dominant Hereditary Nonsyndromic Deafness Locus 3) (PMID:12522692)
• Mutations may impact outer hair cell function among carriers of one or two mutations. Inner hair cells /nerve impairment among homozygotes and compound heterozygotes is variable. (PMID:12527132)
• Sensorineural deafness may be the result of 35delG mutation in the GJB2 gene. (PMID:12530196)
• The expression of the tumor suppressor gene connexin 26 is not mediated by methylation in human esophageal cancer cells. (PMID:12557263)
• Results were consistent with inheritance of the 235delC mutation from a common ancestor: implications for genetic diagnostic testing for deafness in the Japanese population. (PMID:12560944)
• GJB2 gene is implicated in large vestibular aqueduct syndrome. (PMID:12624506)
• We suggest that cx26 and cx30 form heteromeric connexons in vivo, within the inner ear, with particular properties essential for hearing. (PMID:12668604)
• We identified two single-nucleotide polymorphisms (SNPs) immediately upstream of the first exon of GJB2. (PMID:12684873)
• contribution of mutations and founder effect to non-syndromic hearing loss in India (PMID:12746422)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gjb8	ENSDARG00000042707
mus_musculus	Gjb2	ENSMUSG00000046352
rattus_norvegicus	Gjb2	ENSRNOG00000008855

Paralogs (20): GJA8 (ENSG00000121634), GJB6 (ENSG00000121742), GJA3 (ENSG00000121743), GJA9 (ENSG00000131233), GJA10 (ENSG00000135355), GJA1 (ENSG00000152661), GJD2 (ENSG00000159248), GJB7 (ENSG00000164411), GJB1 (ENSG00000169562), GJC3 (ENSG00000176402), GJD4 (ENSG00000177291), GJC1 (ENSG00000182963), GJD3 (ENSG00000183153), GJA4 (ENSG00000187513), GJB3 (ENSG00000188910), GJB5 (ENSG00000189280), GJB4 (ENSG00000189433), GJC2 (ENSG00000198835), GJE1 (ENSG00000203733), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction beta-2 protein — P29033 (reviewed: P29033)

Alternative names: Connexin-26

All UniProt accessions (2): P29033, H9U1J4

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. Interacts with CNST. Forms heteromeric channels with GJB4.

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

Disease relevance. Deafness, autosomal recessive, 1A (DFNB1A) [MIM:220290] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 3A (DFNA3A) [MIM:601544] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Vohwinkel syndrome (VOWNKL) [MIM:124500] An autosomal dominant disease characterized by hyperkeratosis, constriction on fingers and toes and congenital deafness. The disease is caused by variants affecting the gene represented in this entry. Keratoderma, palmoplantar, with deafness (PPKDFN) [MIM:148350] An autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness. The disease is caused by variants affecting the gene represented in this entry. Keratitis-ichthyosis-deafness syndrome, autosomal dominant (KIDAD) [MIM:148210] An autosomal dominant form of keratitis-ichthyosis-deafness syndrome, a disease characterized by the association of hyperkeratotic skin lesions with vascularizing keratitis and profound sensorineural hearing loss. Clinical features include deafness, ichthyosis, photophobia, absent or decreased eyebrows, sparse or absent scalp hair, decreased sweating and dysplastic finger and toenails. The disease is caused by variants affecting the gene represented in this entry. Bart-Pumphrey syndrome (BAPS) [MIM:149200] An autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability. The disease is caused by variants affecting the gene represented in this entry. Ichthyosis hystrix-like with deafness syndrome (HID syndrome) [MIM:602540] An autosomal dominant keratinizing disorder characterized by sensorineural deafness and spiky hyperkeratosis affecting the entire skin. HID syndrome is considered to differ from the similar KID syndrome in the extent and time of occurrence of skin symptoms and the severity of the associated keratitis. 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_003995* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000500	Connexin	Family
IPR002268	Connexin26	Family
IPR013092	Connexin_N	Domain
IPR017990	Connexin_CS	Conserved_site
IPR019570	Connexin_CCC	Domain
IPR038359	Connexin_N_sf	Homologous_superfamily

Pfam: PF00029

UniProt features (106 total): sequence variant 67, helix 8, strand 6, topological domain 5, transmembrane region 4, turn 3, binding site 3, disulfide bond 3, mutagenesis site 3, sequence conflict 2, chain 1, intramembrane region 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
7QEQ	ELECTRON MICROSCOPY	1.9
7QEY	ELECTRON MICROSCOPY	2
7QET	ELECTRON MICROSCOPY	2.1
7QEW	ELECTRON MICROSCOPY	2.1
7QER	ELECTRON MICROSCOPY	2.2
8QA0	ELECTRON MICROSCOPY	2.3
8QA1	ELECTRON MICROSCOPY	2.3
8QA2	ELECTRON MICROSCOPY	2.3
8QA3	ELECTRON MICROSCOPY	2.3
8Q9Z	ELECTRON MICROSCOPY	2.4
7QES	ELECTRON MICROSCOPY	2.6
7QEU	ELECTRON MICROSCOPY	2.7
7QEO	ELECTRON MICROSCOPY	2.9
7QEV	ELECTRON MICROSCOPY	2.9
5ER7	X-RAY DIFFRACTION	3.29
2ZW3	X-RAY DIFFRACTION	3.5
5ERA	X-RAY DIFFRACTION	3.8
6UVR	ELECTRON MICROSCOPY	4
6UVS	ELECTRON MICROSCOPY	4.2
3IZ1	ELECTRON CRYSTALLOGRAPHY	6
6UVT	ELECTRON MICROSCOPY	7.5
3IZ2	ELECTRON CRYSTALLOGRAPHY	10
5KJ3	SOLUTION NMR
5KJG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29033-F1	86.35	0.51

Functional residue map

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

Ligand- & substrate-binding residues (3): 42 (in other chain); 45; 47

Disulfide bonds (3): 53–180, 60–174, 64–169

Mutagenesis-validated functional residues (3):

Position	Phenotype
2–10	strongly reduced insertion into the cell membrane and strongly reduced gap junction plaque assembly.
2–7	loss of gap junction ion conductance.
34	loss of gap junction ion conductance, probably due to very low open probability of the channels. can form functional cha

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-190704	Oligomerization of connexins into connexons
R-HSA-190827	Transport of connexins along the secretory pathway
R-HSA-190861	Gap junction assembly
R-HSA-190872	Transport of connexons to the plasma membrane

MSigDB gene sets: 422 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, MODULE_92, BENPORATH_ES_WITH_H3K27ME3, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, DARWICHE_PAPILLOMA_PROGRESSION_RISK, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELL_CELL_SIGNALING, COUP_01, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_EAR_DEVELOPMENT

GO Biological Process (7): cell-cell signaling (GO:0007267), sensory perception of sound (GO:0007605), gap junction assembly (GO:0016264), transmembrane transport (GO:0055085), gap junction-mediated intercellular transport (GO:1990349), cell communication (GO:0007154), cell communication by electrical coupling (GO:0010644)

GO Molecular Function (6): gap junction channel activity (GO:0005243), calcium ion binding (GO:0005509), identical protein binding (GO:0042802), gap junction channel activity involved in cell communication by electrical coupling (GO:1903763), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), 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-2 pathways:

Category	Pathways
Gap junction assembly	3
Gap junction trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
cellular process	2
signaling	1
sensory perception of mechanical stimulus	1
cell-cell junction assembly	1
transport	1
intercellular transport	1
wide pore channel activity	1
metal ion binding	1
protein binding	1
gap junction channel activity	1
cell communication by electrical coupling	1
binding	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	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

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GJB2	GJB1	P08034	984
GJB2	GJB6	O95452	981
GJB2	SLC26A4	O43511	961
GJB2	NANOG	Q9H9S0	914
GJB2	MYO15A	Q9UKN7	913
GJB2	TMIE	Q8NEW7	896
GJB2	GJA5	P36382	888
GJB2	OTOF	Q9HC10	876
GJB2	GJA1	P17302	864
GJB2	MYO7A	P78427	842
GJB2	TMC1	Q8TDI8	787
GJB2	ESPN	B1AK53	785
GJB2	CDH23	Q9H251	770
GJB2	PANX1	Q96RD7	746
GJB2	WFS1	O76024	745

IntAct

123 interactions, top by confidence:

A	B	Type	Score
GJB2	GJB2	psi-mi:“MI:0407”(direct interaction)	0.690
GJB2	GJB1	psi-mi:“MI:0915”(physical association)	0.560
GJB2	LRRC4C	psi-mi:“MI:0915”(physical association)	0.560
GJB2	TBXA2R	psi-mi:“MI:0915”(physical association)	0.560
GJB2	TEX29	psi-mi:“MI:0915”(physical association)	0.560
GJB2	GJA5	psi-mi:“MI:0915”(physical association)	0.560
GJB2	GPR42	psi-mi:“MI:0915”(physical association)	0.560
GJB2	AQP6	psi-mi:“MI:0915”(physical association)	0.560
GJB2	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
GJB2	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
GJB2	TMEM106A	psi-mi:“MI:0915”(physical association)	0.560
KLRC1	GJB2	psi-mi:“MI:0915”(physical association)	0.560
	GJB2	psi-mi:“MI:0915”(physical association)	0.560
GJB2	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
GJB2	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
GJB2	SHISAL1	psi-mi:“MI:0915”(physical association)	0.560
GPR42	GJB2	psi-mi:“MI:0915”(physical association)	0.560
GJB2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
FFAR2	GJB2	psi-mi:“MI:0915”(physical association)	0.560
GJB2	TRHR	psi-mi:“MI:0915”(physical association)	0.560
GJB2	GPR152	psi-mi:“MI:0915”(physical association)	0.560
GJB2	MFSD6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (68): GJB2 (Two-hybrid), PSMD2 (Affinity Capture-MS), TFRC (Affinity Capture-MS), SNX3 (Affinity Capture-MS), PIEZO1 (Affinity Capture-MS), INADL (Affinity Capture-MS), RAB11FIP2 (Affinity Capture-MS), PACSIN3 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), MUC13 (Affinity Capture-MS), ACKR3 (Affinity Capture-MS), CLSPN (Affinity Capture-MS), SLC35E1 (Affinity Capture-MS), ANTXR1 (Affinity Capture-MS), GJB2 (Two-hybrid)

ESM2 similar proteins: A2VE67, A4FUN9, A6NN92, O18968, O54851, O70610, O75712, O93533, O95377, O95452, P08033, P08034, P08983, P16864, P21994, P25305, P28230, P28231, P28232, P28233, P29033, P36380, P46691, P51915, P51916, P69998, P69999, P70689, Q00977, Q02738, Q02739, Q03190, Q0V990, Q29559, Q58D78, Q5E9Z5, Q60HF7, Q6PEY0, Q6S5G4, Q6WGK6

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

3 interactions.

A	Effect	B	Mechanism
DNM2	down-regulates	GJB2	binding
ZEB2	“down-regulates quantity by repression”	GJB2	“transcriptional regulation”
GJB2	down-regulates	Epithelial-mesenchymal_transition

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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
Gap junction assembly	5	63.7×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
cell-cell signaling	6	9.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	112
Likely pathogenic	85
Uncertain significance	187
Likely benign	126
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068780	NM_004004.6(GJB2):c.53_63del (p.Thr18fs)	Pathogenic
1076706	NM_004004.6(GJB2):c.200dup (p.His67fs)	Pathogenic
1076708	NM_004004.6(GJB2):c.268del (p.Leu89_Leu90insTer)	Pathogenic
1202621	NM_004004.6(GJB2):c.79_82delinsAGA (p.Val27fs)	Pathogenic
1297075	NM_004004.6(GJB2):c.157T>A (p.Cys53Ser)	Pathogenic
1297076	NM_004004.6(GJB2):c.232G>A (p.Ala78Thr)	Pathogenic
1298565	NM_004004.6(GJB2):c.592G>A (p.Val198Met)	Pathogenic
1357104	NM_004004.6(GJB2):c.407dup (p.Tyr136Ter)	Pathogenic
1451382	NM_004004.6(GJB2):c.76del (p.Thr26fs)	Pathogenic
1454400	NM_004004.6(GJB2):c.624del (p.Glu209fs)	Pathogenic
1458345	NM_004004.6(GJB2):c.402del (p.Trp133_Trp134insTer)	Pathogenic
1458348	NM_004004.6(GJB2):c.263C>T (p.Ala88Val)	Pathogenic
158605	NM_004004.6(GJB2):c.132G>A (p.Trp44Ter)	Pathogenic
158606	NM_004004.6(GJB2):c.158G>A (p.Cys53Tyr)	Pathogenic
158607	NM_004004.6(GJB2):c.298C>T (p.His100Tyr)	Pathogenic
167134	NM_004004.6(GJB2):c.250G>T (p.Val84Leu)	Pathogenic
17000	NM_004004.6(GJB2):c.101T>C (p.Met34Thr)	Pathogenic
17001	NM_004004.6(GJB2):c.231G>A (p.Trp77Ter)	Pathogenic
17002	NM_004004.6(GJB2):c.71G>A (p.Trp24Ter)	Pathogenic
17004	NM_004004.6(GJB2):c.35del (p.Gly12fs)	Pathogenic
17005	NM_004004.6(GJB2):c.139G>T (p.Glu47Ter)	Pathogenic
17006	NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del)	Pathogenic
17007	NM_004004.6(GJB2):c.551G>C (p.Arg184Pro)	Pathogenic
17009	NM_004004.6(GJB2):c.427C>T (p.Arg143Trp)	Pathogenic
17010	NM_004004.6(GJB2):c.167del (p.Leu56fs)	Pathogenic
17011	NM_004004.6(GJB2):c.223C>T (p.Arg75Trp)	Pathogenic
17012	NM_004004.6(GJB2):c.196G>C (p.Asp66His)	Pathogenic
17014	NM_004004.6(GJB2):c.235del (p.Leu79fs)	Pathogenic
17016	NM_004004.6(GJB2):c.269T>C (p.Leu90Pro)	Pathogenic
17020	NM_004004.6(GJB2):c.148G>A (p.Asp50Asn)	Pathogenic

SpliceAI

404 predictions. Top by Δscore:

Variant	Effect	Δscore
13:20192778:CTCA:C	donor_loss	1.0000
13:20192779:TCA:T	donor_loss	1.0000
13:20192780:CAC:C	donor_loss	1.0000
13:20192782:C:CA	donor_loss	1.0000
13:20192777:GCTCA:G	donor_loss	0.9900
13:20192782:CCTG:C	donor_gain	0.9900
13:20189599:TTGCT:T	acceptor_gain	0.9800
13:20189604:C:CC	acceptor_gain	0.9800
13:20192781:A:AC	donor_gain	0.9800
13:20192782:C:CC	donor_gain	0.9800
13:20189480:CATAA:C	acceptor_gain	0.9700
13:20189602:CT:C	acceptor_gain	0.9700
13:20189600:TGCT:T	acceptor_gain	0.9600
13:20190772:TTTCC:T	donor_gain	0.9300
13:20189638:CTAG:C	acceptor_gain	0.9200
13:20189600:TGCTC:T	acceptor_loss	0.9100
13:20189601:GCT:G	acceptor_gain	0.9100
13:20189601:GCTCT:G	acceptor_loss	0.9100
13:20189602:CTC:C	acceptor_gain	0.9100
13:20189603:TCT:T	acceptor_gain	0.9100
13:20189603:TCTGG:T	acceptor_loss	0.9100
13:20189604:CT:C	acceptor_loss	0.9100
13:20189605:T:A	acceptor_loss	0.9100
13:20189617:A:C	acceptor_loss	0.9100
13:20189604:C:G	acceptor_gain	0.8800
13:20192048:T:TA	donor_gain	0.8700
13:20190771:TTTTC:T	donor_gain	0.8300
13:20190834:T:A	donor_gain	0.8200
13:20192749:T:TA	donor_gain	0.8100
13:20190802:T:TA	donor_gain	0.8000

AlphaMissense

1493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:20189018:C:A	K188N	0.999
13:20189018:C:G	K188N	0.999
13:20189039:A:C	F181L	0.999
13:20189039:A:T	F181L	0.999
13:20189041:A:G	F181L	0.999
13:20189042:G:C	C180W	0.999
13:20189043:C:G	C180S	0.999
13:20189043:C:T	C180Y	0.999
13:20189044:A:G	C180R	0.999
13:20189044:A:T	C180S	0.999
13:20189060:A:C	C174W	0.999
13:20189390:G:C	C64W	0.999
13:20189391:C:G	C64S	0.999
13:20189391:C:T	C64Y	0.999
13:20189392:A:T	C64S	0.999
13:20189403:C:G	C60S	0.999
13:20189404:A:T	C60S	0.999
13:20189423:G:C	C53W	0.999
13:20189424:C:G	C53S	0.999
13:20189424:C:T	C53Y	0.999
13:20189425:A:G	C53R	0.999
13:20189425:A:T	C53S	0.999
13:20189450:C:A	W44C	0.999
13:20189450:C:G	W44C	0.999
13:20189452:A:G	W44R	0.999
13:20189452:A:T	W44R	0.999
13:20189031:C:G	R184P	0.998
13:20189040:A:C	F181C	0.998
13:20189043:C:A	C180F	0.998
13:20189061:C:G	C174S	0.998

dbSNP variants (sampled 300 via entrez): RS1000051859 (13:20191015 A>C), RS1000083899 (13:20190767 T>A,C), RS1000548264 (13:20187422 G>A), RS1000879130 (13:20190804 CTTCT>C), RS1001097388 (13:20191059 C>A), RS1001547614 (13:20190525 C>T), RS1001880027 (13:20191856 C>T), RS1001912718 (13:20191465 A>G), RS1002228316 (13:20191395 A>C,T), RS1002957926 (13:20193850 T>C), RS1003116265 (13:20189103 C>T), RS1003447976 (13:20187683 A>G), RS1003660637 (13:20189251 T>C), RS1003698917 (13:20192822 C>A), RS1003897765 (13:20194439 C>G,T)

Disease associations

OMIM: gene MIM:121011 | disease phenotypes: MIM:220290, MIM:124500, MIM:148210, MIM:148350, MIM:149200, MIM:304400, MIM:601544, MIM:602540, MIM:612645, MIM:607197, MIM:128600, MIM:616515, MIM:601386, MIM:129500, MIM:612643, MIM:308205, MIM:163950

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss disorder	Definitive	Autosomal dominant
nonsyndromic genetic hearing loss	Definitive	Autosomal recessive
keratoderma hereditarium mutilans	Definitive	Autosomal dominant
palmoplantar keratoderma-deafness syndrome	Definitive	Autosomal dominant
Bart-Pumphrey syndrome	Definitive	Autosomal dominant
ichthyosis, hystrix-like, with hearing loss	Definitive	Autosomal dominant
autosomal recessive nonsyndromic hearing loss 1A	Definitive	Autosomal recessive
autosomal dominant keratitis-ichthyosis-hearing loss syndrome	Strong	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 3A	Strong	Autosomal dominant
KID syndrome	Supportive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AR
hearing loss disorder	Definitive	AD

Mondo (25): autosomal recessive nonsyndromic hearing loss 1A (MONDO:0009076), hearing loss disorder (MONDO:0005365), keratoderma hereditarium mutilans (MONDO:0007422), autosomal dominant keratitis-ichthyosis-hearing loss syndrome (MONDO:0007850), palmoplantar keratoderma-deafness syndrome (MONDO:0007852), Bart-Pumphrey syndrome (MONDO:0007866), X-linked mixed hearing loss with perilymphatic gusher (MONDO:0010576), autosomal dominant nonsyndromic hearing loss 3A (MONDO:0011103), ichthyosis, hystrix-like, with hearing loss (MONDO:0011245), nonsyndromic genetic hearing loss (MONDO:0019497), autosomal recessive nonsyndromic hearing loss 1B (MONDO:0012977), hearing loss, autosomal recessive (MONDO:0019588), sensorineural hearing loss disorder (MONDO:0020678), hereditary palmoplantar keratoderma (MONDO:0019272), intellectual disability (MONDO:0001071)

Orphanet (16): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Palmoplantar keratoderma-deafness syndrome (Orphanet:2202), Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome (Orphanet:2698), X-linked mixed deafness with perilymphatic gusher (Orphanet:383), KID syndrome (Orphanet:477), Keratoderma hereditarium mutilans (Orphanet:494), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare non-syndromic genetic deafness (Orphanet:87884), Rare genetic deafness (Orphanet:96210), Hereditary palmoplantar keratoderma (Orphanet:79357), Hidrotic ectodermal dysplasia (Orphanet:189), Ichthyosis follicularis-alopecia-photophobia syndrome (Orphanet:2273), BRESEK syndrome (Orphanet:85284), Noonan syndrome (Orphanet:648), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

113 total (30 of 113 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000221	Furrowed tongue
HP:0000230	Gingivitis
HP:0000365	Hearing impairment
HP:0000381	Stapes ankylosis
HP:0000399	Prelingual sensorineural hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000491	Keratitis
HP:0000495	Recurrent corneal erosions
HP:0000509	Conjunctivitis
HP:0000559	Corneal scarring
HP:0000561	Absent eyelashes
HP:0000572	Visual loss
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000653	Sparse eyelashes
HP:0000691	Microdontia
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0001019	Erythroderma
HP:0001097	Keratoconjunctivitis sicca

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004729_1	Facial emotion recognition (happy faces)	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008329	facial emotion recognition measurement

MeSH disease descriptors (15)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C567277	Deafness, Autosomal Dominant 3A (supp.)
C567215	Deafness, Autosomal Dominant 3B (supp.)
C564609	Deafness, Autosomal Recessive (supp.)
C563327	Deafness, Autosomal Recessive 12 (supp.)
C567134	Deafness, Autosomal Recessive 1A (supp.)
C567213	Deafness, Autosomal Recessive 1b (supp.)
C566528	HID Syndrome (supp.)
C536085	Ichthyosis follicularis atrichia photophobia syndrome (supp.)
C536168	Keratitis, Ichthyosis, and Deafness (KID) Syndrome (supp.)
C537210	Knuckle pads, leuconychia and sensorineural deafness (supp.)
C580334	Nonsyndromic Deafness (supp.)
C536152	Palmoplantar Keratoderma with Deafness (supp.)
C536457	Vohwinkel syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295738 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 257,519 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1384	KANAMYCIN	4	257,519

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

ChEMBL bioactivities

11 potent at pChembl≥5 of 22 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.60	IC50	2500	nM	CHEMBL4204676
5.37	IC50	4300	nM	CHEMBL4205159
5.31	IC50	4900	nM	CHEMBL4209017
5.22	IC50	6000	nM	CHEMBL4780949
5.21	IC50	6200	nM	CHEMBL4213413
5.21	IC50	6200	nM	CHEMBL4210911
5.18	IC50	6600	nM	CHEMBL4213933
5.12	IC50	7600	nM	CHEMBL4203134
5.09	IC50	8100	nM	CHEMBL4209535
5.08	IC50	8400	nM	CHEMBL4212437
5.03	IC50	9400	nM	KANAMYCIN

PubChem BioAssay actives

11 with measured affinity, of 74 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-5-[(4-chlorophenyl)methoxy]-6-[(4-chlorophenyl)methoxymethyl]-3-hydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	2.5000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-3-hydroxy-5-[(4-methylphenyl)methoxy]-6-[(4-methylphenyl)methoxymethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	4.3000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-3-hydroxy-5-(naphthalen-2-ylmethoxy)-6-(naphthalen-2-ylmethoxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	4.9000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2S,3R,4S,5S,6R)-4-amino-6-[[4-(1H-benzimidazol-2-yl)phenoxy]methyl]-3,5-dihydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1740925: Inhibition of human Cx26 expressed in Escherichia coli LB2003 cells in medium containing 4 mM K+ and 500 uM IPTG by measuring cell growth after 18 hrs by plate reader	ic50	6.0000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-3-hydroxy-5-[(3-phenylphenyl)methoxy]-6-[(3-phenylphenyl)methoxymethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	6.2000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-5-hexoxy-6-(hexoxymethyl)-3-hydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	6.2000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-3-hydroxy-5-(naphthalen-1-ylmethoxy)-6-(naphthalen-1-ylmethoxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	6.6000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-3-hydroxy-5-phenylmethoxy-6-(phenylmethoxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	7.6000	uM
(2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-4-amino-5-[(4-fluorophenyl)methoxy]-6-[(4-fluorophenyl)methoxymethyl]-3-hydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	8.1000	uM
(1S,3R,4S,5R,6R)-4-[(2R,3R,4S,5S,6R)-4-amino-3-methoxy-5-phenylmethoxy-6-(phenylmethoxymethyl)oxan-2-yl]oxy-6-[(2R,3R,4S,5R,6R)-6-(aminomethyl)-3,4,5-trimethoxyoxan-2-yl]oxy-5-methoxycyclohexane-1,3-diamine	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	8.4000	uM
Kanamycin	1385094: Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	ic50	9.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, increases methylation	4
sodium arsenite	increases expression, affects expression	3
Acetaminophen	decreases expression, affects cotreatment	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Tretinoin	affects cotreatment, increases activity, increases reaction, increases expression	3
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, decreases methylation, decreases reaction	2
chloropicrin	decreases expression, affects expression	2
Calcitriol	decreases expression, increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	decreases expression, affects cotreatment, increases expression	2
Cyclosporine	decreases expression, affects cotreatment	2
Aflatoxin B1	affects expression, decreases expression	2
propionaldehyde	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	decreases expression, affects cotreatment	1
pirinixic acid	increases activity, increases expression, affects binding	1
ethyl-p-hydroxybenzoate	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
oleylamide	affects cotreatment, decreases reaction, increases activity, increases reaction	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression, decreases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
indeno(1,2,3-cd)pyrene	increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
pentanal	increases expression	1
nefazodone	affects cotreatment, decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4199784	Binding	Inhibition of recombinant human Cx26 expressed in Escherichia coli LB2003 assessed as reduction in cell growth measured after 18 hrs	Inhibition of Connexin Hemichannels by New Amphiphilic Aminoglycosides without Antibiotic Activity. — ACS Med Chem Lett

Cellosaurus cell lines

26 cell lines: 11 induced pluripotent stem cell, 10 transformed cell line, 2 embryonic stem cell, 1 cancer cell line, 1 spontaneously immortalized cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4XR	SDQLCHi035-A	Induced pluripotent stem cell	Male
CVCL_A5GK	UMi030-A	Induced pluripotent stem cell	Male
CVCL_BV66	GM23417	Transformed cell line	Male
CVCL_CX81	GM23633	Transformed cell line	Female
CVCL_D1WK	Abcam A-549 GJB2 KO	Cancer cell line	Male
CVCL_D2YN	GM25493	Transformed cell line	Female
CVCL_D2Z7	GM25492	Transformed cell line	Female
CVCL_D9WZ	Ubigene HaCaT GJB2 KO	Spontaneously immortalized cell line	Male
CVCL_F1VG	DUK19946	Transformed cell line	Sex unspecified
CVCL_GT02	GM23835	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss