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GJB5

gene
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Also known as CX31.1

Summary

GJB5 (gap junction protein beta 5, HGNC:4287) is a protein-coding gene on chromosome 1p34.3, encoding Gap junction beta-5 protein (O95377). 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 beta-type (group I) connexin family. The encoded protein is a gap junction protein involved in intercellular communication related to epidermal differentiation and environmental sensing. This gene has been linked to non-small cell lung cancer.

Source: NCBI Gene 2709 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 41 total
  • MANE Select transcript: NM_005268

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:4287
Approved symbolGJB5
Namegap junction protein beta 5
Location1p34.3
Locus typegene with protein product
StatusApproved
AliasesCX31.1
Ensembl geneENSG00000189280
Ensembl biotypeprotein_coding
OMIM604493
Entrez2709

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000338513, ENST00000863284, ENST00000915003

RefSeq mRNA: 1 — MANE Select: NM_005268 NM_005268

CCDS: CCDS382

Canonical transcript exons

ENST00000338513 — 2 exons

ExonStartEnd
ENSE000013680063475504734755195
ENSE000013778303475730734758512

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 95.45.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3523 / max 138.1978, expressed in 227 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
20703.0661217
20710.286389

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
lower esophagus mucosaUBERON:003583495.45gold quality
skin of abdomenUBERON:000141695.19gold quality
esophagus mucosaUBERON:000246994.95gold quality
skin of legUBERON:000151194.58gold quality
zone of skinUBERON:000001493.02gold quality
upper arm skinUBERON:000426390.87gold quality
upper leg skinUBERON:000426288.62gold quality
tongue squamous epitheliumUBERON:000691988.30silver quality
gingivaUBERON:000182888.13gold quality
gingival epitheliumUBERON:000194987.62gold quality
epithelium of esophagusUBERON:000197687.19gold quality
esophagus squamous epitheliumUBERON:000692086.76gold quality
olfactory segment of nasal mucosaUBERON:000538686.10gold quality
oral cavityUBERON:000016785.49gold quality
palpebral conjunctivaUBERON:000181282.36gold quality
squamous epitheliumUBERON:000691482.24gold quality
vaginaUBERON:000099681.79gold quality
mammalian vulvaUBERON:000099781.08gold quality
pharyngeal mucosaUBERON:000035579.62gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047377.76silver quality
cervix epitheliumUBERON:000480177.32gold quality
nippleUBERON:000203075.53gold quality
penisUBERON:000098975.51gold quality
mouth mucosaUBERON:000372974.31gold quality
nasal cavity mucosaUBERON:000182673.72gold quality
minor salivary glandUBERON:000183072.24gold quality
nasal cavity epitheliumUBERON:000538471.34silver quality
gall bladderUBERON:000211071.02gold quality
esophagusUBERON:000104370.98gold quality
skin of hipUBERON:000155469.89gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes11.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting GJB5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6508-5P99.9270.672465
HSA-MIR-1224-5P99.4865.59803
HSA-MIR-219A-1-3P98.9167.87639
HSA-MIR-4477A98.8369.752952
HSA-MIR-4712-3P98.5265.39822
HSA-MIR-365297.7165.431890
HSA-MIR-22-5P97.6768.921355
HSA-MIR-4723-3P97.6765.911017
HSA-MIR-500A-3P97.6067.48595
HSA-MIR-443097.4765.611813
HSA-MIR-6769B-3P97.4165.531036
HSA-MIR-318397.4065.68978
HSA-MIR-10398-5P97.1264.941051

Literature-anchored findings (GeneRIF, showing 4)

  • Overexpression of Cx31.1 in H1299 cells reduced cell proliferation, delayed the G1 phase, inhibited anchorage-independent growth, and suppressed cell migration and invasion. Xenografts of Cx31.1 overexpressing H1299 cells had reduced tumourigenicity. (PMID:21777377)
  • autophagy contributed to Cx31.1 degradation, and clathrin might be involved in the autophagy of Cx31.1. (PMID:25388970)
  • GJB5 association with BRAF mutation and survival in cutaneous malignant melanoma. (PMID:34240406)
  • Cx31.1 can selectively intermix with co-expressed connexins to facilitate its assembly into gap junctions. (PMID:38533727)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriogjb10ENSDARG00000075854
mus_musculusGjb5ENSMUSG00000042357
rattus_norvegicusGjb5ENSRNOG00000059897

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), GJB4 (ENSG00000189433), GJC2 (ENSG00000198835), GJE1 (ENSG00000203733), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction beta-5 protein — O95377 (reviewed: O95377)

Alternative names: Connexin-31.1

All UniProt accessions (2): A0A654IE64, O95377

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.

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

RefSeq proteins (1): NP_005259* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000500ConnexinFamily
IPR002271Connexin311Family
IPR013092Connexin_NDomain
IPR017990Connexin_CSConserved_site
IPR019570Connexin_CCCDomain
IPR038359Connexin_N_sfHomologous_superfamily

Pfam: PF00029

UniProt features (10 total): topological domain 5, transmembrane region 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O95377-F178.610.38

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-190861Gap junction assembly

MSigDB gene sets: 157 (showing top): GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MORF_FLT1, MORF_MSH3, MODULE_45, MORF_BRCA1, RIZKI_TUMOR_INVASIVENESS_3D_DN, REACTOME_MEMBRANE_TRAFFICKING, MORF_ESR1, MODULE_16, MORF_RAD51L3, GOBP_CELL_CELL_SIGNALING, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT

GO Biological Process (6): cell-cell signaling (GO:0007267), epidermis development (GO:0008544), trophoblast giant cell differentiation (GO:0060707), labyrinthine layer morphogenesis (GO:0060713), 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): connexin complex (GO:0005922), plasma membrane (GO:0005886), gap junction (GO:0005921), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Gap junction trafficking1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular process2
cell communication1
signaling1
tissue development1
cell differentiation involved in embryonic placenta development1
embryonic morphogenesis1
embryonic placenta morphogenesis1
labyrinthine layer development1
transport1
wide pore channel activity1
binding1
gap junction1
plasma membrane protein complex1
membrane1
cell periphery1
cell-cell junction1
cellular anatomical structure1
cell junction1

Protein interactions and networks

STRING

404 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
GJB5CACNA1CQ13936497
GJB5GJE1A6NN92458
GJB5VSIG1Q86XK7434
GJB5GOLT1AQ6ZVE7432
GJB5PKP1Q13835424
GJB5DSG3P32926416
GJB5FAT2Q9NYQ8387
GJB5PANX1Q96RD7353
GJB5JAKMIP2Q96AA8335
GJB5TP63Q9H3D4331
GJB5SERPINB13Q9UIV8310
GJB5CLCA2Q9UQC9310
GJB5CIMIP2CA6NJV1307
GJB5BHLHE22Q8NFJ8304
GJB5BTBD7Q9P203296

IntAct

121 interactions, top by confidence:

ABTypeScore
GJB5LPAR3psi-mi:“MI:0915”(physical association)0.560
GJB5MIPpsi-mi:“MI:0915”(physical association)0.560
GJB5FAM3Cpsi-mi:“MI:0915”(physical association)0.560
GJB5PLPP4psi-mi:“MI:0915”(physical association)0.560
SEC22BGJB5psi-mi:“MI:0915”(physical association)0.560
GJB5SERP1psi-mi:“MI:0915”(physical association)0.560
GJB5PGAP2psi-mi:“MI:0915”(physical association)0.560
GJB5NAPBpsi-mi:“MI:0915”(physical association)0.560
GJB5COMTpsi-mi:“MI:0915”(physical association)0.560
GJB5RPRMpsi-mi:“MI:0915”(physical association)0.560
GJB5AQP1psi-mi:“MI:0915”(physical association)0.560
GJB5VSTM1psi-mi:“MI:0915”(physical association)0.560
GJB5TMEM86Apsi-mi:“MI:0915”(physical association)0.560
GJB5TM4SF4psi-mi:“MI:0915”(physical association)0.560
GJB5SLC41A2psi-mi:“MI:0915”(physical association)0.560
GJB5CTXN3psi-mi:“MI:0915”(physical association)0.560
CYB5BGJB5psi-mi:“MI:0915”(physical association)0.560
GJB5TMEM128psi-mi:“MI:0915”(physical association)0.560
GJB5APOL2psi-mi:“MI:0915”(physical association)0.560
GJB5TMEM60psi-mi:“MI:0915”(physical association)0.560
GJB5TSPO2psi-mi:“MI:0915”(physical association)0.560
GJB5SLC38A7psi-mi:“MI:0915”(physical association)0.560
GJB5ARLNpsi-mi:“MI:0915”(physical association)0.560
GJB5SEC22Apsi-mi:“MI:0915”(physical association)0.560
GJB5psi-mi:“MI:0915”(physical association)0.560
GJB5ERG28psi-mi:“MI:0915”(physical association)0.560
GJB5PNLIPRP1psi-mi:“MI:0915”(physical association)0.560
GJB5TMEM97psi-mi:“MI:0915”(physical association)0.560
GJB5LRP10psi-mi:“MI:0915”(physical association)0.560
GJB5RTP2psi-mi:“MI:0915”(physical association)0.560

BioGRID (74): GJB5 (Affinity Capture-Western), CLTC (Affinity Capture-Western), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid), GJB5 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTI8, A6NN92, E9Q9H8, F6RWY9, O18968, O64761, O70610, O75712, O93533, O95377, O95452, P08033, P08034, P08983, P25305, P28230, P28231, P28232, P28233, P36380, P49111, P51916, P70689, P79826, Q02738, Q02739, Q0IIL2, Q13571, Q2KJA5, Q3SZ36, Q3T110, Q3TUD9, Q49LS6, Q4VV71, Q58D78, Q5E9Z5, Q5F410, Q5JW98, Q5REZ0, Q60HF7

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

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance38
Likely benign3
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

322 predictions. Top by Δscore:

VariantEffectΔscore
1:34755193:CAGG:Cdonor_loss1.0000
1:34755195:GGTAA:Gdonor_loss1.0000
1:34755196:G:GAdonor_loss1.0000
1:34757302:TGCA:Tacceptor_loss1.0000
1:34757303:GCA:Gacceptor_loss1.0000
1:34757305:A:AGacceptor_gain1.0000
1:34757305:AGTA:Aacceptor_loss1.0000
1:34757306:G:Aacceptor_loss1.0000
1:34757306:G:GAacceptor_gain1.0000
1:34757306:GT:Gacceptor_gain1.0000
1:34757306:GTA:Gacceptor_gain1.0000
1:34757306:GTAGC:Gacceptor_gain1.0000
1:34755196:G:GGdonor_gain0.9900
1:34755197:T:Adonor_loss0.9900
1:34756097:G:Tdonor_gain0.9800
1:34757302:T:TAacceptor_gain0.9800
1:34755191:CTCAG:Cdonor_gain0.9700
1:34757294:T:TAacceptor_gain0.9600
1:34757303:GCAGT:Gacceptor_gain0.9500
1:34757304:CAGTA:Cacceptor_gain0.9500
1:34757305:AGTAG:Aacceptor_gain0.9500
1:34755192:TCAG:Tdonor_gain0.9400
1:34755194:AG:Adonor_gain0.9400
1:34755195:GG:Gdonor_gain0.9400
1:34756097:G:GTdonor_gain0.9300
1:34757302:TGCAG:Tacceptor_gain0.9200
1:34757309:GC:Gacceptor_gain0.9200
1:34755193:CAG:Cdonor_gain0.9000
1:34757306:G:Tacceptor_gain0.9000
1:34757309:G:GAacceptor_gain0.9000

AlphaMissense

1795 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:34757730:A:CS134R0.984
1:34757732:C:AS134R0.984
1:34757732:C:GS134R0.984
1:34757744:G:CK138N0.979
1:34757744:G:TK138N0.979
1:34757856:T:CF176L0.979
1:34757858:C:AF176L0.979
1:34757858:C:GF176L0.979
1:34757482:T:GF51C0.977
1:34757586:T:CC86R0.977
1:34757487:T:AC53S0.974
1:34757488:G:CC53S0.974
1:34757879:G:CK183N0.974
1:34757879:G:TK183N0.974
1:34757853:T:AC175S0.973
1:34757854:G:CC175S0.973
1:34757855:C:GC175W0.973
1:34757462:G:CW44C0.972
1:34757462:G:TW44C0.972
1:34757508:T:AC60S0.971
1:34757509:G:CC60S0.971
1:34757400:T:AW24R0.969
1:34757400:T:CW24R0.969
1:34757481:T:CF51L0.969
1:34757483:C:AF51L0.969
1:34757483:C:GF51L0.969
1:34757763:T:CF145L0.969
1:34757765:T:AF145L0.969
1:34757765:T:GF145L0.969
1:34757835:T:AC169S0.968

dbSNP variants (sampled 300 via entrez): RS1000133756 (1:34753553 C>G), RS1000591147 (1:34756359 G>C), RS1000799738 (1:34756634 G>A), RS1001321641 (1:34753521 A>G), RS1001461932 (1:34758874 G>A), RS1001712898 (1:34756077 T>C), RS1002849825 (1:34755227 C>G,T), RS1003385380 (1:34754977 C>T), RS1004642573 (1:34756232 G>A), RS1006339921 (1:34758218 G>A), RS1007411350 (1:34754230 A>G), RS1007466840 (1:34754596 G>A), RS1008905308 (1:34755285 G>A), RS1009085015 (1:34755584 C>A,T), RS1009140060 (1:34755857 A>G)

Disease associations

OMIM: gene MIM:604493 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

StudyTraitp-value
GCST001523_14Visceral adipose tissue adjusted for BMI6.000000e-06
GCST005522_5Narcolepsy5.000000e-07
GCST007559_2Sleep duration (short sleep)5.000000e-08
GCST009612_3Triglyceride levels x thiazide or thiazide-like diuretics use interaction6.000000e-07
GCST012282_1BMI x environmental factors (excluding physical activity) interaction4.000000e-06
GCST012283_1BMI x environmental factors (including physical activity) interaction4.000000e-06

EFO canonical traits (9, from GWAS)

EFO IDTrait name
EFO:0004340body mass index
EFO:0004530triglyceride measurement
EFO:0006527smoking status measurement
EFO:0009374energy intake measurement
EFO:0009695household income
EFO:0010810protein intake measurement
EFO:0010811carbohydrate intake measurement
EFO:0011015educational attainment
EFO:0008002physical activity 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

13 total (human), top 13 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arseniteaffects splicing, decreases expression2
propionaldehydeincreases expression1
erucylphospho-N,N,N-trimethylpropylammoniumincreases expression1
Acetaminophenincreases expression1
Air Pollutantsdecreases expression, increases abundance1
Benzo(a)pyreneaffects methylation, decreases methylation1
Cisplatindecreases expression1
Dichlorodiphenyl Dichloroethylenedecreases expression1
Thiramdecreases expression1
Tobacco Smoke Pollutionincreases expression1
Valproic Acidincreases methylation1
Antirheumatic Agentsdecreases expression1
Particulate Matterdecreases expression, increases abundance1

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 76

This page pulls from 76 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot