GeneBe

GJB1

gap junction protein beta 1, the group of Gap junction proteins

Basic information

Region (hg38): X:71212811-71225516

Previous symbols: [ "CMTX1", "CMTX" ]

Links

ENSG00000169562 ∙ NCBI:2705 ∙ OMIM:304040 ∙ HGNC:4283 ∙ Uniprot:P08034 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Charcot-Marie-Tooth disease X-linked dominant 1 (Moderate), mode of inheritance: XL
  • Charcot-Marie-Tooth disease X-linked dominant 1 (Strong), mode of inheritance: XL
  • X-linked progressive cerebellar ataxia (Supportive), mode of inheritance: XL
  • Charcot-Marie-Tooth disease X-linked dominant 1 (Supportive), mode of inheritance: XL
  • Charcot-Marie-Tooth disease X-linked dominant 1 (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Charcot-Marie-Tooth neuropathy, X-linked dominant, 1XLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic8266101; 10487913; 17100997; 17353473; 21254193; 21504505; 21692908; 21922480; 21692908; 22483671; 22577229

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GJB1 gene.

  • Charcot-Marie-Tooth_Neuropathy_X (476 variants)
  • Charcot-Marie-Tooth_disease (381 variants)
  • Charcot-Marie-Tooth_disease_X-linked_dominant_1 (221 variants)
  • not_provided (164 variants)
  • Inborn_genetic_diseases (53 variants)
  • not_specified (39 variants)
  • GJB1-related_disorder (10 variants)
  • Peripheral_neuropathy (5 variants)
  • Dejerine-Sottas_disease (3 variants)
  • Hand_muscle_atrophy (2 variants)
  • Hammertoe (2 variants)
  • Talipes_cavus_equinovarus (1 variants)
  • Distal_muscle_weakness (1 variants)
  • Reduced_tendon_reflexes (1 variants)
  • Decreased_nerve_conduction_velocity (1 variants)
  • Peroneal_muscle_atrophy (1 variants)
  • Distal_lower_limb_muscle_weakness (1 variants)
  • Pain (1 variants)
  • Pes_cavus (1 variants)
  • Charcot-Marie-Tooth_disease-hearing_loss-intellectual_disability_syndrome (1 variants)
  • Progressive_distal_muscular_atrophy (1 variants)
  • Cerebellar_ataxia (1 variants)
  • Sensory_neuropathy (1 variants)
  • Distal_sensory_impairment (1 variants)
  • Achilles_tendon_contracture (1 variants)
  • Progressive_distal_muscle_weakness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GJB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000166.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
3
clinvar
101
clinvar
5
clinvar
 111
missense
56
clinvar
128
clinvar
326
clinvar
10
clinvar
1
clinvar
 521
nonsense
22
clinvar
6
clinvar
9
clinvar
 37
start loss
4
1
3
 8
frameshift
39
clinvar
15
clinvar
35
clinvar
 89
splice donor/acceptor (+/-2bp)
2
clinvar
2
clinvar
 4
Total 123 152 378 111 6

Highest pathogenic variant AF is 0.00000901892

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
GJB1protein_codingprotein_codingENST00000374022 110323
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.8460.15100000.00
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.03661310.5020.00001171828
Missense in Polyphen1054.8090.18245839
Synonymous0.4134952.80.9280.00000445604
Loss of Function2.3006.150.005.38e-782

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
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.;
Disease
DISEASE: Charcot-Marie-Tooth disease, X-linked dominant, 1 (CMTX1) [MIM:302800]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. CMTX1 has both demyelinating and axonal features. Central nervous system involvement may occur. {ECO:0000269|PubMed:10071100, ECO:0000269|PubMed:10220155, ECO:0000269|PubMed:10234007, ECO:0000269|PubMed:10586284, ECO:0000269|PubMed:10732813, ECO:0000269|PubMed:10737979, ECO:0000269|PubMed:10873293, ECO:0000269|PubMed:10894999, ECO:0000269|PubMed:10923043, ECO:0000269|PubMed:10938190, ECO:0000269|PubMed:11030070, ECO:0000269|PubMed:11140841, ECO:0000269|PubMed:11180613, ECO:0000269|PubMed:11437164, ECO:0000269|PubMed:11438991, ECO:0000269|PubMed:11562788, ECO:0000269|PubMed:11571214, ECO:0000269|PubMed:11723288, ECO:0000269|PubMed:11835375, ECO:0000269|PubMed:11891346, ECO:0000269|PubMed:12185164, ECO:0000269|PubMed:12207932, ECO:0000269|PubMed:12325071, ECO:0000269|PubMed:12402337, ECO:0000269|PubMed:12477701, ECO:0000269|PubMed:12497641, ECO:0000269|PubMed:12536289, ECO:0000269|PubMed:12707076, ECO:0000269|PubMed:14627639, ECO:0000269|PubMed:15241803, ECO:0000269|PubMed:15468313, ECO:0000269|PubMed:15852376, ECO:0000269|PubMed:27234031, ECO:0000269|PubMed:7477983, ECO:0000269|PubMed:7833935, ECO:0000269|PubMed:8004109, ECO:0000269|PubMed:8162049, ECO:0000269|PubMed:8266101, ECO:0000269|PubMed:8628473, ECO:0000269|PubMed:8698335, ECO:0000269|PubMed:8733054, ECO:0000269|PubMed:8737658, ECO:0000269|PubMed:8807343, ECO:0000269|PubMed:8829637, ECO:0000269|PubMed:8889588, ECO:0000269|PubMed:8956046, ECO:0000269|PubMed:8990008, ECO:0000269|PubMed:9018031, ECO:0000269|PubMed:9099841, ECO:0000269|PubMed:9187667, ECO:0000269|PubMed:9272161, ECO:0000269|PubMed:9361298, ECO:0000269|PubMed:9452025, ECO:0000269|PubMed:9452099, ECO:0000269|PubMed:9469569, ECO:0000269|PubMed:9633821, ECO:0000269|PubMed:9818870, ECO:0000269|PubMed:9856562, ECO:0000269|Ref.12}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dejerine-Sottas syndrome (DSS) [MIM:145900]: A severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. Characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome. {ECO:0000269|PubMed:15947997}. Note=The gene represented in this entry may act as a disease modifier.;
Pathway
Neural Crest Differentiation;Common Pathways Underlying Drug Addiction;Calcium Regulation in the Cardiac Cell;Vesicle-mediated transport;Membrane Trafficking;Transport of connexins along the secretory pathway;Oligomerization of connexins into connexons;Gap junction assembly;Gap junction trafficking;Gap junction trafficking and regulation (Consensus)

Recessive Scores

pRec
0.440

Intolerance Scores

loftool
rvis_EVS
0.21
rvis_percentile_EVS
67.72

Haploinsufficiency Scores

pHI
0.824
hipred
Y
hipred_score
0.642
ghis
0.409

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.801

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Gjb1
Phenotype
homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process
cell-cell signaling;nervous system development;purine ribonucleotide transport;gap junction assembly;protein complex oligomerization;transmembrane transport;epididymis development
Cellular component
endoplasmic reticulum membrane;connexin complex;integral component of membrane;lateral plasma membrane
Molecular function
gap junction channel activity;protein homodimerization activity