GJB2
gap junction protein beta 2, the group of Gap junction proteins
Basic information
Region (hg38): 13:20187463-20192938
Previous symbols: [ "DFNB1", "DFNA3" ]
Links
Phenotypes
GenCC
Source:
- autosomal recessive nonsyndromic hearing loss 1A (Strong), mode of inheritance: AR
- ichthyosis, hystrix-like, with hearing loss (Strong), mode of inheritance: AD
- palmoplantar keratoderma-deafness syndrome (Strong), mode of inheritance: AD
- autosomal dominant keratitis-ichthyosis-hearing loss syndrome (Strong), mode of inheritance: AD
- keratoderma hereditarium mutilans (Strong), mode of inheritance: AD
- Bart-Pumphrey syndrome (Strong), mode of inheritance: AD
- autosomal recessive nonsyndromic hearing loss 1A (Definitive), mode of inheritance: AR
- KID syndrome (Supportive), mode of inheritance: AD
- palmoplantar keratoderma-deafness syndrome (Supportive), mode of inheritance: AD
- keratoderma hereditarium mutilans (Supportive), mode of inheritance: AD
- autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
- hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
- autosomal dominant keratitis-ichthyosis-hearing loss syndrome (Moderate), mode of inheritance: AD
- autosomal dominant nonsyndromic hearing loss 3A (Strong), mode of inheritance: AD
- autosomal recessive nonsyndromic hearing loss 1A (Definitive), mode of inheritance: AR
- ichthyosis, hystrix-like, with hearing loss (Definitive), mode of inheritance: AD
- Bart-Pumphrey syndrome (Definitive), mode of inheritance: AD
- palmoplantar keratoderma-deafness syndrome (Definitive), mode of inheritance: AD
- keratoderma hereditarium mutilans (Definitive), mode of inheritance: AD
- autosomal recessive nonsyndromic hearing loss 1A (Strong), mode of inheritance: AR
- autosomal dominant nonsyndromic hearing loss 3A (Strong), mode of inheritance: AD
- Bart-Pumphrey syndrome (Strong), mode of inheritance: AD
- hearing loss, autosomal recessive (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Deafness, autosomal dominant 3A; Keratitis-icthyosis-deafness syndrome, autosomal dominant; Deafness, autosomal recessive 1A; Deafness, digenic; Hystrix-like ichthyosis with deafness; Bart-Pumphrey syndrome; Keratoderma, palmoplantar, with deafness; Vohwinkel syndrome | AD/AR/Digenic | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Oncologic | Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In certain conditions (eg, KID syndrome), infectious and malignant complications may benefit from surveillance leading to microbial prophylaxis and early and aggressive treatment of infections and early detection and treatment of malignancy | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Oncologic; Ophthalmologic | 6015974; 1532426; 8010352; 7748756; 9139825; 9529365; 9620796; 10218527; 10369869; 10633135; 10807696; 11298683; 11807148; 12047643; 11960582; 11912510; 11889383; 12372058; 12072059; 11918723; 12560944; 14694360; 15150777; 15482471; 14700667; 16222667; 16380907; 15994881; 15633193; 15691545; 15996214; 16840571; 17041943; 17330861; 993581; 17041943; 19050930; 18843290; 20815033; 20412116 |
| In nonsyndromic deafness, onset of AD disease can be pre or postlingual; In syndromic disease, although skin and other findings may be obvious in some individuals, the syndromic combination of features may not be as readily appreciated as being related to hearing impairment; Digenic inheritance (with GJB3, GJB6) has been described |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (412 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_1A (260 variants)
- Autosomal_dominant_nonsyndromic_hearing_loss_3A (145 variants)
- not_specified (123 variants)
- Ichthyosis,_hystrix-like,_with_hearing_loss (119 variants)
- Autosomal_dominant_keratitis-ichthyosis-hearing_loss_syndrome (107 variants)
- Palmoplantar_keratoderma-deafness_syndrome (107 variants)
- Mutilating_keratoderma (104 variants)
- Knuckle_pads,_deafness_AND_leukonychia_syndrome (103 variants)
- Nonsyndromic_genetic_hearing_loss (89 variants)
- Rare_genetic_deafness (63 variants)
- GJB2-related_disorder (41 variants)
- X-linked_mixed_hearing_loss_with_perilymphatic_gusher (40 variants)
- Hearing_loss (37 variants)
- Hearing_impairment (31 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_1B (16 variants)
- Inborn_genetic_diseases (13 variants)
- Hearing_loss,_autosomal_recessive (9 variants)
- Nonsyndromic_Deafness (7 variants)
- Monogenic_hearing_loss (7 variants)
- Hereditary_palmoplantar_keratoderma (5 variants)
- nonsyndromic_sensorineural_hearing_loss (5 variants)
- Sensorineural_hearing_loss_disorder (5 variants)
- Intellectual_disability (3 variants)
- Ear_malformation (3 variants)
- Deafness (3 variants)
- See_cases (3 variants)
- Progressive_sensorineural_hearing_impairment (2 variants)
- Autism_spectrum_disorder (2 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_104 (2 variants)
- IFAP_syndrome_1,_with_or_without_BRESHECK_syndrome (1 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_12 (1 variants)
- CREBBP-related_disorder (1 variants)
- Bilateral_sensorineural_hearing_impairment (1 variants)
- Noonan_syndrome_1 (1 variants)
- Severe_sensorineural_hearing_impairment (1 variants)
- Bilateral_conductive_hearing_impairment (1 variants)
- Porokeratotic_adnexal_ostial_nevus (1 variants)
- Ichthyosis_and_erythrokeratoderma (1 variants)
- Deafness,_digenic,_GJB2/GJB6 (1 variants)
- Deafness,_digenic,_GJB2/GJB3 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GJB2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004004.6. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 118 | 122 | ||||
| missense | 54 | 108 | 119 | 15 | 299 | |
| nonsense | 20 | 13 | 34 | |||
| start loss | 4 | 1 | 5 | |||
| frameshift | 41 | 27 | 69 | |||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| Total | 119 | 153 | 126 | 133 | 4 |
Highest pathogenic variant AF is 0.012041303
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GJB2 | protein_coding | protein_coding | ENST00000382844 | 1 | 5429 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 6.56e-16 | 0.000154 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.720 | 161 | 137 | 1.17 | 0.00000846 | 1481 |
| Missense in Polyphen | 70 | 67.124 | 1.0428 | 721 | ||
| Synonymous | -0.293 | 64 | 61.1 | 1.05 | 0.00000437 | 446 |
| Loss of Function | -3.82 | 17 | 6.50 | 2.62 | 2.82e-7 | 69 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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: 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. {ECO:0000269|PubMed:10830906, ECO:0000269|PubMed:11313763, ECO:0000269|PubMed:11439000, ECO:0000269|PubMed:12121355, ECO:0000269|PubMed:12239718, ECO:0000269|PubMed:12786758, ECO:0000269|PubMed:14722929, ECO:0000269|PubMed:15592461, ECO:0000269|PubMed:15666300, ECO:0000269|PubMed:15994881, ECO:0000269|PubMed:17660464, ECO:0000269|PubMed:17666888, ECO:0000269|PubMed:19384972, ECO:0000269|PubMed:23680645, ECO:0000269|PubMed:28281779, ECO:0000269|PubMed:9328482, ECO:0000269|PubMed:9336442, ECO:0000269|PubMed:9471561, ECO:0000269|PubMed:9529365}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10807696, ECO:0000269|PubMed:11313763, ECO:0000269|PubMed:11439000, ECO:0000269|PubMed:12668604, ECO:0000269|PubMed:12786758, ECO:0000269|PubMed:19384972, ECO:0000269|PubMed:9620796}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Vohwinkel syndrome (VOWNKL) [MIM:124500]: An autosomal dominant disease characterized by hyperkeratosis, constriction on fingers and toes and congenital deafness. {ECO:0000269|PubMed:10369869, ECO:0000269|PubMed:12668604, ECO:0000269|PubMed:15954104, ECO:0000269|PubMed:18688874}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10633135, ECO:0000269|PubMed:10757647, ECO:0000269|PubMed:12372058, ECO:0000269|PubMed:12668604, ECO:0000269|PubMed:15996214, ECO:0000269|PubMed:17993581, ECO:0000269|PubMed:9856479}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratitis-ichthyosis-deafness syndrome (KID syndrome) [MIM:148210]: An autosomal dominant form of ectodermal dysplasia. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Keratitis-ichthyosis-deafness syndrome is 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. {ECO:0000269|PubMed:11912510, ECO:0000269|PubMed:12548749, ECO:0000269|PubMed:12752120}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bart-Pumphrey syndrome (BPS) [MIM:149200]: An autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability. {ECO:0000269|PubMed:15482471, ECO:0000269|PubMed:15952212}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:12072059}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Calcium Regulation in the Cardiac Cell;Vesicle-mediated transport;Membrane Trafficking;Transport of connexins along the secretory pathway;Oligomerization of connexins into connexons;Transport of connexons to the plasma membrane;Gap junction assembly;Gap junction trafficking;Gap junction trafficking and regulation
(Consensus)
Recessive Scores
- pRec
- 0.506
Intolerance Scores
- loftool
- 0.163
- rvis_EVS
- 0.66
- rvis_percentile_EVS
- 84.55
Haploinsufficiency Scores
- pHI
- 0.429
- hipred
- N
- hipred_score
- 0.473
- ghis
- 0.429
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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gjb2
- Phenotype
- cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; normal 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); embryo phenotype; skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear 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); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype;
Zebrafish Information Network
- Gene name
- cx30.3
- Affected structure
- sagitta
- Phenotype tag
- abnormal
- Phenotype quality
- decreased width
Gene ontology
- Biological process
- response to ischemia;cell-cell signaling;aging;sensory perception of sound;gap junction assembly;response to estradiol;response to lipopolysaccharide;response to retinoic acid;response to progesterone;cellular response to oxidative stress;response to human chorionic gonadotropin;response to antibiotic;decidualization;inner ear development;transmembrane transport;cellular response to glucagon stimulus;cellular response to dexamethasone stimulus;epididymis development
- Cellular component
- endoplasmic reticulum-Golgi intermediate compartment;cytosol;plasma membrane;connexin complex;integral component of membrane;lateral plasma membrane;cell body;perinuclear region of cytoplasm;astrocyte projection
- Molecular function
- gap junction channel activity;identical protein binding