GJB6
gap junction protein beta 6, the group of Gap junction proteins
Basic information
Region (hg38): 13:20221962-20232365
Previous symbols: [ "DFNA3", "ED2" ]
Links
Phenotypes
GenCC
Source:
- Clouston syndrome (Strong), mode of inheritance: AD
- Clouston syndrome (Moderate), mode of inheritance: AD
- autosomal dominant nonsyndromic hearing loss 3B (Limited), mode of inheritance: AD
- autosomal recessive nonsyndromic hearing loss 1B (Limited), mode of inheritance: AR
- KID syndrome (Supportive), mode of inheritance: AD
- Clouston syndrome (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 recessive nonsyndromic hearing loss 1B (Limited), mode of inheritance: AR
- Clouston syndrome (Definitive), mode of inheritance: AD
- autosomal recessive nonsyndromic hearing loss 1B (Limited), mode of inheritance: AR
- autosomal dominant nonsyndromic hearing loss 3B (Limited), mode of inheritance: AD
- Clouston syndrome (Strong), mode of inheritance: AD
- nonsyndromic genetic hearing loss (Refuted Evidence), mode of inheritance: AR
- Clouston syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Deafness, autosomal recessive 1B; Deafness, digenic | AR/Digenic | Audiologic/Otolaryngologic | Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dental; Dermatologic | 10471490; 11017065; 11807148; 11896458; 15150777; 15994881; 17041943; 18324688; 21465647 |
| Digenic inheritance (eg, with GJB2) has been described |
ClinVar
This is a list of variants' phenotypes submitted to
- Hidrotic_ectodermal_dysplasia_syndrome (99 variants)
- not_provided (80 variants)
- Autosomal_dominant_nonsyndromic_hearing_loss_3B (80 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_1A (79 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_1B (79 variants)
- Inborn_genetic_diseases (29 variants)
- not_specified (19 variants)
- GJB6-related_disorder (9 variants)
- X-linked_mixed_hearing_loss_with_perilymphatic_gusher (5 variants)
- Nonsyndromic_Deafness (2 variants)
- Hearing_impairment (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GJB6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001110219.3. 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 | 32 | 37 | ||||
| missense | 74 | 89 | ||||
| nonsense | 4 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 10 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 5 | 6 | 90 | 41 | 0 |
Highest pathogenic variant AF is 0.000578086
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GJB6 | protein_coding | protein_coding | ENST00000356192 | 1 | 10425 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.66e-7 | 0.132 | 125554 | 0 | 194 | 125748 | 0.000772 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.453 | 134 | 150 | 0.896 | 0.00000863 | 1737 |
| Missense in Polyphen | 47 | 62.111 | 0.75671 | 749 | ||
| Synonymous | -0.493 | 69 | 64.0 | 1.08 | 0.00000429 | 502 |
| Loss of Function | -0.211 | 10 | 9.31 | 1.07 | 6.67e-7 | 84 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000478 | 0.000478 |
| Ashkenazi Jewish | 0.0000994 | 0.0000992 |
| East Asian | 0.00158 | 0.00158 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.00114 | 0.00114 |
| Middle Eastern | 0.00158 | 0.00158 |
| South Asian | 0.000294 | 0.000294 |
| Other | 0.00179 | 0.00179 |
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: Ectodermal dysplasia 2, Clouston type (ECTD2) [MIM:129500]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD2 is an autosomal dominant condition characterized by atrichosis, nail hypoplasia and deformities, hyperpigmentation of the skin, normal teeth, normal sweat and sebaceous gland function. Palmoplantar hyperkeratosis is a frequent feature. Hearing impairment has been detected in few cases. {ECO:0000269|PubMed:11017065, ECO:0000269|PubMed:11874494}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 1B (DFNB1B) [MIM:612645]: 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:11807148, ECO:0000269|PubMed:15994881}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant, 3B (DFNA3B) [MIM:612643]: A form of non-syndromic sensorineural hearing loss characterized by a variable phenotype, ranging from bilateral middle to high frequency hearing loss to profound sensorineural deafness. 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:10471490}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Hair Follicle Development- Induction (Part 1 of 3);Calcium Regulation in the Cardiac Cell
(Consensus)
Recessive Scores
- pRec
- 0.322
Intolerance Scores
- loftool
- 0.0864
- rvis_EVS
- 0.26
- rvis_percentile_EVS
- 70.26
Haploinsufficiency Scores
- pHI
- 0.0532
- hipred
- N
- hipred_score
- 0.392
- ghis
- 0.442
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.450
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gjb6
- Phenotype
- homeostasis/metabolism phenotype; endocrine/exocrine gland 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); 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- cx30.3
- Affected structure
- sagitta
- Phenotype tag
- abnormal
- Phenotype quality
- decreased width
Gene ontology
- Biological process
- apoptotic process;cell communication;aging;sensory perception of sound;negative regulation of cell population proliferation;response to lipopolysaccharide;ear morphogenesis;inner ear development;response to electrical stimulus;cellular response to glucose stimulus
- Cellular component
- cytosol;connexin complex;integral component of membrane;apical plasma membrane;cell junction
- Molecular function