GJB4
protein-codinggap junction protein beta 4, the group of Gap junction proteins
Gene summary
This gene encodes a transmembrane connexin protein that is a component of gap junctions. Mutations in this gene have been associated with erythrokeratodermia variabilis, progressive symmetric erythrokeratoderma and hearing impairment. [provided by RefSeq, Dec 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0033012
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0033012
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0033012
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0033012
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0017851
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GJB4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153212.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 17 | 6 | 24 | ||
| missense | 4 | 4 | 79 | 10 | 4 | 101 |
| nonsense | 1 | 1 | 2 | 4 | ||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 4 | 5 | 84 | 30 | 10 | 133 |
Highest pathogenic variant AF is 0.00018090487
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_694944.1 | 1 | MANE Select | |
| Ensembl | ENSP00000345868.1 | 1 | MANE Select | |
| Ensembl | ENSP00000589412.1 | 1 | Standard | |
| Ensembl | ENSP00000808228.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Calcium Regulation in the Cardiac Cell
Biological Process
- cell communication
- sensory perception of smell
- olfactory behavior
Cellular Component
- nucleus
- nucleolus
- connexin complex
- integral component of membrane
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339480
- Coding exons
- 1
- Length
- 3984
- Individuals with no LoFs
- 116232
- Homozygous LoFs
- 200
- Heterozygous LoFs
- 9316
- Defined
- 125748
- p
- 0.0386
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.637 | 193 | 170 | 1.14 | 0.0000125 | 1720 |
| Missense (PolyPhen) | 79 | 64.648 | 1.222 | 722 | ||
| Synonymous | -1.57 | 94 | 76.5 | 1.23 | 0.00000583 | 558 |
| Loss of Function | 0.195 | 5 | 5.49 | 0.910 | 2.44e-7 | 67 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.096 | 0.064 | notable |
| Latino/Admixed American | 0.019 | 0.018 | notable |
| Ashkenazi Jewish | 0.018 | 0.018 | notable |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.055 | 0.056 | notable |
| European (Non-Finnish) | 0.049 | 0.049 | notable |
| South Asian | 0.032 | 0.031 | notable |
| Other | 0.038 | 0.036 | notable |
dbNSFP Gene Annotations
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: Erythrokeratodermia variabilis et progressiva 2 (EKVP2) [MIM:617524]: A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. {ECO:0000269|PubMed:11017804, ECO:0000269|PubMed:12648223, ECO:0000269|PubMed:19291775}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.141
- RVIS EVS
- 0.64
- RVIS percentile EVS
- 84.1
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.224
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |