CACNG4
protein-codingcalcium voltage-gated channel auxiliary subunit gamma 4, the group of Calcium channel auxiliary gamma subunits
Gene summary
The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members, a type II TARP and a calcium channel gamma subunit. [provided by RefSeq, Dec 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~68.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CACNG4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014405.4. 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 | 0 | |||||
| missense | 42 | 42 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 43 | 0 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055220.1 | 4 | MANE Select | |
| Ensembl | ENSP00000262138.3 | 4 | MANE Select | |
| Ensembl | ENSP00000591524.1 | 3 | Standard | |
| Ensembl | ENSP00000591524.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Oxytocin signaling pathway - Homo sapiens (human)
- Cardiac muscle contraction - Homo sapiens (human)
- Dilated cardiomyopathy (DCM) - Homo sapiens (human)
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)
- Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
Biological Process
- transmission of nerve impulse
- response to cocaine
- membrane depolarization
- positive regulation of synaptic transmission, glutamatergic
- calcium ion transmembrane transport
Molecular Function
- voltage-gated calcium channel activity
- calcium channel regulator activity
- calcium channel activity
- channel regulator activity
- ionotropic glutamate receptor binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell surface
- endocytic vesicle membrane
- AMPA glutamate receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262138
- Coding exons
- 4
- Length
- 68489
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.82 | 138 | 213 | 0.648 | 0.0000134 | 2132 |
| Missense (PolyPhen) | 47 | 76.722 | 0.6126 | 780 | ||
| Synonymous | -0.108 | 95 | 93.7 | 1.01 | 0.00000621 | 673 |
| Loss of Function | 2.01 | 5 | 12.7 | 0.392 | 7.99e-7 | 121 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000058 | 0.000046 | rare |
| European (Non-Finnish) | 0.000029 | 0.000026 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (PubMed:21127204). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs), including GRIA1 and GRIA4. Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization (PubMed:21172611). {ECO:0000269|PubMed:21127204, ECO:0000269|PubMed:21172611}.;
Recessive Scores
- pRec
- 0.117
Intolerance Scores
- LoFtool
- 0.198
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.345
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |