CACNG1
protein-codingcalcium voltage-gated channel auxiliary subunit gamma 1, the group of Calcium channel auxiliary gamma subunits
Gene summary
Voltage-dependent calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is part of skeletal muscle 1,4-dihydropyridine-sensitive calcium channels and is an integral membrane protein that plays a role in excitation-contraction coupling. 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 that function as transmembrane AMPA receptor regulatory proteins (TARPs). [provided by RefSeq, Dec 2010]
- CACNLG
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.2 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 CACNG1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000727.4. 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 | 2 | 2 | ||||
| missense | 40 | 2 | 42 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 2 | 0 | 44 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000718.1 | 4 | MANE Select | |
| Ensembl | ENSP00000226021.3 | 4 | MANE Select | |
| Ensembl | ENSP00000628746.1 | 5 | Standard | |
| Ensembl | ENSP00000628746.1 | 5 | 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
- sarcoplasmic reticulum calcium ion transport
- calcium ion transmembrane transport
- regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
Molecular Function
- voltage-gated calcium channel activity
- calcium channel regulator activity
- protein binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- T-tubule
- sarcolemma
- L-type voltage-gated calcium channel complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000226021
- Coding exons
- 4
- Length
- 12204
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125747
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.321 | 141 | 152 | 0.927 | 0.0000101 | 1453 |
| Missense (PolyPhen) | 38 | 48.146 | 0.78926 | 459 | ||
| Synonymous | -0.225 | 71 | 68.6 | 1.03 | 0.00000537 | 442 |
| Loss of Function | -0.539 | 11 | 9.23 | 1.19 | 4.78e-7 | 94 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics. {ECO:0000250|UniProtKB:P19518}.;
Recessive Scores
- pRec
- 0.0998
Intolerance Scores
- LoFtool
- 0.707
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.171
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |