ASIC3
protein-codingacid sensing ion channel subunit 3, the group of Acid sensing ion channel subunits
Gene summary
This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, two hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene is an acid sensor and may play an important role in the detection of lasting pH changes. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 2 has been observed as proton-gated channels sensitive to gadolinium. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]
- ACCN3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.5 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 ASIC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004769.4. 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 | 1 | 3 | 4 | |||
| missense | 101 | 8 | 2 | 111 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 107 | 11 | 2 | 120 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004760.1 | 11 | MANE Select | |
| Ensembl | ENSP00000344838.5 | 11 | MANE Select | |
| RefSeq | NP_064717.1 | 11 | Standard | |
| RefSeq | NP_064718.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
Biological Process
- signal transduction
- sensory perception
- response to heat
- response to acidic pH
- ion transmembrane transport
Molecular Function
- cation channel activity
- sodium channel activity
- enterobactin transmembrane transporter activity
- acid-sensing ion channel activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297512
- Coding exons
- 11
- Length
- 4465
- Individuals with no LoFs
- 125345
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 400
- Defined
- 125745
- p
- 0.00159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.631 | 387 | 354 | 1.09 | 0.0000221 | 3524 |
| Missense (PolyPhen) | 148 | 138.67 | 1.0673 | 1382 | ||
| Synonymous | -1.07 | 165 | 148 | 1.11 | 0.00000982 | 1144 |
| Loss of Function | 2.26 | 15 | 27.9 | 0.537 | 0.00000167 | 265 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0010 | notable |
| Latino/Admixed American | 0.00058 | 0.00058 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.0014 | 0.0014 | notable |
| Finnish | 0.00079 | 0.00079 | rare |
| European (Non-Finnish) | 0.0024 | 0.0024 | notable |
| South Asian | 0.0012 | 0.0012 | notable |
| Other | 0.00081 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties. {ECO:0000269|PubMed:9744806, ECO:0000269|PubMed:9886053}.;
Intolerance Scores
- RVIS EVS
- 0.25
- RVIS percentile EVS
- 69.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |