ASIC5

Chr 4

acid sensing ion channel subunit family member 5

Also known as: ACCN5, BASIC, HINAC, INAC

The protein forms bile acid-gated sodium channels that control sodium transport in intestinal and bile duct epithelial cells, and may regulate electrical activity in cerebellar cells involved in motor coordination and balance. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. This gene shows very low constraint against loss-of-function mutations, consistent with autosomal recessive inheritance where heterozygous carriers are typically unaffected.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
30
P/LP submissions
3%
P/LP missense
1.37
LOEUF
DN
Mechanism· predicted
Clinical SummaryASIC5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 77 VUS of 122 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.37LOEUF
pLI 0.000
Z-score 0.22
OE 0.95 (0.671.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.33Z-score
OE missense 1.06 (0.961.17)
273 obs / 258.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.95 (0.671.37)
00.351.4
Missense OE1.06 (0.961.17)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 21 / 22.1Missense obs/exp: 273 / 258.2Syn Z: -0.99
DN
0.6454th %ile
GOF
0.6249th %ile
LOF
0.2583th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

122 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS77
Likely Benign11
27
Pathogenic
3
Likely Pathogenic
77
VUS
11
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
26
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
69
8
0
77
Likely Benign
0
10
1
0
11
Benign
0
0
0
0
0
Total080380118

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ASIC5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding the Genetic Landscape of Usher-Like Phenotypes.
Fuster-García C et al.·Invest Ophthalmol Vis Sci
2019
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC