ASCC3

Chr 6AR

activating signal cointegrator 1 complex subunit 3

Also known as: ASC1p200, HELIC1, MRT81, RNAH

NCBI Gene: 10973ENSG00000112249UniProt: Q8N3C0

This gene encodes a protein that belongs to a family of helicases that are involved in the ATP-dependent unwinding of nucleic acid duplexes. The encoded protein is the largest subunit of the activating signal cointegrator 1 complex that is involved in DNA repair and resistance to alkylation damage. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 81MIM #620700
AR
0
Active trials
19
Pathogenic / LP
252
ClinVar variants
6
Pubs (1 yr)
2.2
Missense Z
0.57
LOEUF
Clinical Summary— ASCC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 203 VUS of 252 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 5.58
OE 0.45 (0.36–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.23Z-score
OE missense 0.82 (0.77–0.86)
938 obs / 1150.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.45 (0.36–0.57)
0≤0.351.4
Missense OE0.82 (0.77–0.86)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 55 / 121.3Missense obs/exp: 938 / 1150.8Syn Z: -0.37
DN
DN
0.6743th %ile
GOF
0.5465th %ile
LOF
0.3454th %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

252 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS203
Likely Benign19
Benign10
Conflicting1
17
Pathogenic
2
Likely Pathogenic
203
VUS
19
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
2
0
0
0
2
VUS
6
183
13
1
203
Likely Benign
0
9
1
9
19
Benign
0
3
2
5
10
Conflicting
—1
Total81953315252

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

View in ClinVar →

ASCC3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ASCC3-related intellectual developmental disorder

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients