ASCC3

Chr 6AR

activating signal cointegrator 1 complex subunit 3

Also known as: ASC1p200, HELIC1, MRT81, RNAH

This gene encodes an ATPase and 3'-5' DNA helicase that functions in DNA repair of alkylated DNA and in the ribosome quality control pathway that rescues stalled ribosomes during problematic translation. Mutations cause spastic tetraplegia 20, an autosomal recessive disorder characterized by early-onset spastic quadriplegia and intellectual disability. The gene is highly constrained against loss-of-function variants, indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismARLOEUF 0.571 OMIM phenotype
Clinical SummaryASCC3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 291 VUS of 425 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 5.58
OE 0.45 (0.360.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.23Z-score
OE missense 0.82 (0.770.86)
938 obs / 1150.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.45 (0.360.57)
00.351.4
Missense OE0.82 (0.770.86)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 55 / 121.3Missense obs/exp: 938 / 1150.8Syn Z: -0.37
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedASCC3-related intellectual developmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6743th %ile
GOF
0.5465th %ile
LOF
0.3454th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

425 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS291
Likely Benign28
Benign9
Conflicting3
27
Pathogenic
4
Likely Pathogenic
291
VUS
28
Likely Benign
9
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
5
18
0
27
Likely Pathogenic
4
0
0
0
4
VUS
12
262
16
1
291
Likely Benign
0
9
1
18
28
Benign
0
3
2
4
9
Conflicting
3
Total202793723362

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

View in ClinVar →

Protein Context — Lollipop Plot

ASCC3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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