MANSC1

Chr 12

MANSC domain containing 1

Also known as: 9130403P13Rik, LOH12CR3

The MANSC1 protein is predicted to function in the Golgi apparatus as a membrane-associated protein. Mutations cause autosomal recessive intellectual disability with macrocephaly, seizures, and hearing loss. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

Summary from RefSeq
Research Assistant →
0
Active trials
0
Pubs (1 yr)
42
P/LP submissions
0%
P/LP missense
1.33
LOEUF
DN
Mechanism· predicted
Clinical SummaryMANSC1
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 71 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.008
Z-score 1.00
OE 0.59 (0.291.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.28Z-score
OE missense 0.95 (0.851.06)
220 obs / 231.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.291.33)
00.351.4
Missense OE0.95 (0.851.06)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 4 / 6.8Missense obs/exp: 220 / 231.9Syn Z: -1.74
DN
0.6162th %ile
GOF
0.5856th %ile
LOF
0.2968th %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

127 submitted variants in ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic2
VUS71
Likely Benign9
Benign1
40
Pathogenic
2
Likely Pathogenic
71
VUS
9
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
40
0
40
Likely Pathogenic
0
0
2
0
2
VUS
0
63
8
0
71
Likely Benign
0
8
0
1
9
Benign
0
0
0
1
1
Total071502123

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

View in ClinVar →

Protein Context — Lollipop Plot

MANSC1 · 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
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found