MANSC1

Chr 12

MANSC domain containing 1

Also known as: 9130403P13Rik, LOH12CR3

NCBI Gene: 54682 ENSG00000111261 UniProt: Q9H8J5

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.

ResearchSummary from RefSeq

Predicted to be located in membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.008

Z-score 1.00

OE 0.59 (0.29–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.28Z-score

OE missense 0.95 (0.85–1.06)

220 obs / 231.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.29–1.33)

0≤0.351.4

Missense OE?0.95 (0.85–1.06)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 4 / 6.8Missense obs/exp: 220 / 231.9Syn Z: -1.74

Background carrier burden — how many people carry a rare variant somewhere in MANSC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

522 rare PASS variants

Rare truncating (LoF)

1 in 460

81 rare PASS variants

Rare synonymous (reference)

1 in 160

239 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MANSC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 400
South Asian	~43k	1 in 77	1 in 600
Remaining (unassigned)	~30k	1 in 68	1 in 550
European (Finnish)	~27k	1 in 480	1 in 1,000
Admixed American	~22k	1 in 100	≈ 1 in 4,500
African / African American	~21k	1 in 79	1 in 1,300
East Asian	~20k	1 in 120	1 in 1,000
Ashkenazi Jewish	~13k	1 in 360	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 88	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓