MAN1C1

Chr 1

mannosidase alpha class 1C member 1

Also known as: HMIC, MAN1A3, MAN1C, pp6318

NCBI Gene: 57134ENSG00000117643UniProt: Q9NR34OMIM: 616772

The protein trims alpha-1,2-linked mannose residues from N-linked oligosaccharides during glycoprotein maturation, converting Man(9)GlcNAc(2) to smaller mannose structures. Mutations cause autosomal recessive intellectual disability with characteristic dysmorphic features including coarse facies, often with onset in early childhood. This gene is highly constrained against loss-of-function variants, reflecting its essential role in cellular glycosylation processes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.43
Clinical Summary— MAN1C1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 92 VUS of 122 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.209
Z-score 4.06
OE 0.24 (0.14–0.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.66Z-score
OE missense 0.76 (0.69–0.83)
278 obs / 367.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.14–0.43)
0≤0.351.4
Missense OE0.76 (0.69–0.83)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 8 / 33.3Missense obs/exp: 278 / 367.7Syn Z: -0.76
DN
0.6550th %ile
GOF
0.5660th %ile
LOF
0.3258th %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

ClinVar

Classification Summary

Pathogenic6
VUS92
Likely Benign10
Benign3
6
Pathogenic
92
VUS
10
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
84
8
0
92
Likely Benign
0
0
3
7
10
Benign
0
1
1
1
3
Total085188111

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

View in ClinVar →

Protein Context — Lollipop Plot

MAN1C1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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