MAN2C1

Chr 15AR

mannosidase alpha class 2C member 1

Also known as: CDDG2, MAN6A8, MANA, MANA1

NCBI Gene: 4123ENSG00000140400UniProt: Q9NTJ4

Predicted to enable alpha-mannosidase activity. Predicted to be involved in oligosaccharide catabolic process. Located in nucleoplasm. Implicated in congenital disorder of deglycosylation 2. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Congenital disorder of deglycosylation 2MIM #619775
AR
282
ClinVar variants
40
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MAN2C1
🧬
Gene-Disease Validity (ClinGen)
congenital disorder of deglycosylation 2 · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 229 VUS of 282 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.08LOEUF
pLI 0.000
Z-score 1.06
OE 0.85 (0.68–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.16Z-score
OE missense 0.98 (0.92–1.05)
627 obs / 638.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.85 (0.68–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.92–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 49 / 57.7Missense obs/exp: 627 / 638.0Syn Z: 0.18

ClinVar Variant Classifications

282 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic12
VUS229
Likely Benign10
Benign1
Conflicting2
28
Pathogenic
12
Likely Pathogenic
229
VUS
10
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
6
2
4
0
12
VUS
2
213
14
0
229
Likely Benign
0
7
0
3
10
Benign
0
0
1
0
1
Conflicting
—2
Total8222473282

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

View in ClinVar →

Protein Context — Lollipop Plot

MAN2C1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MAN2C1-related neurodevelopmental disorder with cerebral malformations

strong
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of deglycosylation 2

MIM #619775

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools