MAN2A1

Chr 5

mannosidase alpha class 2A member 1

Also known as: AMan II, GOLIM7, MANA2, MANII

NCBI Gene: 4124ENSG00000112893UniProt: Q16706

This gene encodes a glycosyl hydrolase that localizes to the Golgi and catalyzes the final hydrolytic step in the asparagine-linked oligosaccharide (N-glycan) maturation pathway. Mutations in the mouse homolog of this gene have been shown to cause a systemic autoimmune disease similar to human systemic lupus erythematosus. [provided by RefSeq, Dec 2013]

199
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MAN2A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 162 VUS of 199 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.
0.62LOEUF
pLI 0.000
Z-score 3.98
OE 0.45 (0.33–0.62)
Tolerant

Typical tolerance to LoF variation

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.
0.43Z-score
OE missense 0.95 (0.89–1.02)
560 obs / 589.2 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.0.45 (0.33–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.89–1.02)
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.1.25
0≤1.21.6
LoF obs/exp: 27 / 60.3Missense obs/exp: 560 / 589.2Syn Z: -2.80

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS162
Likely Benign12
Benign1
23
Pathogenic
1
Likely Pathogenic
162
VUS
12
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
1
0
1
VUS
0
152
10
0
162
Likely Benign
0
10
1
1
12
Benign
0
0
1
0
1
Total0162361199

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

View in ClinVar →

Protein Context — Lollipop Plot

MAN2A1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Homozygous truncating variant in MAN2A2 causes a novel congenital disorder of glycosylation with neurological involvement.
Mahajan S et al.·J Med Genet
2023
Glycobiology and schizophrenia: a biological hypothesis emerging from genomic research.
Mealer RG et al.·Mol Psychiatry
2020Review
Inhibition of MAN2A1 Enhances the Immune Response to Anti-PD-L1 in Human Tumors.
Shi S et al.·Clin Cancer Res
2020
Whole-exome sequencing reveals novel genomic signatures and potential therapeutic targets during the progression of rectal neuroendocrine neoplasm.
Xu S et al.·Cell Death Dis
2024
Imputed expression of schizophrenia-associated genes and cognitive measures in patients with schizophrenia.
Fabbri C et al.·Mol Genet Genomic Med
2022Cohort
Novel fusion transcripts associate with progressive prostate cancer.
Yu YP et al.·Am J Pathol
2014
Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation.
Yan W et al.·Int J Mol Med
2018
Plasma Protein Biomarkers to Detect Early Gastric Preneoplasia and Cancer: A Prospective Study.
Giai Gianetto Q et al.·Int J Mol Sci
2025
MAN2A2-related glycosylation defects in autism and cognitive delay.
Treccarichi S et al.·Sci Rep
2025Case report
Association of chromosome 5q21.3 polymorphisms with the exploratory eye movement dysfunction in schizophrenia.
Ma Y et al.·Sci Rep
2015
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