MAN1A1

Chr 6

mannosidase alpha class 1A member 1

Also known as: HUMM3, HUMM9, MAN9

NCBI Gene: 4121ENSG00000111885UniProt: P33908

This gene encodes a class I mammalian Golgi 1,2-mannosidase which is a type II transmembrane protein. This protein catalyzes the hydrolysis of three terminal mannose residues from peptide-bound Man(9)-GlcNAc(2) oligosaccharides and belongs to family 47 of glycosyl hydrolases. [provided by RefSeq, Jul 2012]

113
ClinVar variants
23
Pathogenic / LP
0.11
pLI score
0
Active trials
Clinical Summary— MAN1A1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 85 VUS of 113 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.111
Z-score 3.86
OE 0.26 (0.15–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.51Z-score
OE missense 0.77 (0.70–0.85)
270 obs / 349.6 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.0.26 (0.15–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.70–0.85)
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.0.92
0≤1.21.6
LoF obs/exp: 8 / 31.3Missense obs/exp: 270 / 349.6Syn Z: 0.78

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic5
VUS85
Likely Benign2
Benign3
18
Pathogenic
5
Likely Pathogenic
85
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
5
0
5
VUS
0
82
3
0
85
Likely Benign
0
1
1
0
2
Benign
0
1
1
1
3
Total084281113

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

View in ClinVar →

Protein Context — Lollipop Plot

MAN1A1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
α-Mannosidase I Protein Expression in Peripheral Blood Mononuclear Cells Is Upregulated During Hepatitis B Virus Infection.
Jiang L et al.·Viral Immunol
2016
Plasma Proteomic Profiles Among White and African American Individuals With Monoclonal Gammopathy of Unknown Significance (MGUS) and Multiple Myeloma (MM).
Varga C et al.·Clin Lymphoma Myeloma Leuk
2025
Gene expression pattern contributing to prognostic factors in childhood acute lymphoblastic leukemia.
Silveira VS et al.·Leuk Lymphoma
2013
Sweat Proteomics in Cystic Fibrosis: Discovering Companion Biomarkers for Precision Medicine and Therapeutic Development.
Burat B et al.·Cells
2022
The transcriptional profiling of glycogenes associated with hepatocellular carcinoma metastasis.
Liu T et al.·PLoS One
2014
High Mannose N-Glycans Promote Migration of Bone-Marrow-Derived Mesenchymal Stromal Cells.
Alonso-Garcia V et al.·Int J Mol Sci
2020
Identification of a Novel MAN1A1-ROS1 Fusion Gene Through mRNA-based Screening for Tyrosine Kinase Gene Aberrations in a Patient with Leiomyosarcoma.
Suehara Y et al.·Clin Orthop Relat Res
2021
A Fluorogenic Disaccharide Substrate for α-Mannosidases Enables High-Throughput Screening and Identification of an Inhibitor of the GH92 Virulence Factor from Streptococcus pneumoniae.
Bhosale S et al.·ACS Chem Biol
2023
Mannose glycosylation is an integral step for NIS localization and function in human breast cancer cells.
Rathod M et al.·J Cell Sci
2019
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