MAN2B1

Chr 19AR

mannosidase alpha class 2B member 1

Also known as: LAMAN, MANB

NCBI Gene: 4125ENSG00000104774UniProt: O00754

This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Mannosidosis, alpha-, types I and IIMIM #248500
AR
1964
ClinVar variants
54
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MAN2B1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 Pathogenic / Likely Pathogenic· 126 VUS of 1964 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.
0.97LOEUF
pLI 0.000
Z-score 1.75
OE 0.75 (0.58–0.97)
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.
1.15Z-score
OE missense 0.87 (0.81–0.94)
557 obs / 638.9 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.0.75 (0.58–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.81–0.94)
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.1.01
0≤1.21.6
LoF obs/exp: 41 / 55.0Missense obs/exp: 557 / 638.9Syn Z: -0.15

ClinVar Variant Classifications

1964 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic35
VUS126
Likely Benign293
Benign3
Conflicting1
19
Pathogenic
35
Likely Pathogenic
126
VUS
293
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
12
0
19
Likely Pathogenic
25
0
10
0
35
VUS
0
102
13
11
126
Likely Benign
0
1
151
141
293
Benign
0
0
3
0
3
Conflicting
—1
Total32103189152477

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

View in ClinVar →

Protein Context — Lollipop Plot

MAN2B1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MAN2B1-related lysosomal alpha-mannosidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkinSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mannosidosis, alpha-, types I and II

MIM #248500

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease.
Karayel O et al.·Cell Rep Med
2022
Alpha-mannosidosis.
Malm D et al.·Orphanet J Rare Dis
2008Review
MAN2B1 in immune system-related diseases, neurodegenerative disorders and cancers: functions beyond α-mannosidosis.
Han Y et al.·Expert Rev Mol Med
2024Review
Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation.
Borgwardt L et al.·Orphanet J Rare Dis
2015Clinical trial
Diagnosis of alpha-Mannosidosis: Practical approaches to reducing diagnostic delays in this ultra-rare disease.
Santoro L et al.·Mol Genet Metab
2024Review
α-mannosidosis diagnosis in Brazilian patients with MPS-like symptoms.
Marins M et al.·Orphanet J Rare Dis
2024Cohort
Molecular and cellular characterization of novel {alpha}-mannosidosis mutations.
Kuokkanen E et al.·Hum Mol Genet
2011
Single-cell hdWGCNA reveals a novel diagnostic model and signature genes of macrophages associated with chronic obstructive pulmonary disease.
Zhou X et al.·Inflamm Res
2025Functional
Long-term clinical evaluation of patients with alpha-mannosidosis - A multicenter study.
Köse E et al.·Eur J Med Genet
2024Cohort
Identification of Tumor Antigens and Immune Subtypes of Glioblastoma for mRNA Vaccine Development.
Lin H et al.·Front Immunol
2022
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