MAN2B1

Chr 19AR

mannosidase alpha class 2B member 1

Also known as: LAMAN, MANB

The encoded enzyme hydrolyzes terminal alpha-D-mannose residues in oligosaccharides during lysosomal degradation of N-linked glycoproteins. Mutations cause alpha-mannosidosis types I and II, a lysosomal storage disorder with autosomal recessive inheritance that affects multiple organ systems including the nervous system, skeleton, and immune system. This gene shows very low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.971 OMIM phenotype
Clinical SummaryMAN2B1
🧬
Gene-Disease Validity (ClinGen)
alpha-mannosidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 101 VUS of 200 total submissions
📖
GeneReview available — MAN2B1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.75
OE 0.75 (0.580.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.15Z-score
OE missense 0.87 (0.810.94)
557 obs / 638.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.580.97)
00.351.4
Missense OE0.87 (0.810.94)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 41 / 55.0Missense obs/exp: 557 / 638.9Syn Z: -0.15

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic24
VUS101
Likely Benign48
4
Pathogenic
24
Likely Pathogenic
101
VUS
48
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
0
0
4
Likely Pathogenic
24
0
0
0
24
VUS
0
80
10
11
101
Likely Benign
0
0
27
21
48
Benign
0
0
0
0
0
Total27813732177

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →