MAN2B2

Chr 4AR

mannosidase alpha class 2B member 2

Also known as: CDG1EE, EpMAN

The protein specifically cleaves terminal alpha 1,6-linked mannose residues on small core oligosaccharides during N-glycan degradation pathways. Mutations cause congenital disorder of glycosylation type 1EE with or without immunodeficiency, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (LOEUF 1.011), suggesting complete loss of function may be required for disease manifestation.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Congenital disorder of glycosylation type 1EE with or without immunodeficiencyMIM #621140
AR
0
Active trials
3
Pubs (1 yr)
92
P/LP submissions
3%
P/LP missense
1.01
LOEUF
Mechanism
Clinical SummaryMAN2B2
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Gene-Disease Validity (ClinGen)
MAN2B2 deficiency · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
92 unique Pathogenic / Likely Pathogenic· 247 VUS of 432 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.48
OE 0.78 (0.611.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.26Z-score
OE missense 1.03 (0.961.09)
688 obs / 669.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.78 (0.611.01)
00.351.4
Missense OE1.03 (0.961.09)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 41 / 52.6Missense obs/exp: 688 / 669.3Syn Z: 0.44

ClinVar Variant Classifications

432 submitted variants in ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic7
VUS247
Likely Benign38
Benign29
85
Pathogenic
7
Likely Pathogenic
247
VUS
38
Likely Benign
29
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
82
0
85
Likely Pathogenic
0
0
7
0
7
VUS
3
237
7
0
247
Likely Benign
1
23
0
14
38
Benign
0
5
17
7
29
Total426811321406

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

View in ClinVar →

Protein Context — Lollipop Plot

MAN2B2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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