MAN2B2

Chr 4AR

mannosidase alpha class 2B member 2

Also known as: CDG1EE, EpMAN

NCBI Gene: 23324 ENSG00000013288 UniProt: Q9Y2E5 OMIM: 618899

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables mannan endo-1,6-alpha-mannosidase activity and mannosyl-oligosaccharide 1,6-alpha-mannosidase activity. Involved in glycoprotein catabolic process and oligosaccharide catabolic process. Located in extracellular exosome. Is active in lysosomal lumen. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation type 1EE with or without immunodeficiencyMIM #621140

Clinical highlights

Gene–disease validity (ClinGen)

Limited · MAN2B2 deficiency · AR · ClinGen 2024

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.01

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.01LOEUF

pLI 0.000

Z-score 1.48

OE 0.78 (0.61–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.26Z-score

OE missense 1.03 (0.96–1.09)

688 obs / 669.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.61–1.01)

0≤0.351.4

Missense OE?1.03 (0.96–1.09)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 41 / 52.6Missense obs/exp: 688 / 669.3Syn Z: 0.44

Background carrier burden — how many people carry a rare variant somewhere in MAN2B2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 24

1,438 rare PASS variants

Rare truncating (LoF)

1 in 390

232 rare PASS variants

Rare synonymous (reference)

1 in 48

590 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAN2B2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 33	1 in 1,000
South Asian	~43k	1 in 18	1 in 190
Remaining (unassigned)	~30k	1 in 20	1 in 280
European (Finnish)	~27k	1 in 89	1 in 4,700
Admixed American	~22k	1 in 25	1 in 400
African / African American	~21k	1 in 24	1 in 270
East Asian	~20k	1 in 23	1 in 470
Ashkenazi Jewish	~13k	1 in 77	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 30	1 in 570

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 19 coding exons well covered in gnomAD exomes and genomes.? see exons ↓