MAN2A2

Chr 15

mannosidase alpha class 2A member 2

Also known as: MANA2X, alpha-MIIx

NCBI Gene: 4122 ENSG00000196547 UniProt: P49641 OMIM: 600988

MAN2A2 encodes an alpha-mannosidase that catalyzes the first committed step in converting high mannose to complex N-glycans in the Golgi apparatus. Mutations cause alpha-mannosidosis type II, a lysosomal storage disorder with autosomal recessive inheritance that presents with intellectual disability, hearing loss, skeletal abnormalities, and coarse facial features. The gene shows moderate constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable alpha-mannosidase activity. Predicted to be involved in N-glycan processing. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Limited · congenital disorder of glycosylation · AR · ClinGen 2025

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.000

Z-score 3.96

OE 0.45 (0.33–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.05Z-score

OE missense 0.89 (0.83–0.95)

650 obs / 729.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.33–0.62)

0≤0.351.4

Missense OE?0.89 (0.83–0.95)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 27 / 60.1Missense obs/exp: 650 / 729.8Syn Z: -1.45

Background carrier burden — how many people carry a rare variant somewhere in MAN2A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

1,607 rare PASS variants

Rare truncating (LoF)

1 in 920

197 rare PASS variants

Rare synonymous (reference)

1 in 62

628 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAN2A2. 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 43	1 in 970
South Asian	~43k	1 in 39	1 in 570
Remaining (unassigned)	~30k	1 in 32	1 in 1,900
European (Finnish)	~27k	1 in 93	1 in 740
Admixed American	~22k	1 in 36	1 in 790
African / African American	~21k	1 in 36	1 in 790
East Asian	~20k	1 in 38	1 in 510
Ashkenazi Jewish	~13k	1 in 87	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 33	1 in 350

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 22 coding exons well covered in gnomAD exomes and genomes.? see exons ↓