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 located in Golgi apparatus and membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.62

Clinical Summary— MAN2A2

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Gene-Disease Validity (ClinGen)

congenital disorder of glycosylation · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 177 VUS of 221 total submissions

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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

ClinVar Variant Classifications

221 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS177

Likely Benign13

Benign4

Conflicting1

Likely Pathogenic

177

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	1	0	0	2
VUS	0	177	0	0	177
Likely Benign	0	10	1	2	13
Benign	0	1	0	3	4
Conflicting	—				1
Total	1	189	1	5	197

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap MAN2A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →