PMM2

Chr 16

phosphomannomutase 2

Also known as: CDG1, CDG1a, CDGS, PMI, PMI1, PMM 2

This protein catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is essential for GDP-mannose synthesis and subsequent dolichol-P-oligosaccharide production required for glycoprotein biosynthesis. Autosomal recessive mutations cause congenital disorder of glycosylation type Ia through defects in glycoprotein biosynthesis. The pathogenic mechanism involves dominant-negative effects that disrupt normal protein glycosylation pathways.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 1.88
Clinical SummaryPMM2
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Gene-Disease Validity (ClinGen)
hyperinsulinemic hypoglycemia with polycystic kidney disease · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — PMM2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.88LOEUF
pLI 0.000
Z-score -1.51
OE 1.41 (1.001.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.39Z-score
OE missense 1.33 (1.181.50)
186 obs / 139.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.41 (1.001.88)
00.351.4
Missense OE1.33 (1.181.50)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 22 / 15.6Missense obs/exp: 186 / 139.8Syn Z: -1.24
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePMM2-related congenital disorder of glycosylationLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.5367th %ile
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PMM2 · 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.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Congenital Hyperinsulinism: Diagnosis and Treatment Update.
Demirbilek H et al.·J Clin Res Pediatr Endocrinol
2017Review
Renal involvement in PMM2-CDG, a mini-review.
Altassan R et al.·Mol Genet Metab
2018Review
Genotype-Phenotype Correlations in PMM2-CDG.
Vaes L et al.·Genes (Basel)
2021
Top 5 results · since 2015Search PubMed ↗