PMM2

Chr 16AR

phosphomannomutase 2

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

NCBI Gene: 5373ENSG00000140650UniProt: O15305

The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IaMIM #212065
AR
976
ClinVar variants
108
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PMM2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
108 Pathogenic / Likely Pathogenic· 135 VUS of 976 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.88LOEUF
pLI 0.000
Z-score -1.51
OE 1.41 (1.00–1.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.39Z-score
OE missense 1.33 (1.18–1.50)
186 obs / 139.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.41 (1.00–1.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.33 (1.18–1.50)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 22 / 15.6Missense obs/exp: 186 / 139.8Syn Z: -1.24

ClinVar Variant Classifications

976 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic72
VUS135
Likely Benign208
Benign25
Conflicting11
36
Pathogenic
72
Likely Pathogenic
135
VUS
208
Likely Benign
25
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
5
20
0
36
Likely Pathogenic
18
37
17
0
72
VUS
1
92
39
3
135
Likely Benign
0
0
93
115
208
Benign
0
0
25
0
25
Conflicting
—11
Total30134194118487

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

View 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.

Gene2Phenotype Curations

PMM2-related congenital disorder of glycosylation

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type Ia

MIM #212065

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Congenital Hyperinsulinism: Diagnosis and Treatment Update.
Demirbilek H et al.·J Clin Res Pediatr Endocrinol
2017Review
Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management.
Giri D et al.·J Pediatr Endocrinol Metab
2021Review
International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up.
Altassan R et al.·J Inherit Metab Dis
2019Natural history
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Mannose metabolism normalizes gut homeostasis by blocking the TNF-α-mediated proinflammatory circuit.
Xiao P et al.·Cell Mol Immunol
2023
Systematic proteome-wide Mendelian randomization using the human plasma proteome to identify therapeutic targets for lung adenocarcinoma.
Zhang L et al.·J Transl Med
2024
Renal involvement in PMM2-CDG, a mini-review.
Altassan R et al.·Mol Genet Metab
2018Review
New and potential strategies for the treatment of PMM2-CDG.
Gámez A et al.·Biochim Biophys Acta Gen Subj
2020Review
A comprehensive update of genotype-phenotype correlations in PMM2-CDG: insights from molecular and structural analyses.
Oliveira T et al.·Orphanet J Rare Dis
2025Review
Recognizable phenotypes in CDG.
Ferreira CR et al.·J Inherit Metab Dis
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PMM2 interacts with TRIM28 to recruit E2F4 and promote KIFC3-mediated tumor glycolysis and colorectal cancer progression.
Peng Z et al.·Oncogene
2026
A founder variant in Tunisian PMM2-CDG patients: An integrated clinical, radiological, biochemical, and genetic study.
Kraoua L et al.·Mol Genet Metab
2026Cohort
PMM2-CDG and the Role of Liver Transplantation as a Long-Term Solution: A Case Report.
Blasingame BA et al.·Pediatr Transplant
2026Case report
Exploring a Circulating miRNA Signature for PMM2-CDG: Initial Insights Toward Diagnosis, Stratification, and Monitoring.
Epifani F et al.·J Inherit Metab Dis
2025🔓 Open Access
Treatment of Single Patient With PMM2-Congenital Disorder of Glycosylation With Govorestat (AT-007), an Aldose Reductase Inhibitor.
Jalazo ER et al.·JIMD Rep
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools