GMPPB

Chr 3AR

GDP-mannose pyrophosphorylase B

NCBI Gene: 29925ENSG00000173540UniProt: Q9Y5P6

Catalytic subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex (PubMed:33986552). Catalyzes the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids (PubMed:33986552). Can catalyze the reverse reaction in vitro (PubMed:33986552). Together with GMPPA regulates GDP-alpha-D-mannose levels (PubMed:33986552)

Primary Disease Associations & Inheritance

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14MIM #615350
AR
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14MIM #615351
AR
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14MIM #615352
AR
489
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— GMPPB
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 215 VUS of 489 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
1.09LOEUF
pLI 0.000
Z-score 1.28
OE 0.67 (0.43–1.09)
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.
1.02Z-score
OE missense 0.82 (0.73–0.92)
205 obs / 250.4 exp
Tolerant

Mild missense constraint

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.0.67 (0.43–1.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.73–0.92)
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.1.06
0≤1.21.6
LoF obs/exp: 12 / 17.8Missense obs/exp: 205 / 250.4Syn Z: -0.45

ClinVar Variant Classifications

489 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic39
VUS215
Likely Benign161
Benign11
Conflicting17
32
Pathogenic
39
Likely Pathogenic
215
VUS
161
Likely Benign
11
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
5
17
0
32
Likely Pathogenic
18
17
4
0
39
VUS
2
192
18
3
215
Likely Benign
1
5
61
94
161
Benign
0
4
6
1
11
Conflicting
—17
Total3122310698475

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

View in ClinVar →

Protein Context — Lollipop Plot

GMPPB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GMPPB-related muscular dystrophy-dystroglycanopathy

definitive
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14

MIM #615350

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14

MIM #615351

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14

MIM #615352

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort.
Polavarapu K et al.·Brain
2024Cohort
Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients.
Song D et al.·Clin Genet
2021Cohort
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Neurogenetic fetal akinesia and arthrogryposis: genetics, expanding genotype-phenotypes and functional genomics.
Ravenscroft G et al.·J Med Genet
2021Functional
Integrative multi-omics analysis reveal novel therapeutic targets for glioblastoma.
Li J et al.·Int J Surg
2025
Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis.
Theuriet J et al.·Brain
2024
GDP-Mannose Pyrophosphorylase B (GMPPB)-Related Disorders.
Chompoopong P et al.·Genes (Basel)
2023Review
Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.
Sframeli M et al.·Neuromuscul Disord
2017Cohort
GMPPB-CDG Results in Lysosomal Dysfunction and Acid Alpha-Glucosidase Deficiency.
Damiano C et al.·J Inherit Metab Dis
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools