GMPPB

Chr 3AR

GDP-mannose pyrophosphorylase B

Also known as: LGMDR19, MDDGA14, MDDGB14, MDDGC14

The protein catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, which is essential for N-linked oligosaccharide production. Biallelic mutations cause autosomal recessive muscular dystrophy-dystroglycanopathy with a spectrum ranging from severe congenital forms with brain and eye anomalies (type A) to milder limb-girdle presentations (type C). The pathogenic mechanism involves defective glycosylation of dystroglycan due to impaired GDP-mannose synthesis.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 1.093 OMIM phenotypes
Clinical SummaryGMPPB
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Gene-Disease Validity (ClinGen)
myopathy caused by variation in GMPPB · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.09LOEUF
pLI 0.000
Z-score 1.28
OE 0.67 (0.431.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.02Z-score
OE missense 0.82 (0.730.92)
205 obs / 250.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.431.09)
00.351.4
Missense OE0.82 (0.730.92)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 12 / 17.8Missense obs/exp: 205 / 250.4Syn Z: -0.45

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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