GMPPB

Chr 3AR

GDP-mannose pyrophosphorylase B

Also known as: LGMDR19, MDDGA14, MDDGB14, MDDGC14

NCBI Gene: 29925 ENSG00000173540 UniProt: Q9Y5P6 OMIM: 615320

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is thought to encode a GDP-mannose pyrophosphorylase. The encoded protein catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, a reaction involved in the production of N-linked oligosaccharides. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 1.093 OMIM phenotypes

Clinical Summary— GMPPB

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Gene-Disease Validity (ClinGen)

myopathy caused by variation in GMPPB · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

61 unique Pathogenic / Likely Pathogenic· 212 VUS of 476 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GMPPB

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

1.02Z-score

OE missense 0.82 (0.73–0.92)

205 obs / 250.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.43–1.09)

0≤0.351.4

Missense OE?0.82 (0.73–0.92)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 12 / 17.8Missense obs/exp: 205 / 250.4Syn Z: -0.45

ClinVar Variant Classifications

476 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23

Likely Pathogenic38

VUS212

Likely Benign161

Benign11

Conflicting18

Pathogenic

Likely Pathogenic

212

VUS

161

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	5	0	0	23
Likely Pathogenic	18	19	1	0	38
VUS	3	195	11	3	212
Likely Benign	2	5	60	94	161
Benign	0	4	6	1	11
Conflicting	—				18
Total	41	228	78	98	463

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap GMPPB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →