GMPPA

Chr 2AR

GDP-mannose pyrophosphorylase A

Also known as: AAMR

The protein functions as a regulatory subunit of the GDP-mannose pyrophosphorylase complex, reducing GMPPB catalytic activity and mediating allosteric feedback inhibition to regulate GDP-mannose levels required for N-linked oligosaccharide synthesis. Autosomal recessive mutations cause alacrima, achalasia, and impaired intellectual development syndrome through disrupted glycosylation pathways.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.941 OMIM phenotype
Clinical SummaryGMPPA
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Gene-Disease Validity (ClinGen)
alacrima, achalasia, and intellectual disability syndrome · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.79
OE 0.63 (0.430.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.21Z-score
OE missense 0.79 (0.700.89)
205 obs / 259.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.63 (0.430.94)
00.351.4
Missense OE0.79 (0.700.89)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 17 / 27.0Missense obs/exp: 205 / 259.9Syn Z: 0.50

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GMPPA · 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
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