GMPPA

Chr 2AR

GDP-mannose pyrophosphorylase A

Also known as: AAMR

NCBI Gene: 29926 ENSG00000144591 UniProt: Q96IJ6 OMIM: 615495

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is thought to encode a GDP-mannose pyrophosphorylase. This enzyme catalyzes the reaction which converts mannose-1-phosphate and GTP to GDP-mannose which is involved in the production of N-linked oligosaccharides. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Alacrima, achalasia, and impaired intellectual development syndromeMIM #615510

Clinical highlights

Gene-disease validity (ClinGen)

alacrima, achalasia, and intellectual disability syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.94

LOEUF

LOF

Mechanism· G2P

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GeneReview available — GMPPA