PHGDH

Chr 1AR

phosphoglycerate dehydrogenase

Also known as: 3-PGDH, 3PGDH, HEL-S-113, NLS, NLS1, PDG, PGAD, PGD

NCBI Gene: 26227 ENSG00000092621 UniProt: O43175 OMIM: 606879

The enzyme catalyzes the first step of L-serine biosynthesis by oxidizing 3-phospho-D-glycerate to 3-phosphonooxypyruvate, requiring NAD/NADH as a cofactor. Biallelic mutations cause autosomal recessive phosphoglycerate dehydrogenase deficiency and Neu-Laxova syndrome 1, both presenting with severe congenital microcephaly and developmental delay. The gene shows tolerance to loss-of-function variants (LOEUF 0.778), suggesting complete loss of enzyme function may be required for disease manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the enzyme which is involved in the early steps of L-serine synthesis in animal cells. L-serine is required for D-serine and other amino acid synthesis. The enzyme requires NAD/NADH as a cofactor and forms homotetramers for activity. Mutations in this gene have been found in a family with congenital microcephaly, psychomotor retardation and other symptoms. Multiple alternatively spliced transcript variants have been found, however the full-length nature of most are not known. [provided by RefSeq, Aug 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neu-Laxova syndrome 1MIM #256520

Phosphoglycerate dehydrogenase deficiencyMIM #601815

Clinical highlights

Gene-disease validity (ClinGen)

neurometabolic disorder due to serine deficiency · 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

183

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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