PHGDH
Chr 1ARphosphoglycerate dehydrogenase
Also known as: 3-PGDH, 3PGDH, HEL-S-113, NLS, NLS1, PDG, PGAD, PGD
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.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 4 | 2 | 7 | 0 | 13 |
Likely Pathogenic | 16 | 0 | 0 | 0 | 16 |
VUS | 0 | 61 | 11 | 6 | 78 |
Likely Benign | 0 | 0 | 46 | 35 | 81 |
Benign | 0 | 0 | 2 | 0 | 2 |
| Total | 20 | 63 | 66 | 41 | 190 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PHGDH · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools