PHGDH
Phosphoglycerate Dehydrogenase: A Key Enzyme in Serine Biosynthesis and Disease
Gene Information Card
| Symbol | PHGDH |
|---|---|
| Full Name | Phosphoglycerate Dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 1p12 |
| NCBI Gene ID | 26227 ncbi.nlm.nih.gov/gene/26227 |
| Ensembl ID | ENSG00000092621 |
| UniProt ID | O43175 |
| OMIM ID | 606879 |
| HGNC ID | 8923 |
| Aliases | 3-PGDH, 3PGDH, PGD, PGDH, SERA |
Description
The PHGDH gene encodes phosphoglycerate dehydrogenase, the first and rate-limiting enzyme in the phosphorylated pathway of L-serine biosynthesis. This enzyme catalyzes the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate using NAD+/NADH as a cofactor. PHGDH is essential for cellular serine production, which is critical for protein synthesis, nucleotide metabolism, and lipid biosynthesis. Alterations in PHGDH expression and function are linked to metabolic disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| PHGDH deficiency (Neu-Laxova syndrome) | Loss-of-function mutations impair serine biosynthesis, leading to severe neurological and developmental abnormalities. | OMIM #606879; ClinVar |
| Serine deficiency disorders | Reduced PHGDH activity causes low serine levels, affecting brain development and function. | OMIM #606879; NCBI Gene |
| Breast cancer | PHGDH amplification and overexpression increase serine synthesis, supporting cancer cell proliferation and survival. | COSMIC; NCBI PubMed |
| Melanoma | PHGDH upregulation promotes tumor growth by enhancing serine metabolism and redox balance. | COSMIC; NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 10.2 | High |
| Testis | 8.9 | Medium |
| Brain | 6.3 | Medium |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression in embryonic kidney cells |
| MCF7 | 11.8 | Breast cancer cell line with PHGDH amplification |
| A549 | 7.2 | Lung cancer cell line with moderate expression |
| HepG2 | 9.5 | Liver cancer cell line with high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of function; associated with PHGDH deficiency |
| c.403C>T (p.Arg135Trp) | Missense | Rare | Loss of function; reduces enzyme activity |
| c.1279G>A (p.Val427Met) | Missense | Rare | Uncertain significance; reported in ClinVar |
| Amplification | Copy number gain | Common in breast cancer | Gain of function; increases serine synthesis |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., p.Met1?, p.Arg135Trp) reduce or abolish enzyme activity, leading to serine deficiency and neurological disorders.
Gain of Function (GOF)
Gene amplification and overexpression in cancers (e.g., breast cancer, melanoma) enhance serine biosynthesis, promoting tumor growth.
Dominant Negative (DN)
No dominant-negative mutations have been reported for PHGDH.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004617 - phosphoglycerate dehydrogenase activity | • GO:0006564 - L-serine biosynthetic process |
| • GO:0005737 - cytoplasm | • GO:0005829 - cytosol |
| • GO:0055114 - oxidation-reduction process |
Pathways
• Serine biosynthesis (Reactome: R-HSA-71291)
• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)
• Glycine
• serine and threonine metabolism (KEGG: hsa00260)
Protein Summary
Phosphoglycerate dehydrogenase (PHGDH) is a 533-amino acid protein that forms a homotetramer. It contains a nucleotide-binding domain and a substrate-binding domain. The enzyme uses NAD+/NADH as a cofactor to catalyze the reversible oxidation of 3-phosphoglycerate to 3-phosphohydroxypyruvate. PHGDH is the first committed step in the phosphorylated serine biosynthesis pathway. Its activity is regulated by serine levels via feedback inhibition. Overexpression in cancer cells supports proliferation by providing serine for macromolecule synthesis and maintaining redox balance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHGDH Knockout HEK293 Cell Line | EDJ-KQ3927 | Human | 26227 | Details Get a Quote |
| PHGDH Knockout A-549 Cell Line | EDJ-KQ26164 | Human | 26227 | Details Get a Quote |
| PHGDH Knockout HCT 116 Cell Line | EDJ-KQ26165 | Human | 26227 | Details Get a Quote |
| PHGDH Knockout HeLa Cell Line | EDJ-KQ24819 | Human | 26227 | Details Get a Quote |
| PHGDH Knockout PK-15 Cell Line | EDC08335 | Pig | 100144529 | Details Get a Quote |
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