PHGDH

Protein identityUniProt · HPA

UniProt accession

O43175

Gene

PHGDH

Ensembl

ENSG00000092621

Chromosome

1

Canonical length

533 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane,Cytosol

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

533 residues, UniProt reviewed canonical sequence.

>O43175|PHGDH
     1  MAFANLRKVL ISDSLDPCCR KILQDGGLQV VEKQNLSKEE LIAELQDCEG LIVRSATKVT
    61  ADVINAAEKL QVVGRAGTGV DNVDLEAATR KGILVMNTPN GNSLSAAELT CGMIMCLARQ
   121  IPQATASMKD GKWERKKFMG TELNGKTLGI LGLGRIGREV ATRMQSFGMK TIGYDPIISP
   181  EVSASFGVQQ LPLEEIWPLC DFITVHTPLL PSTTGLLNDN TFAQCKKGVR VVNCARGGIV
   241  DEGALLRALQ SGQCAGAALD VFTEEPPRDR ALVDHENVIS CPHLGASTKE AQSRCGEEIA
   301  VQFVDMVKGK SLTGVVNAQA LTSAFSPHTK PWIGLAEALG TLMRAWAGSP KGTIQVITQG
   361  TSLKNAGNCL SPAVIVGLLK EASKQADVNL VNAKLLVKEA GLNVTTSHSP AAPGEQGFGE
   421  CLLAVALAGA PYQAVGLVQG TTPVLQGLNG AVFRPEVPLR RDLPLLLFRT QTSDPAMLPT
   481  MIGLLAEAGV RLLSYQTSLV SDGETWHVMG ISSLLPSLEA WKQHVTEAFQ FHF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PHGDH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

161 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PHGDH.

Disease | AllUniProt

Conditions PHGDH is implicated in, by any mechanism.

• Phosphoglycerate dehydrogenase deficiency (PHGDHD) MIM:601815
• Neu-Laxova syndrome 1 (NLS1) MIM:256520

Disease | GeneticClinVar

97 pathogenic / likely-pathogenic of 948 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• PHGDH deficiency
• Neu-Laxova syndrome 1
• Autosomal recessive PHGDH-related disorders
• See cases
• PHGDH-related disorder

ReferencesPubMed · IEDB

Publications for PHGDH from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.78

gnomAD pLI

0

gnomAD missense Z

0.21

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• brain development
• G1 to G0 transition
• gamma-aminobutyric acid metabolic process
• glial cell development
• glutamine metabolic process
• glycine metabolic process
• L-serine biosynthetic process
• neural tube development
• neuron projection development
• regulation of gene expression
• spinal cord development
• taurine metabolic process
• threonine metabolic process

Molecular functions

• electron transfer activity
• L-malate dehydrogenase (NAD+) activity
• NAD binding
• phosphoglycerate dehydrogenase activity

Cellular components

• cytosol
• extracellular exosome

Protein domainsUniProt · Pfam · InterPro

• D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain
• D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain
• D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site 1
• D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site
• NAD(P)-binding domain superfamily
• D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain
• D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain
• D-3-phosphoglycerate dehydrogenase
• Allosteric substrate binding domain superfamily
• D-3-phosphoglycerate dehydrogenase, ASB domain
• D-3-phosphoglycerate dehydrogenase intervening domain

KeywordsUniProt

• Acetylation
• Amino-acid biosynthesis
• Isopeptide bond
• NAD
• Oxidoreductase
• Phosphoprotein
• Serine biosynthesis
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of PHGDH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATP5F1A
• EPN1