PHGDH

phosphoglycerate dehydrogenase

Basic information

Region (hg38): 1:119648411-119744218

Links

ENSG00000092621NCBI:26227OMIM:606879HGNC:8923Uniprot:O43175AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • PHGDH deficiency (Definitive), mode of inheritance: AR
  • Neu-Laxova syndrome (Supportive), mode of inheritance: AR
  • PHGDH deficiency (Supportive), mode of inheritance: AR
  • PHGDH deficiency (Strong), mode of inheritance: AR
  • neurometabolic disorder due to serine deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Phosphoglycerate dehydrogenase deficiencyARBiochemicalAmino acid therapy (eg, with L-serine, glycine) has been reported as beneficial for at least some clinical parameters, especially if early treatment is inititiated (reports include benefits to prenatal treatment)Biochemical; Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary8739971 ; 8758134; 11055895; 12118526; 15610810; 16763900; 19235232; 20196394; 21113737; 24836451; 28135894

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHGDH gene.

  • PHGDH deficiency (51 variants)
  • Neu-Laxova syndrome 1 (2 variants)
  • Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHGDH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
223
clinvar
3
clinvar
227
missense
1
clinvar
3
clinvar
213
clinvar
27
clinvar
244
nonsense
22
clinvar
2
clinvar
1
clinvar
25
start loss
2
clinvar
1
clinvar
3
frameshift
27
clinvar
3
clinvar
2
clinvar
32
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
16
clinvar
1
clinvar
17
splice region
16
47
63
non coding
13
clinvar
133
clinvar
21
clinvar
167
Total 52 25 231 384 24

Highest pathogenic variant AF is 0.0000131

Variants in PHGDH

This is a list of pathogenic ClinVar variants found in the PHGDH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-119711801-G-A PHGDH deficiency Uncertain significance (Jan 13, 2018)292296
1-119711816-G-A PHGDH deficiency Uncertain significance (Jan 13, 2018)292297
1-119711840-G-A PHGDH deficiency Uncertain significance (Jan 12, 2018)292298
1-119711883-A-G PHGDH deficiency • Neu-Laxova syndrome 1 Benign (Jul 08, 2021)292299
1-119711913-G-A Likely benign (Mar 30, 2021)1300431
1-119711922-G-C PHGDH deficiency • Neu-Laxova syndrome 1 Benign (Jul 08, 2021)292300
1-119711944-T-C PHGDH deficiency Uncertain significance (Jan 12, 2018)292301
1-119712012-C-T PHGDH deficiency Uncertain significance (Jan 13, 2018)292302
1-119712023-A-C PHGDH deficiency • Neu-Laxova syndrome 1 Pathogenic (May 01, 2023)2169478
1-119712023-A-G PHGDH deficiency Pathogenic (Aug 29, 2023)1414498
1-119712024-T-C PHGDH deficiency • Neu-Laxova syndrome 1 Pathogenic/Likely pathogenic (Apr 11, 2023)1331415
1-119712034-A-T PHGDH deficiency Likely benign (Nov 23, 2022)2030302
1-119712035-A-G PHGDH deficiency Uncertain significance (Jul 05, 2022)1431710
1-119712038-C-T PHGDH deficiency Likely benign (Sep 12, 2023)1114490
1-119712042-G-C PHGDH deficiency Uncertain significance (Aug 30, 2021)1494191
1-119712043-G-C PHGDH deficiency Likely benign (Aug 17, 2021)1578617
1-119712044-A-T PHGDH deficiency Pathogenic (Sep 15, 2021)1393177
1-119712046-A-T PHGDH deficiency Uncertain significance (Nov 27, 2021)1473047
1-119712047-G-C PHGDH deficiency Uncertain significance (Jul 12, 2022)1424885
1-119712052-C-T PHGDH deficiency Likely benign (Apr 20, 2021)1539416
1-119712056-A-G PHGDH deficiency Uncertain significance (Aug 20, 2022)1393987
1-119712057-G-T PHGDH deficiency Uncertain significance (Apr 30, 2022)2129061
1-119712062-A-G PHGDH deficiency • Neu-Laxova syndrome 1 Uncertain significance (Apr 11, 2023)452805
1-119712064-C-T PHGDH deficiency Likely benign (Jul 08, 2022)1949450
1-119712070-C-T PHGDH deficiency Likely benign (Dec 29, 2023)1138023

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PHGDHprotein_codingprotein_codingENST00000369409 1284418
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0001330.9921257220261257480.000103
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2072953050.9670.00001853421
Missense in Polyphen98105.970.924771184
Synonymous-0.5721391311.060.000008281151
Loss of Function2.341021.80.4590.00000104260

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00005780.0000578
Ashkenazi Jewish0.000.00
East Asian0.0001720.000163
Finnish0.000.00
European (Non-Finnish)0.0001610.000158
Middle Eastern0.0001720.000163
South Asian0.00009800.0000980
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Catalyzes the reversible oxidation of 3-phospho-D- glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate. {ECO:0000269|PubMed:11751922, ECO:0000269|PubMed:25406093}.;
Disease
DISEASE: Phosphoglycerate dehydrogenase deficiency (PHGDHD) [MIM:601815]: An autosomal recessive inborn error of L-serine biosynthesis, clinically characterized by congenital microcephaly, psychomotor retardation, and seizures. {ECO:0000269|PubMed:11055895, ECO:0000269|PubMed:19235232}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neu-Laxova syndrome 1 (NLS1) [MIM:256520]: A lethal, autosomal recessive multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, limb deformities, hypoplastic lungs, edema, and central nervous system anomalies including lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum. Abnormal facial features include severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears. {ECO:0000269|PubMed:24836451}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Glycine, serine and threonine metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);Trans-sulfuration and one carbon metabolism;Pathways in clear cell renal cell carcinoma;serine biosynthesis (phosphorylated route);Metabolism of amino acids and derivatives;Glycine Serine metabolism;Metabolism;serine and glycine biosynthesis;Amino acid synthesis and interconversion (transamination);Serine biosynthesis (Consensus)

Recessive Scores

pRec
0.562

Intolerance Scores

loftool
0.151
rvis_EVS
-0.62
rvis_percentile_EVS
17.36

Haploinsufficiency Scores

pHI
0.249
hipred
Y
hipred_score
0.807
ghis
0.537

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.958

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Phgdh
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
cellular amino acid metabolic process;glutamine metabolic process;glycine metabolic process;L-serine biosynthetic process;threonine metabolic process;brain development;gamma-aminobutyric acid metabolic process;regulation of gene expression;taurine metabolic process;spinal cord development;glial cell development;neural tube development;electron transport chain;neuron projection development;G1 to G0 transition
Cellular component
cytosol;myelin sheath;extracellular exosome
Molecular function
phosphoglycerate dehydrogenase activity;electron transfer activity;L-malate dehydrogenase activity;NAD binding