PHGDH

phosphoglycerate dehydrogenase

Basic information

Region (hg38): 1:119648411-119744218

Links

ENSG00000092621

∙ NCBI:26227 ∙ OMIM:606879 ∙ HGNC:8923 ∙ Uniprot:O43175 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
Neu-Laxova syndrome 1 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Phosphoglycerate dehydrogenase deficiency	AR	Biochemical	Amino 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; Pulmonary	8739971 ; 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 (807 variants)
not_provided (95 variants)
Neu-Laxova_syndrome_1 (77 variants)
Inborn_genetic_diseases (63 variants)
not_specified (19 variants)
PHGDH-related_disorder (13 variants)
Epileptic_encephalopathy (2 variants)
Seizure (2 variants)
Neurometabolic_disorder_due_to_serine_deficiency (1 variants)
See_cases (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. These statistics are base on transcript: NM_000006623.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	267 clinvar	2 clinvar	277
missense	3 clinvar	13 clinvar	257 clinvar	11 clinvar		284
nonsense	18 clinvar	8 clinvar				26
start loss	2	1				3
frameshift	26 clinvar	9 clinvar	2 clinvar			37
splice donor/acceptor (+/-2bp)		16 clinvar	1 clinvar			17
Total	49	47	268	278	2

Highest pathogenic variant AF is 0.0000638288

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHGDH	protein_coding	protein_coding	ENST00000369409	12	84418

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000133	0.992	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.207	295	305	0.967	0.0000185	3421
Missense in Polyphen		98	105.97	0.92477		1184
Synonymous	-0.572	139	131	1.06	0.00000828	1151
Loss of Function	2.34	10	21.8	0.459	0.00000104	260

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000172	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000161	0.000158
Middle Eastern	0.000172	0.000163
South Asian	0.0000980	0.0000980
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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