PHGDH

phosphoglycerate dehydrogenase

Basic information

Region (hg38): 1:119648410-119744218

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

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 (653 variants)
• not provided (84 variants)
• Neu-Laxova syndrome 1 (64 variants)
• Inborn genetic diseases (25 variants)
• not specified (9 variants)
• Neu-Laxova syndrome 1;PHGDH deficiency (5 variants)
• Epileptic encephalopathy;Seizure (2 variants)
• PHGDH deficiency;Neu-Laxova syndrome 1 (2 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.

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			2	194	3	199
missense		3	208	23		234
nonsense	19	2		1		22
start loss	2	1				3
frameshift	19	3	2			24
inframe indel			1			1
splice donor/acceptor (+/-2bp)		13	1			14
splice region			16	40		56
non coding			13	95	19	127
Total	40	22	227	313	22

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)
1-119711816-G-A		PHGDH deficiency	Uncertain significance (Jan 13, 2018)
1-119711840-G-A		PHGDH deficiency	Uncertain significance (Jan 12, 2018)
1-119711883-A-G		PHGDH deficiency • Neu-Laxova syndrome 1	Benign (Jul 08, 2021)
1-119711913-G-A			Likely benign (Mar 30, 2021)
1-119711922-G-C		PHGDH deficiency • Neu-Laxova syndrome 1	Benign (Jul 08, 2021)
1-119711944-T-C		PHGDH deficiency	Uncertain significance (Jan 12, 2018)
1-119712012-C-T		PHGDH deficiency	Uncertain significance (Jan 13, 2018)
1-119712023-A-C		PHGDH deficiency • Neu-Laxova syndrome 1	Pathogenic (May 01, 2023)
1-119712023-A-G		PHGDH deficiency	Pathogenic (Aug 29, 2023)
1-119712024-T-C		PHGDH deficiency • Neu-Laxova syndrome 1	Pathogenic/Likely pathogenic (Apr 11, 2023)
1-119712034-A-T		PHGDH deficiency	Likely benign (Nov 23, 2022)
1-119712035-A-G		PHGDH deficiency	Uncertain significance (Jul 05, 2022)
1-119712038-C-T		PHGDH deficiency	Likely benign (Sep 12, 2023)
1-119712042-G-C		PHGDH deficiency	Uncertain significance (Aug 30, 2021)
1-119712043-G-C		PHGDH deficiency	Likely benign (Aug 17, 2021)
1-119712044-A-T		PHGDH deficiency	Pathogenic (Sep 15, 2021)
1-119712046-A-T		PHGDH deficiency	Uncertain significance (Nov 27, 2021)
1-119712047-G-C		PHGDH deficiency	Uncertain significance (Jul 12, 2022)
1-119712052-C-T		PHGDH deficiency	Likely benign (Apr 20, 2021)
1-119712056-A-G		PHGDH deficiency	Uncertain significance (Aug 20, 2022)
1-119712057-G-T		PHGDH deficiency	Uncertain significance (Apr 30, 2022)
1-119712062-A-G		PHGDH deficiency • Neu-Laxova syndrome 1	Uncertain significance (Apr 11, 2023)
1-119712064-C-T		PHGDH deficiency	Likely benign (Jul 08, 2022)
1-119712070-C-T		PHGDH deficiency	Likely benign (Dec 29, 2023)

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