PHGDH
Basic information
Region (hg38): 1:119648411-119744218
Links
Phenotypes
GenCC
Source:
- 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:
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
- 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 | 223 | 227 | ||||
missense | 213 | 27 | 244 | |||
nonsense | 22 | 25 | ||||
start loss | 3 | |||||
frameshift | 27 | 32 | ||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 16 | 17 | ||||
splice region | 16 | 47 | 63 | |||
non coding | 13 | 133 | 21 | 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) | ||
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:
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:
- 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