PSPH

phosphoserine phosphatase, the group of HAD Asp-based non-protein phosphatases

Basic information

Region (hg38): 7:56011050-56051604

Previous symbols: [ "PSP" ]

Links

ENSG00000146733 ∙ NCBI:5723 ∙ OMIM:172480 ∙ HGNC:9577 ∙ Uniprot:P78330 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• PSPH deficiency (Definitive), mode of inheritance: AR
• Neu-Laxova syndrome 1 (Definitive), mode of inheritance: AR
• PSPH deficiency (Moderate), mode of inheritance: AR
• PSPH deficiency (Strong), mode of inheritance: AR
• PSPH deficiency (Supportive), mode of inheritance: AR
• neurometabolic disorder due to serine deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Phosphoserine phosphatase deficiency	AR	Biochemical	Medical treatment (eg, with L-serine, glycine) has been reported as beneficial in terms of both biochemical parameters and clinical manifestations (head growth)	Biochemical; Neurologic	9222972; 14673469; 16763900; 19963421; 25080166

ClinVar

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

• Deficiency of phosphoserine phosphatase (145 variants)
• Inborn genetic diseases (13 variants)
• not provided (11 variants)
• not specified (4 variants)
• Amelogenesis imperfecta (1 variants)
• Seizure;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSPH 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	19	6	27
missense			46	5	5	56
nonsense		1	1			2
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1	1		2
splice region			5	2	1	8
non coding			35	16	6	57
Total	0	1	86	41	17

Variants in PSPH

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

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

Position	Type	Phenotype	Significance	ClinVar
7-56011113-T-G		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011174-C-T		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011272-G-A		Deficiency of phosphoserine phosphatase	Benign (Jan 13, 2018)
7-56011305-G-A		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 13, 2018)
7-56011356-C-T		Deficiency of phosphoserine phosphatase	Benign (Jan 13, 2018)
7-56011391-T-C		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011401-T-C		Deficiency of phosphoserine phosphatase	Benign (Jan 13, 2018)
7-56011421-C-T		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 13, 2018)
7-56011445-C-T		Deficiency of phosphoserine phosphatase	Likely benign (Jan 13, 2018)
7-56011446-G-A		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 13, 2018)
7-56011453-T-C		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 13, 2018)
7-56011484-G-A		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011485-C-T		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011528-C-CA		Deficiency of phosphoserine phosphatase	Uncertain significance (Jun 14, 2016)
7-56011559-A-G		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011605-G-A		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011716-T-G		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011740-T-C		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011750-C-T		Deficiency of phosphoserine phosphatase	Uncertain significance (Jan 12, 2018)
7-56011751-G-A		Deficiency of phosphoserine phosphatase	Benign (Jan 12, 2018)
7-56011754-A-G		Deficiency of phosphoserine phosphatase	Benign (Apr 27, 2017)
7-56011767-C-G		Deficiency of phosphoserine phosphatase	Uncertain significance (Nov 29, 2022)
7-56011767-C-T		Deficiency of phosphoserine phosphatase • Inborn genetic diseases	Uncertain significance (Jan 25, 2024)
7-56011768-T-C		Deficiency of phosphoserine phosphatase	Likely benign (Oct 13, 2023)
7-56011774-T-C			Likely benign (Apr 06, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSPH	protein_coding	protein_coding	ENST00000395471	5	40554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000967	0.825	125710	0	36	125746	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.777	101	126	0.805	0.00000657	1451
Missense in Polyphen		32	48.594	0.65852		594
Synonymous	0.352	44	47.1	0.935	0.00000253	444
Loss of Function	1.16	6	9.96	0.602	5.87e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00115	0.00116
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the last step in the biosynthesis of serine from carbohydrates. The reaction mechanism proceeds via the formation of a phosphoryl-enzyme intermediates. {ECO:0000269|PubMed:12777757}.
• Disease: DISEASE: Phosphoserine phosphatase deficiency (PSPHD) [MIM:614023]: An autosomal recessive disorder that results in pre- and postnatal growth retardation, moderate psychomotor retardation and facial features suggestive of Williams syndrome. {ECO:0000269|PubMed:14673469}. 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)

Intolerance Scores

• loftool: 0.282
• rvis_EVS: 0.42
• rvis_percentile_EVS: 76.81

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.739
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.975

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psph
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: L-serine metabolic process;L-serine biosynthetic process;response to mechanical stimulus;dephosphorylation;response to nutrient levels;response to testosterone
• Cellular component: cytoplasm;cytosol;neuron projection
• Molecular function: magnesium ion binding;phosphoserine phosphatase activity;calcium ion binding;phosphatase activity;protein homodimerization activity