PSAT1

phosphoserine aminotransferase 1

Basic information

Region (hg38): 9:78297124-78330093

Links

ENSG00000135069 ∙ NCBI:29968 ∙ OMIM:610936 ∙ HGNC:19129 ∙ Uniprot:Q9Y617 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Neu-Laxova syndrome 1 (Strong), mode of inheritance: AR
• Neu-Laxova syndrome 2 (Moderate), mode of inheritance: AR
• Neu-Laxova syndrome (Supportive), mode of inheritance: AR
• PSAT deficiency (Supportive), mode of inheritance: AD
• PSAT 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
Phosphoserine aminotransferase deficiency	AR	Biochemical	Medical treatment (eg, with serine and glycine) can lead to improved outcomes, and early initiation of treatment may be beneficial	Biochemical; Craniofacial; Musculoskeletal; Neurologic	17436247; 25152457; 29269105

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSAT1 gene.

• not provided (263 variants)
• Neu-Laxova syndrome 2 (246 variants)
• PSAT deficiency (60 variants)
• PSAT1-Related Disorders (2 variants)
• High myopia (1 variants)
• Microcephaly (1 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 PSAT1 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				51	4	55
missense	1	2	112	2		117
nonsense	6	3				9
start loss						0
frameshift	8		1			9
inframe indel						0
splice donor/acceptor (+/-2bp)		5	1			6
splice region			6	10		16
non coding			18	31	36	85
Total	15	10	132	84	40

Highest pathogenic variant AF is 0.0000986

Variants in PSAT1

This is a list of pathogenic ClinVar variants found in the PSAT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-78297185-T-G		PSAT deficiency	Uncertain significance (Jan 13, 2018)
9-78297199-G-C		PSAT deficiency • Neu-Laxova syndrome 2	Benign (Oct 25, 2021)
9-78297214-G-A		Neu-Laxova syndrome 2	Uncertain significance (Feb 10, 2022)
9-78297214-G-T		PSAT deficiency • Neu-Laxova syndrome 2	Uncertain significance (Nov 05, 2021)
9-78297217-G-A		Neu-Laxova syndrome 2	Uncertain significance (Jul 12, 2022)
9-78297217-G-T		Neu-Laxova syndrome 2	Uncertain significance (Dec 14, 2022)
9-78297219-C-T		Neu-Laxova syndrome 2	Likely benign (Aug 20, 2021)
9-78297220-C-G		PSAT deficiency	Uncertain significance (Jan 13, 2018)
9-78297243-G-T		Neu-Laxova syndrome 2	Likely benign (Dec 12, 2023)
9-78297247-G-A		Neu-Laxova syndrome 2	Uncertain significance (Mar 19, 2022)
9-78297247-GGTCCCGCCAAGCTGCCGCACTCAGTAA-G		Neu-Laxova syndrome 2	Likely pathogenic (Dec 12, 2023)
9-78297253-G-A		Neu-Laxova syndrome 2	Uncertain significance (Mar 15, 2021)
9-78297253-G-C		PSAT deficiency • Microcephaly • Neu-Laxova syndrome 2	Uncertain significance (Jul 27, 2022)
9-78297254-C-T		PSAT deficiency	Uncertain significance (Jul 03, 2017)
9-78297259-C-T		Neu-Laxova syndrome 2	Likely benign (Apr 16, 2022)
9-78297264-G-A		PSAT deficiency • Neu-Laxova syndrome 2	Conflicting classifications of pathogenicity (Apr 19, 2022)
9-78297264-G-T		Neu-Laxova syndrome 2	Likely benign (May 25, 2023)
9-78297265-C-G		PSAT deficiency • Neu-Laxova syndrome 2	Uncertain significance (Jan 24, 2023)
9-78297278-C-G		Neu-Laxova syndrome 2	Likely benign (Jan 03, 2024)
9-78297279-C-G		Neu-Laxova syndrome 2	Likely benign (Jun 14, 2021)
9-78297280-C-T		Neu-Laxova syndrome 2	Likely benign (Feb 24, 2023)
9-78297290-C-A		Neu-Laxova syndrome 2	Likely benign (Aug 03, 2023)
9-78297290-C-T		Neu-Laxova syndrome 2	Uncertain significance (Mar 02, 2021)
9-78297481-C-G			Benign (Nov 12, 2018)
9-78300476-G-A			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSAT1	protein_coding	protein_coding	ENST00000376588	9	32951

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.06e-8	0.326	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.413	185	202	0.918	0.0000110	2425
Missense in Polyphen		54	67.279	0.80262		835
Synonymous	0.501	73	78.7	0.928	0.00000477	715
Loss of Function	0.713	14	17.2	0.815	8.21e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000273	0.000264
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reversible conversion of 3- phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4- phosphonooxybutanoate to phosphohydroxythreonine. {ECO:0000250|UniProtKB:P10658}.
• Disease: DISEASE: Neu-Laxova syndrome 2 (NLS2) [MIM:616038]: A form of Neu- Laxova syndrome, 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. These include 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:25152457}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycine, serine and threonine metabolism - Homo sapiens (human);Vitamin B6 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);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;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;Vitamin B6 metabolism;Amino acid synthesis and interconversion (transamination);Serine biosynthesis (Consensus)

Recessive Scores

• pRec: 0.484

Intolerance Scores

• loftool: 0.261
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.677
• ghis: 0.503

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.978

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psat1
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region 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)

Gene ontology

• Biological process: L-serine biosynthetic process;pyridoxine biosynthetic process
• Cellular component: cytosol;extracellular exosome
• Molecular function: O-phospho-L-serine:2-oxoglutarate aminotransferase activity