PSAT1

Summary

PSAT1 (phosphoserine aminotransferase 1, HGNC:19129) is a protein-coding gene on chromosome 9q21.2, encoding Phosphoserine aminotransferase (Q9Y617). Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine.

This gene encodes a member of the class-V pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is a phosphoserine aminotransferase and decreased expression may be associated with schizophrenia. Mutations in this gene are also associated with phosphoserine aminotransferase deficiency. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 1, 3, and 8.

Source: NCBI Gene 29968 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurometabolic disorder due to serine deficiency (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 530 total — 24 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 71
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_058179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19129
Approved symbol	PSAT1
Name	phosphoserine aminotransferase 1
Location	9q21.2
Locus type	gene with protein product
Status	Approved
Aliases	PSA, PSAT
Ensembl gene	ENSG00000135069
Ensembl biotype	protein_coding
OMIM	610936
Entrez	29968

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000347159, ENST00000376588, ENST00000906293, ENST00000906294, ENST00000906295, ENST00000906296, ENST00000916770, ENST00000916771, ENST00000916772, ENST00000916773, ENST00000916774

RefSeq mRNA: 2 — MANE Select: NM_058179 NM_021154, NM_058179

CCDS: CCDS6659, CCDS6660

Canonical transcript exons

ENST00000376588 — 9 exons

Exon	Start	End
ENSE00000917601	78301954	78302023
ENSE00000917602	78304735	78304940
ENSE00000917603	78306314	78306486
ENSE00000917604	78308414	78308583
ENSE00000917605	78317676	78317804
ENSE00001024259	78328051	78328188
ENSE00001270829	78300602	78300662
ENSE00001858489	78328981	78330093
ENSE00003842343	78297125	78297270

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 93.7867 / max 1218.7888, expressed in 1708 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97022	77.3462	1698
97023	16.4404	1346

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.33	gold quality
inferior vagus X ganglion	UBERON:0005363	98.38	gold quality
corpus epididymis	UBERON:0004359	98.37	gold quality
subthalamic nucleus	UBERON:0001906	98.09	gold quality
lateral globus pallidus	UBERON:0002476	98.08	gold quality
superior vestibular nucleus	UBERON:0007227	97.97	gold quality
ganglionic eminence	UBERON:0004023	97.95	gold quality
amygdala	UBERON:0001876	97.89	gold quality
ventral tegmental area	UBERON:0002691	97.71	gold quality
embryo	UBERON:0000922	97.54	gold quality
caudate nucleus	UBERON:0001873	97.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.39	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.31	gold quality
spinal cord	UBERON:0002240	97.26	gold quality
nucleus accumbens	UBERON:0001882	97.24	gold quality
corpus callosum	UBERON:0002336	97.00	gold quality
right lobe of liver	UBERON:0001114	96.88	gold quality
temporal lobe	UBERON:0001871	96.81	gold quality
Ammon’s horn	UBERON:0001954	96.73	gold quality
right adrenal gland cortex	UBERON:0035827	96.59	gold quality
putamen	UBERON:0001874	96.58	gold quality
pigmented layer of retina	UBERON:0001782	96.57	gold quality
pons	UBERON:0000988	96.44	gold quality
endothelial cell	CL:0000115	96.32	gold quality
substantia nigra pars compacta	UBERON:0001965	96.18	gold quality
right adrenal gland	UBERON:0001233	96.13	gold quality
upper leg skin	UBERON:0004262	96.06	gold quality
hypothalamus	UBERON:0001898	95.96	gold quality
entorhinal cortex	UBERON:0002728	95.90	gold quality
postcentral gyrus	UBERON:0002581	95.81	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	441.89
E-HCAD-5	yes	38.82
E-GEOD-93593	yes	16.51
E-MTAB-9388	yes	12.88
E-MTAB-7008	no	1475.41
E-ENAD-17	no	984.66
E-GEOD-124858	no	811.75
E-MTAB-6524	no	362.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

80 targeting PSAT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-579-3P	99.86	71.66	3628

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 38)

• nucleotide sequence and enzymatic activity of two isoforms generated by alternative splicing; differential expression depending upon tissue specificity and cellular proliferation status (PMID:12633500)
• Overexpression of phosphoserine aminotransferase is associated with colorectal cancer development (PMID:18221502)
• we propose an idea that PSAT1 may be implicated in altered serine metabolism and schizophrenia spectrum conditions. (PMID:20955740)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• PSAT1 expression positively correlates with the levels of phosphorylated cyclin D1 in non-small cell lung cancer. (PMID:25142862)
• phosphoserine aminotransferase deficiency is associated with Neu-Laxova syndrome. (PMID:25152457)
• High expression of PSAT is associated with Colon Cancer. (PMID:26439504)
• Data suggest that phosphoserine aminotransferase 1 (PSAT1) may be a promising anticancer therapeutic target. . (PMID:27372650)
• PSAT1 protein and mRNA levels were significantly associated to poor outcome to tamoxifen treatment of breast cancer. (PMID:28522855)
• PSAT1, which is overexpressed in ER-negative breast cancers, is activated by ATF4 and promotes cell cycle progression via regulation of the GSK3beta/beta-catenin/cyclin D1 pathway. (PMID:29216929)
• Nf1 loss promotes Kras-driven lung adenocarcinoma and results in Psat1-mediated glutamate dependence. (PMID:31036704)
• Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer. (PMID:31630284)
• This study is the first description of PHGDH and PSAT1 mutations in Chinese Neu-Laxova syndrome patients, which strongly implicates them in the pathogenesis of Neu-Laxova syndrome. (PMID:31903955)
• Overexpression of PSAT1 promotes metastasis of lung adenocarcinoma by suppressing the IRF1-IFNgamma axis. (PMID:31988456)
• A yeast-based complementation assay elucidates the functional impact of 200 missense variants in human PSAT1. (PMID:32077105)
• Overexpression of PSAT1 regulated by G9A sustains cell proliferation in colorectal cancer. (PMID:32300099)
• Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders. (PMID:32579715)
• PSAT1 Upregulation Contributes to Cell Growth and Cisplatin Resistance in Cervical Cancer Cells via Regulating PI3K/AKT Signaling Pathway. (PMID:32826249)
• Long noncoding RNA MEG3 suppresses epithelialtomesenchymal transition by inhibiting the PSAT1dependent GSK3beta/Snail signaling pathway in esophageal squamous cell carcinoma. (PMID:32901893)
• Serine Biosynthesis Is a Metabolic Vulnerability in IDH2-Driven Breast Cancer Progression. (PMID:33500247)
• Phosphoserine Aminotransferase has Conserved Active Site from Microbes to Higher Eukaryotes with Minor Deviations. (PMID:33588715)
• Adult diagnosis of congenital serine biosynthesis defect: A treatable cause of progressive neuropathy. (PMID:34089226)
• Lineage-specific silencing of PSAT1 induces serine auxotrophy and sensitivity to dietary serine starvation in luminal breast tumors. (PMID:35045283)
• Examination of the effects of microRNA-145-5p and phosphoserine aminotransferase 1 in colon cancer. (PMID:35615948)
• Circ_0015756 promotes ovarian cancer progression via the miR-145-5p/PSAT1 axis. (PMID:36327671)
• miRNA-195-5p/PSAT1 feedback loop in human triple-negative breast cancer cells. (PMID:36371491)
• Pathogenic PSAT1 Variants and Autosomal Recessive Axonal Charcot-Marie-Tooth Disease With Ichthyosis. (PMID:36599231)
• Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant. (PMID:36788227)
• L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. (PMID:36851825)
• Downregulation of PSAT1 inhibits cell proliferation and migration in uterine corpus endometrial carcinoma. (PMID:36906716)
• Exosomal ERBB2IP contributes to tumor growth via elevating PSAT1 expression in non-small cell lung carcinoma. (PMID:37192746)
• Phosphoserine Aminotransferase Pathogenetic Variants in Serine Deficiency Disorders: A Functional Characterization. (PMID:37627284)
• PSAT1 promotes autophagy to resist insufficient autophagy caused by cigarette smoke extract in human airway epithelial cells. (PMID:37832835)
• Overexpression of PSAT1 is Correlated with Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer. (PMID:37919070)
• Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma. (PMID:38373588)
• PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell. (PMID:39199378)
• PSAT1 is upregulated by METTL3 to attenuate high glucose-induced retinal pigment epithelial cell apoptosis and oxidative stress. (PMID:39407268)
• Interplay between acetylation and ubiquitination controls PSAT1 protein stability in lung adenocarcinoma. (PMID:39433916)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	psat1	ENSDARG00000016733
mus_musculus	Psat1	ENSMUSG00000024640
rattus_norvegicus	Psat1	ENSRNOG00000013971
drosophila_melanogaster	CG11899	FBGN0014427
caenorhabditis_elegans	F26H9.5	WBGENE00009177

Paralogs (1): AGXT (ENSG00000172482)

Protein

Protein identifiers

Phosphoserine aminotransferase — Q9Y617 (reviewed: Q9Y617)

Alternative names: Phosphohydroxythreonine aminotransferase

All UniProt accessions (1): Q9Y617

UniProt curated annotations — full annotation on UniProt →

Function. Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine. Catalyzes the second step, that is the pyridoxal 5’-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and alpha-ketoglutarate. Acts as an inhibitor of ferroptosis in response to interferon-gamma (IFNG) by promoting GPX4 stability: following phosphorylation by CAMK2A, PSAT1 interacts with GPX4 and provides 2-oxoglutarate to EGLN3, leading to GPX4 hydroxylation and stability.

Subunit / interactions. Homodimer.

Tissue specificity. Expressed at high levels in the brain, liver, kidney and pancreas, and very weakly expressed in the thymus, prostate, testis and colon.

Post-translational modifications. Phosphorylated at Ser-337 by CAMK2A in response to interferon-gamma (IFNG), promoting interaction with GPX4 and GPX4 hydroxylation by EGLN3.

Disease relevance. Phosphoserine aminotransferase deficiency (PSATD) [MIM:610992] Characterized biochemically by low plasma and cerebrospinal fluid concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphoserine transaminase activity is strongly stimulated by increasing the ionic strength.

Cofactor. Binds 2 pyridoxal phosphate molecules per dimer, each cofactor is bound at the monomer-monomer interface and forms contacts with residues from both chains.

Pathway. Amino-acid biosynthesis; L-serine biosynthesis; L-serine from 3-phospho-D-glycerate: step 2/3.

Similarity. Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. SerC subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y617-1	1, Alpha	yes
Q9Y617-2	2, Beta

RefSeq proteins (2): NP_066977, NP_478059* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000192	Aminotrans_V_dom	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR020578	Aminotrans_V_PyrdxlP_BS	Binding_site
IPR022278	Pser_aminoTfrase	Family

Pfam: PF00266

Enzyme classification (BRENDA):

• EC 2.6.1.4 — glycine transaminase (BRENDA: 8 organisms, 32 substrates, 23 inhibitors, 21 Km, 5 kcat entries)
• EC 2.6.1.52 — phosphoserine transaminase (BRENDA: 21 organisms, 28 substrates, 12 inhibitors, 57 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-GLUTAMATE	0.07–5.05	15
GLYOXYLATE	0.21–8.3	11
3-PHOSPHOHYDROXYPYRUVATE	0.005–5	8
3-PHOSPHOOXYPYRUVATE	0.0017–6	7
2-OXOGLUTARATE	0.043–0.8	6
O-PHOSPHO-L-SERINE	0.0118–0.225	6
GLUTAMATE	2–4.6	4
3-PHOSPHONOOXYPYRUVATE	0.01–0.1	4
L-GLUTAMATE	1.2–6.2	3
L-ALANINE	2.37–2.96	2
3-O-PHOSPHO-L-SERINE	0.017–0.037	2
4-(PHOSPHONOOXY)-L-THREONINE	0.11	2
L-HOMOSERINE	14.15–158.5	2
L-PHOSPHOSERINE	0.035–0.083	2
2-OXOGLUTARATE	0.55	1

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-serine + 2-oxoglutarate = 3-phosphooxypyruvate + L-glutamate (RHEA:14329)

UniProt features (78 total): helix 17, strand 15, binding site 13, sequence variant 11, modified residue 10, turn 7, mutagenesis site 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8A5V	X-RAY DIFFRACTION	2.46
3E77	X-RAY DIFFRACTION	2.5
8A5W	X-RAY DIFFRACTION	2.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y617-F1	97.09	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (13): 44 (in other chain); 242 (in other chain); 335; 336; 342; 45 (in other chain); 79; 80; 107; 156; 176; 199 …

Post-translational modifications (10): 1, 51, 127, 200, 269, 318, 323, 331, 333, 337

Mutagenesis-validated functional residues (2):

Position	Phenotype
200	abolished phosphoserine aminotransferase activity.
337	abolished phosphorylation by camk2a and ability to promote gpx4 hydroxylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-977347	Serine metabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 437 (showing top): GCM_MAP4K4, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_SERINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, LIU_VAV3_PROSTATE_CARCINOGENESIS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, GOBP_VITAMIN_BIOSYNTHETIC_PROCESS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13

GO Biological Process (5): L-serine biosynthetic process (GO:0006564), pyridoxine biosynthetic process (GO:0008615), negative regulation of ferroptosis (GO:0110076), L-serine metabolic process (GO:0006563), amino acid biosynthetic process (GO:0008652)

GO Molecular Function (6): O-phospho-L-serine:2-oxoglutarate transaminase activity (GO:0004648), pyridoxal phosphate binding (GO:0030170), identical protein binding (GO:0042802), protein binding (GO:0005515), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
L-serine metabolic process	1
serine family amino acid biosynthetic process	1
L-amino acid biosynthetic process	1
proteinogenic amino acid biosynthetic process	1
pyridoxine metabolic process	1
vitamin B6 biosynthetic process	1
negative regulation of programmed cell death	1
ferroptosis	1
regulation of ferroptosis	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
amino acid metabolic process	1
biosynthetic process	1
transaminase activity	1
anion binding	1
vitamin B6 binding	1
protein binding	1
binding	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

3190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSAT1	PSPH	P78330	919
PSAT1	PHGDH	O43175	893
PSAT1	SHMT2	P34897	815
PSAT1	SHMT1	P34896	794
PSAT1	ASNS	P08184	741
PSAT1	GLDC	P23378	687
PSAT1	MTHFD2	P13995	674
PSAT1	ALDH18A1	P54886	669
PSAT1	MTHFD1	P11586	669
PSAT1	MTHFD1L	Q6UB35	667
PSAT1	LDHA	P00338	622
PSAT1	TALDO1	P37837	610
PSAT1	SLC1A4	P43007	581
PSAT1	ASS1	P00966	580
PSAT1	P0DN79	P0DN79	572
PSAT1	BCAT1	P54687	572

IntAct

69 interactions, top by confidence:

A	B	Type	Score
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PSAT1	PSAT1	psi-mi:“MI:0915”(physical association)	0.560
CALR	PSAT1	psi-mi:“MI:0915”(physical association)	0.560
PSAT1	CDH1	psi-mi:“MI:0915”(physical association)	0.560
DLST	PSAT1	psi-mi:“MI:0915”(physical association)	0.560
PSAT1	NEK7	psi-mi:“MI:0915”(physical association)	0.560
PSMD10	PSAT1	psi-mi:“MI:0915”(physical association)	0.550
PTPRA	PTPRE	psi-mi:“MI:0914”(association)	0.420
PSAT1	MPRIP	psi-mi:“MI:0915”(physical association)	0.400
CEBPE	PSAT1	psi-mi:“MI:0915”(physical association)	0.370
PSAT1	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
SCARB2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PRKCE	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	BTAF1	psi-mi:“MI:0914”(association)	0.350
MAP3K7	ACOT7	psi-mi:“MI:0914”(association)	0.350
MYLK	ACOT7	psi-mi:“MI:0914”(association)	0.350

BioGRID (132): MPRIP (Affinity Capture-MS), CAB39 (Co-fractionation), HSPG2 (Co-fractionation), PCBP1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), PSAT1 (Co-fractionation), SGPL1 (Co-fractionation)

ESM2 similar proteins: A0A0C1E1D0, A7SCH8, B9DTW4, O42652, O74548, O85746, O94320, P00505, P00506, P00507, P00508, P04693, P05202, P08907, P09556, P10658, P12344, P12345, P23542, P26563, P28011, P28734, P37833, P44425, P46248, P46643, P46644, P46645, P46646, P52894, P72173, P74861, P91856, Q05567, Q10349, Q21890, Q22067, Q28F67, Q4R559, Q52RG7

Diamond homologs: A0LK14, A1A9I4, A1AWS0, A2RIS2, A3CPJ2, A3M7Z0, A4VU42, A4W0D4, A4XTE7, A5CWI0, A5FH28, A6GXC2, A6L5A6, A6T700, A6V2Q8, A6VZ92, A7MES8, A8FVN8, A8YW78, A9A0A5, A9B6Q3, B1HSU6, B2GBS2, B2HWW3, B5EPR5, B5FCJ8, B5XY88, B6YQL2, B7GY87, B7I5D6, B7J6V1, B7MHL6, B7MS22, B7NM68, B7V9J9, B8FLC3, B9DTW4, C1D8N3, C1DRQ9, C3K6J5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PSAT1	“up-regulates activity”	O-phosphonato-L-serine(2-)	“chemical modification”
“pyridoxal 5’-phosphate(2-)”	“up-regulates activity”	PSAT1	“chemical activation”
PSAT1	“up-regulates activity”	3-phosphonatooxypyruvate(3-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

530 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	10
Uncertain significance	144
Likely benign	143
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1081	NM_058179.4(PSAT1):c.107del (p.Gly36fs)	Pathogenic
1345889	NC_000009.11:g.(?80919631)(80923519_?)del	Pathogenic
1404307	NM_058179.4(PSAT1):c.664C>T (p.Arg222Ter)	Pathogenic
1455064	NM_058179.4(PSAT1):c.838G>T (p.Glu280Ter)	Pathogenic
1456971	NC_000009.11:g.(?80915498)(80916959_?)del	Pathogenic
1458396	NM_058179.4(PSAT1):c.444C>G (p.Tyr148Ter)	Pathogenic
156362	NM_058179.4(PSAT1):c.1023_1027delinsAGACCT (p.Arg342fs)	Pathogenic
156363	NM_058179.4(PSAT1):c.536C>T (p.Ser179Leu)	Pathogenic
2091002	NM_058179.4(PSAT1):c.892A>T (p.Arg298Ter)	Pathogenic
2097356	NM_058179.4(PSAT1):c.228del (p.Gly77fs)	Pathogenic
2119384	NM_058179.4(PSAT1):c.510_514del (p.Ala171fs)	Pathogenic
2427167	NC_000009.11:g.(?80921210)(80923519_?)del	Pathogenic
2581497	NM_058179.4(PSAT1):c.413del (p.Ser138fs)	Pathogenic
2700711	NM_058179.4(PSAT1):c.770G>A (p.Trp257Ter)	Pathogenic
2722660	NM_058179.4(PSAT1):c.357del (p.Thr120fs)	Pathogenic
2986158	NM_058179.4(PSAT1):c.76C>T (p.Gln26Ter)	Pathogenic
3245259	NC_000009.11:g.(?80912127)(80923519_?)del	Pathogenic
3641837	NM_058179.4(PSAT1):c.880G>T (p.Glu294Ter)	Pathogenic
3654866	NM_058179.4(PSAT1):c.598_605dup (p.Gly203fs)	Pathogenic
3674117	NM_058179.4(PSAT1):c.536C>G (p.Ser179Ter)	Pathogenic
372478	NM_058179.4(PSAT1):c.296_297delinsTG (p.Ala99Val)	Pathogenic
450376	NM_058179.4(PSAT1):c.432del (p.Asp145fs)	Pathogenic
578992	NM_058179.4(PSAT1):c.178del (p.Val60fs)	Pathogenic
654599	NM_058179.4(PSAT1):c.420G>A (p.Trp140Ter)	Pathogenic
1333513	NM_058179.4(PSAT1):c.444C>A (p.Tyr148Ter)	Likely pathogenic
1349393	NM_058179.4(PSAT1):c.570+2_570+15del	Likely pathogenic
1467660	NM_058179.4(PSAT1):c.976G>T (p.Glu326Ter)	Likely pathogenic
1501099	NM_058179.4(PSAT1):c.571-1G>A	Likely pathogenic
1502312	NM_058179.4(PSAT1):c.122-1G>C	Likely pathogenic
2140707	NM_058179.4(PSAT1):c.43_60+9del	Likely pathogenic

SpliceAI

1464 predictions. Top by Δscore:

Variant	Effect	Δscore
9:78297271:G:GG	donor_gain	1.0000
9:78301953:GAAAT:G	acceptor_gain	1.0000
9:78302021:GCT:G	donor_gain	1.0000
9:78302024:G:GG	donor_gain	1.0000
9:78308411:A:AG	acceptor_gain	1.0000
9:78308411:AAGTT:A	acceptor_loss	1.0000
9:78308412:A:G	acceptor_gain	1.0000
9:78308412:AGTTT:A	acceptor_gain	1.0000
9:78308413:G:GA	acceptor_gain	1.0000
9:78308413:GT:G	acceptor_gain	1.0000
9:78308413:GTT:G	acceptor_gain	1.0000
9:78308413:GTTT:G	acceptor_gain	1.0000
9:78308413:GTTTG:G	acceptor_gain	1.0000
9:78308580:TCAGG:T	donor_loss	1.0000
9:78308581:CAG:C	donor_loss	1.0000
9:78308582:AGGTA:A	donor_loss	1.0000
9:78308583:GGT:G	donor_loss	1.0000
9:78308584:G:GC	donor_loss	1.0000
9:78308585:T:A	donor_loss	1.0000
9:78317674:A:AG	acceptor_gain	1.0000
9:78317675:G:GG	acceptor_gain	1.0000
9:78317675:GC:G	acceptor_gain	1.0000
9:78317795:GATTC:G	donor_gain	1.0000
9:78317803:GT:G	donor_gain	1.0000
9:78317805:G:GG	donor_gain	1.0000
9:78328049:A:AG	acceptor_gain	1.0000
9:78328050:G:GG	acceptor_gain	1.0000
9:78297266:ACTCA:A	donor_gain	0.9900
9:78297267:CTCA:C	donor_gain	0.9900
9:78297268:TCA:T	donor_gain	0.9900

AlphaMissense

2433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:78304862:T:A	W107R	0.998
9:78304862:T:C	W107R	0.998
9:78306372:C:G	C152W	0.998
9:78306443:A:C	D176A	0.998
9:78306443:A:T	D176V	0.998
9:78306442:G:C	D176H	0.997
9:78308446:T:A	N201K	0.997
9:78308446:T:G	N201K	0.997
9:78301962:C:G	H44D	0.996
9:78304790:T:C	F83L	0.996
9:78304792:C:A	F83L	0.996
9:78304792:C:G	F83L	0.996
9:78304864:G:C	W107C	0.996
9:78304864:G:T	W107C	0.996
9:78306371:G:A	C152Y	0.996
9:78306378:T:A	N154K	0.996
9:78306378:T:G	N154K	0.996
9:78306380:A:T	E155V	0.996
9:78308440:G:C	Q199H	0.996
9:78308440:G:T	Q199H	0.996
9:78300653:A:C	S38R	0.995
9:78300655:T:A	S38R	0.995
9:78300655:T:G	S38R	0.995
9:78304857:G:A	G105E	0.995
9:78306392:G:T	G159V	0.995
9:78306442:G:T	D176Y	0.995
9:78306443:A:G	D176G	0.995
9:78328076:A:C	S299R	0.995
9:78328078:C:A	S299R	0.995
9:78328078:C:G	S299R	0.995

dbSNP variants (sampled 300 via entrez): RS1000129501 (9:78322854 A>G), RS1000161961 (9:78323176 A>C), RS1000349178 (9:78314233 G>A), RS1000484771 (9:78313911 T>A,C), RS1000591586 (9:78297735 G>A), RS1000610217 (9:78297585 T>A), RS1000650798 (9:78308472 T>A,C), RS1000686814 (9:78328959 C>A), RS1000713733 (9:78303127 C>G), RS1000746941 (9:78303390 A>G), RS1000779988 (9:78305260 G>A), RS1000840359 (9:78318527 G>C), RS1000917214 (9:78298679 A>AT), RS1000967359 (9:78323764 T>C), RS1001166873 (9:78321499 C>T)

Disease associations

OMIM: gene MIM:610936 | disease phenotypes: MIM:610992, MIM:616038

GenCC curated gene-disease

Disease	Classification	Inheritance
neurometabolic disorder due to serine deficiency	Definitive	Autosomal recessive
Neu-Laxova syndrome 2	Strong	Autosomal recessive
PSAT deficiency	Strong	Autosomal recessive
Neu-Laxova syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neurometabolic disorder due to serine deficiency	Definitive	AR

Mondo (5): PSAT deficiency (MONDO:0012596), Neu-Laxova syndrome 2 (MONDO:0014466), neurometabolic disorder due to serine deficiency (MONDO:0018162), microcephaly (MONDO:0001149), Neu-Laxova syndrome (MONDO:0000179)

Orphanet (4): Neu-Laxova syndrome (Orphanet:2671), Phosphoserine aminotransferase deficiency, infantile/juvenile form (Orphanet:284417), Neu-Laxova syndrome due to phosphoserine aminotransferase deficiency (Orphanet:583602), Neurometabolic disorder due to serine deficiency (Orphanet:35705)

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000457	Depressed nasal ridge
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000969	Edema
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001285	Spastic tetraparesis
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001336	Myoclonus
HP:0001339	Lissencephaly
HP:0001347	Hyperreflexia
HP:0001363	Craniosynostosis
HP:0001511	Intrauterine growth retardation
HP:0001522	Death in infancy
HP:0001531	Failure to thrive in infancy
HP:0001538	Protuberant abdomen
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001525_17	Visceral fat	4.000000e-06
GCST001762_417	Obesity-related traits	6.000000e-06
GCST009391_549	Metabolite levels	7.000000e-06
GCST011494_47	Daytime nap	1.000000e-43

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0010496	hippuric acid measurement
EFO:0007828	daytime rest measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C536405	Neu Laxova syndrome (supp.)
C567032	Phosphoserine Aminotransferase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066212 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.58	Kd	264	nM	CHEMBL5653589
6.58	ED50	264	nM	CHEMBL5653589
5.66	IC50	2200	nM	CHEMBL5611941

PubChem BioAssay actives

2 with measured affinity, of 3 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149098: Binding affinity to human PSAT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.2640	uM
2-aminooxy-3-(4-phenylphenyl)propanoic acid;hydrochloride	2126494: Inhibition of human PSAT extracted from Escherichia coli BL21(DE3) cells preincubated with compound followed by L-OPS addition in presence of PLP	ic50	2.2000	uM

CTD chemical–gene interactions

139 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases expression	7
bisphenol A	affects expression, increases expression, decreases expression	6
Estradiol	increases expression, increases reaction, affects cotreatment, decreases expression	6
sodium arsenite	affects expression, affects cotreatment, increases abundance, increases expression	5
Tretinoin	decreases expression	4
Cadmium Chloride	increases expression, affects expression, decreases expression, increases abundance	4
perfluorooctanoic acid	increases expression	3
perfluorooctane sulfonic acid	increases expression	3
Cisplatin	affects cotreatment, increases expression	3
Silicon Dioxide	affects secretion, decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Tunicamycin	increases expression	3
Valproic Acid	increases expression, increases methylation, decreases expression	3
tungsten carbide	affects cotreatment, decreases expression, increases expression	2
deoxynivalenol	decreases expression	2
didecyldimethylammonium	increases expression	2
bisphenol S	increases expression, increases methylation	2
Zoledronic Acid	decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Carbamazepine	affects expression	2
Cobalt	affects cotreatment, decreases expression, increases expression	2
Copper	affects binding, increases expression	2
Drugs, Chinese Herbal	increases expression	2
Oxygen	decreases expression	2
Progesterone	affects cotreatment, increases expression	2
Rotenone	decreases expression, increases expression	2
T-2 Toxin	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5610735	Binding	Inhibition of human PSAT extracted from Escherichia coli BL21(DE3) cells preincubated with compound followed by L-OPS addition in presence of PLP	Chemical Probes to Investigate Central Nervous System Disorders: Design, Synthesis and Mechanism of Action of a Potent Human Serine Racemase Inhibitor. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3F3	Abcam HEK293T PSAT1 KO	Transformed cell line	Female
CVCL_E4Q4	KOLF2.1J PSAT1 32.4kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_TH25	HAP1 PSAT1 (-) 1	Cancer cell line	Male
CVCL_XR94	HAP1 PSAT1 (-) 2	Cancer cell line	Male
CVCL_XR95	HAP1 PSAT1 (-) 3	Cancer cell line	Male
CVCL_XR96	HAP1 PSAT1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

18 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.