PSAT deficiency

Summary

PSAT deficiency (MONDO:0012596) is a disease caused by PSAT1 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: PSAT1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 61
• Phenotypes (HPO): 40
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0001531	Failure to thrive in infancy	Very frequent (80-99%)
HP:0002154	Hyperglycinemia	Very frequent (80-99%)
HP:0008872	Feeding difficulties in infancy	Very frequent (80-99%)
HP:0011451	Congenital microcephaly	Very frequent (80-99%)
HP:0012279	Hyposerinemia	Very frequent (80-99%)
HP:0012736	Profound global developmental delay	Very frequent (80-99%)
HP:0030215	Inappropriate crying	Very frequent (80-99%)
HP:0000474	Thickened nuchal skin fold	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0008936	Axial hypotonia	Frequent (30-79%)
HP:0012430	Cerebral white matter hypoplasia	Frequent (30-79%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000340	Sloping forehead	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0001285	Spastic tetraparesis	Occasional (5-29%)
HP:0001320	Cerebellar vermis hypoplasia	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0001339	Lissencephaly	Occasional (5-29%)
HP:0001363	Craniosynostosis	Occasional (5-29%)
HP:0001776	Bilateral talipes equinovarus	Occasional (5-29%)
HP:0002392	EEG with polyspike wave complexes	Occasional (5-29%)
HP:0003121	Limb joint contracture	Occasional (5-29%)
HP:0005280	Depressed nasal bridge	Occasional (5-29%)
HP:0006380	Knee flexion contracture	Occasional (5-29%)
HP:0006466	Ankle flexion contracture	Occasional (5-29%)
HP:0006956	Dilation of lateral ventricles	Occasional (5-29%)
HP:0007704	Paroxysmal involuntary eye movements	Occasional (5-29%)
HP:0008064	Ichthyosis	Occasional (5-29%)
HP:0009879	Simplified gyral pattern	Occasional (5-29%)
HP:0011097	Epileptic spasm	Occasional (5-29%)
HP:0011196	EEG with focal sharp waves	Occasional (5-29%)
HP:0011471	Gastrostomy tube feeding in infancy	Occasional (5-29%)
HP:0012448	Delayed myelination	Occasional (5-29%)
HP:0040288	Nasogastric tube feeding	Occasional (5-29%)
HP:0200048	Cyanotic episode	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	PSAT deficiency
Mondo ID	MONDO:0012596
MeSH	C567032
OMIM	610992
Orphanet	284417
DOID	DOID:0050723
SNOMED CT	718603002
UMLS	C1970253
MedGen	410026
GARD	0013273
Is cancer (heuristic)	no

Also known as: phosphoserine aminotransferase deficiency · PSAT deficiency · PSATD

Data availability: 61 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn serine deficiency › neurometabolic disorder due to serine deficiency › PSAT deficiency

Related subtypes (4): PSPH deficiency, spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome, 3-phosphoglycerate dehydrogenase deficiency, serine biosynthesis pathway deficiency, infantile/juvenile form

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

61 retrieved; paginated sample, class counts are floors:

32 uncertain significance, 13 conflicting classifications of pathogenicity, 7 benign, 2 pathogenic, 2 pathogenic/likely pathogenic, 2 likely pathogenic, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1081	NM_058179.4(PSAT1):c.107del (p.Gly36fs)	PSAT1	Pathogenic	criteria provided, single submitter
1082	NM_058179.4(PSAT1):c.299A>C (p.Asp100Ala)	PSAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2061743	NM_058179.4(PSAT1):c.82_83del (p.Glu28fs)	PSAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
450376	NM_058179.4(PSAT1):c.432del (p.Asp145fs)	PSAT1	Pathogenic	criteria provided, single submitter
1333513	NM_058179.4(PSAT1):c.444C>A (p.Tyr148Ter)	PSAT1	Likely pathogenic	criteria provided, single submitter
977022	NM_058179.4(PSAT1):c.129T>G (p.Ser43Arg)	PSAT1	Likely pathogenic	criteria provided, single submitter
1409224	NM_058179.4(PSAT1):c.473A>G (p.His158Arg)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
156364	NM_058179.4(PSAT1):c.296C>T (p.Ala99Val)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367452	NM_058179.4(PSAT1):c.54G>A (p.Pro18=)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367456	NM_058179.4(PSAT1):c.398-14G>A	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367459	NM_058179.4(PSAT1):c.1007+13G>A	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
542039	NM_058179.4(PSAT1):c.916C>T (p.Arg306Cys)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
802488	NM_058179.4(PSAT1):c.121+5G>A	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
912649	NM_058179.4(PSAT1):c.1074C>T (p.Ala358=)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
913715	NM_058179.4(PSAT1):c.231A>T (p.Gly77=)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
913716	NM_058179.4(PSAT1):c.270C>T (p.Leu90=)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
914106	NM_058179.4(PSAT1):c.445G>A (p.Val149Met)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
914109	NM_058179.4(PSAT1):c.700G>T (p.Ala234Ser)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
976941	NM_058179.4(PSAT1):c.467C>T (p.Thr156Met)	PSAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
367451	NM_058179.4(PSAT1):c.43G>C (p.Ala15Pro)	PSAT1	Uncertain significance	criteria provided, single submitter
367453	NM_058179.4(PSAT1):c.55C>G (p.His19Asp)	PSAT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
367458	NM_058179.4(PSAT1):c.821A>C (p.Lys274Thr)	PSAT1	Uncertain significance	criteria provided, single submitter
367462	NM_058179.4(PSAT1):c.*241C>A	PSAT1	Uncertain significance	criteria provided, single submitter
367467	NM_058179.4(PSAT1):c.*670T>G	PSAT1	Uncertain significance	criteria provided, single submitter
367468	NM_058179.4(PSAT1):c.*789A>G	PSAT1	Uncertain significance	criteria provided, single submitter
450380	NM_058179.4(PSAT1):c.44C>T (p.Ala15Val)	PSAT1	Uncertain significance	criteria provided, single submitter
912614	NM_058179.4(PSAT1):c.4G>T (p.Asp2Tyr)	PSAT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
912615	NM_058179.4(PSAT1):c.10C>G (p.Pro4Ala)	PSAT1	Uncertain significance	criteria provided, single submitter
912616	NM_058179.4(PSAT1):c.104T>A (p.Val35Asp)	PSAT1	Uncertain significance	criteria provided, single submitter
912650	NM_058179.4(PSAT1):c.*219A>G	PSAT1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PSAT1	Strong	Autosomal recessive	PSAT deficiency	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PSAT1	Orphanet:284417	Phosphoserine aminotransferase deficiency, infantile/juvenile form
PSAT1	Orphanet:583602	Neu-Laxova syndrome due to phosphoserine aminotransferase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PSAT1	HGNC:19129	ENSG00000135069	Q9Y617	Phosphoserine aminotransferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PSAT1	Phosphoserine aminotransferase	Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PSAT1	Enzyme (other)	yes	2.6.1.4	Aminotrans_V_dom, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
inferior vagus X ganglion	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PSAT1	259	ubiquitous	marker	ventricular zone, inferior vagus X ganglion, corpus epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSAT1	3,391

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSAT1	Q9Y617	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Serine metabolism	1	1038.2×	0.003	PSAT1
Metabolism of amino acids and derivatives	1	67.6×	0.022	PSAT1
Metabolism	1	11.6×	0.086	PSAT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pyridoxine biosynthetic process	1	8426.0×	4e-04	PSAT1
L-serine biosynthetic process	1	4213.0×	4e-04	PSAT1
negative regulation of ferroptosis	1	802.5×	0.001	PSAT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PSAT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PSAT1	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PSAT1	2.6.1.4, 2.6.1.52	glycine transaminase, phosphoserine transaminase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PSAT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PSAT1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening