Neu-Laxova syndrome 1

Summary

Neu-Laxova syndrome 1 (MONDO:0009736) is a disease caused by PSPH (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PSPH (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 82

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Neu-Laxova syndrome 1
Mondo ID	MONDO:0009736
OMIM	256520
Orphanet	583607
DOID	DOID:0080076
UMLS	C4551478
MedGen	1633287
GARD	0022336
Is cancer (heuristic)	no

Also known as: 3-Phosphoglycerate dehydrogenase deficiency, neonatal form · 3-phosphoglycerate dehydrogenase deficiency, prenatal form · Neu-Laxova syndrome 1 · Neu-Laxova syndrome caused by mutation in PHGDH · Neu-Laxova syndrome due to 3-phosphoglycerate dehydrogenase deficiency · Neu-Laxova syndrome type 1 · NLS1 · PHGDH Neu-Laxova syndrome

Data availability: 82 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › Neu-Laxova syndrome › Neu-Laxova syndrome 1

Related subtypes (2): Neu-Laxova syndrome 2, neu-laxova syndrome due to 3-phosphoserine phosphatase deficiency

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

82 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 17 pathogenic/likely pathogenic, 9 conflicting classifications of pathogenicity, 9 likely pathogenic, 8 benign/likely benign, 7 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075323	NM_006623.4(PHGDH):c.1153C>T (p.Gln385Ter)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098314	NM_006623.4(PHGDH):c.357-1G>A	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1331415	NM_006623.4(PHGDH):c.2T>C (p.Met1Thr)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
139534	NM_006623.4(PHGDH):c.418G>A (p.Gly140Arg)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1406185	NM_006623.4(PHGDH):c.874C>T (p.Gln292Ter)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1414498	NM_006623.4(PHGDH):c.1A>G (p.Met1Val)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
156360	NM_006623.4(PHGDH):c.793G>A (p.Glu265Lys)	PHGDH	Pathogenic	no assertion criteria provided
2095806	NM_006623.4(PHGDH):c.1394del (p.Leu465fs)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2159326	NM_006623.4(PHGDH):c.1518G>A (p.Trp506Ter)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2169478	NM_006623.4(PHGDH):c.1A>C (p.Met1Leu)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2579118	NM_006623.4(PHGDH):c.765del (p.Ala257fs)	PHGDH	Pathogenic	criteria provided, single submitter
2783899	NM_006623.4(PHGDH):c.665_666dup (p.Ala223fs)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280721	NM_006623.4(PHGDH):c.290+2T>C	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2858025	NM_006623.4(PHGDH):c.992del (p.Pro331fs)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3867	NM_006623.4(PHGDH):c.1468G>A (p.Val490Met)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3870	NM_006623.4(PHGDH):c.403C>T (p.Arg135Trp)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3871	NM_006623.4(PHGDH):c.1129G>A (p.Gly377Ser)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522743	NM_006623.4(PHGDH):c.1030C>T (p.Arg344Ter)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
806198	NM_006623.4(PHGDH):c.901del (p.Val301fs)	PHGDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2038670	NM_006623.4(PHGDH):c.643+1G>A	PHGDH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3579588	NM_006623.4(PHGDH):c.78_91del (p.Leu28fs)	PHGDH	Likely pathogenic	criteria provided, single submitter
3579655	NM_006623.4(PHGDH):c.76_80delinsCTT (p.Gly26fs)	PHGDH	Likely pathogenic	criteria provided, single submitter
3579721	NM_006623.4(PHGDH):c.108dup (p.Ser37Ter)	PHGDH	Likely pathogenic	criteria provided, single submitter
3580376	NM_006623.4(PHGDH):c.737delinsCC (p.Leu246fs)	PHGDH	Likely pathogenic	criteria provided, single submitter
3580486	NM_006623.4(PHGDH):c.1078G>T (p.Gly360Ter)	PHGDH	Likely pathogenic	criteria provided, single submitter
836495	NM_006623.4(PHGDH):c.1078+1G>A	PHGDH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
916534	NM_006623.4(PHGDH):c.1286G>T (p.Gly429Val)	PHGDH	Likely pathogenic	criteria provided, single submitter
964779	NM_006623.4(PHGDH):c.412-1G>C	PHGDH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
139535	NM_006623.4(PHGDH):c.488G>A (p.Arg163Gln)	PHGDH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2548715	NM_006623.4(PHGDH):c.1210G>A (p.Val404Ile)	PHGDH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 4 · 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
PSPH	Definitive	Autosomal recessive	Neu-Laxova syndrome 1	7
PHGDH	Moderate	Autosomal recessive	Neu-Laxova syndrome 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHGDH	Orphanet:583607	Neu-Laxova syndrome due to 3-phosphoglycerate dehydrogenase deficiency
PHGDH	Orphanet:79351	3-phosphoglycerate dehydrogenase deficiency, infantile/juvenile form
PSPH	Orphanet:583612	Neu-Laxova syndrome due to 3-phosphoserine phosphatase deficiency
PSPH	Orphanet:79350	3-phosphoserine phosphatase deficiency, infantile/juvenile form

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PHGDH	HGNC:8923	ENSG00000092621	O43175	D-3-phosphoglycerate dehydrogenase	gencc,clinvar
PSPH	HGNC:9577	ENSG00000146733	P78330	Phosphoserine phosphatase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHGDH	D-3-phosphoglycerate dehydrogenase	Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway.
PSPH	Phosphoserine phosphatase	Catalyzes the last irreversible step in the biosynthesis of L-serine from carbohydrates, the dephosphorylation of O-phospho-L-serine to L-serine.

Protein-family classification

Druggable: 2 · 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)	2	12.0×	0.007

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PHGDH	Enzyme (other)	yes	1.1.1.95	D-isomer_2_OHA_DH_cat_dom, D-isomer_DH_NAD-bd, PGDH
PSPH	Enzyme (other)	yes	3.1.3.3	PSP, HAD_sf, HAD-like_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
ganglionic eminence	1
ventricular zone	1
adrenal tissue	1
right uterine tube	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHGDH	273	ubiquitous	marker	ventricular zone, ganglionic eminence, C1 segment of cervical spinal cord
PSPH	271	ubiquitous	marker	adrenal tissue, right uterine tube, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHGDH	6,320
PSPH	2,297

Intra-cohort edges

A	B	Sources
PHGDH	PSPH	biogrid_interaction, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHGDH	O43175	21
PSPH	P78330	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Serine metabolism	2	1038.2×	3e-06	PHGDH, PSPH
Metabolism of amino acids and derivatives	2	67.6×	3e-04	PHGDH, PSPH
Metabolism	2	11.6×	0.007	PHGDH, PSPH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
L-serine biosynthetic process	2	4213.0×	8e-07	PHGDH, PSPH
L-threonine metabolic process	1	8426.0×	0.001	PHGDH
obsolete GABA metabolic process	1	4213.0×	0.001	PHGDH
glial cell development	1	2808.7×	0.002	PHGDH
glycine metabolic process	1	1404.3×	0.002	PHGDH
taurine metabolic process	1	1404.3×	0.002	PHGDH
L-serine metabolic process	1	842.6×	0.003	PSPH
G1 to G0 transition	1	702.2×	0.003	PHGDH
L-glutamine metabolic process	1	648.1×	0.003	PHGDH
neural tube development	1	263.3×	0.006	PHGDH
spinal cord development	1	255.3×	0.006	PHGDH
response to testosterone	1	234.1×	0.006	PSPH
response to nutrient levels	1	183.2×	0.008	PSPH
response to mechanical stimulus	1	150.5×	0.009	PSPH
neuron projection development	1	61.1×	0.020	PHGDH
regulation of gene expression	1	41.7×	0.026	PHGDH
brain development	1	39.8×	0.026	PHGDH
in utero embryonic development	1	36.0×	0.028	PSPH

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PHGDH	DISULFIRAM

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PHGDH	1	4
PSPH	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DISULFIRAM	4	PHGDH

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PHGDH	118	Binding:118
PSPH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PHGDH	1.1.1.95	phosphoglycerate dehydrogenase
PSPH	3.1.3.3	phosphoserine phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PHGDH	118

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
DISULFIRAM	4	PHGDH

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PHGDH
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PSPH
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)
PSPH	1	PHGDH

Clinical trials & evidence

Clinical trials

Clinical trials: 0.