Neu-Laxova syndrome

Summary

Neu-Laxova syndrome (MONDO:0000179) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 63

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		91	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

63 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000340	Sloping forehead	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0008064	Ichthyosis	Very frequent (80-99%)
HP:0012471	Thick vermilion border	Very frequent (80-99%)
HP:0012639	Abnormal nervous system morphology	Very frequent (80-99%)
HP:0100679	Lack of skin elasticity	Very frequent (80-99%)
HP:0001302	Pachygyria	Frequent (30-79%)
HP:0000062	Ambiguous genitalia	Frequent (30-79%)
HP:0000135	Hypogonadism	Frequent (30-79%)
HP:0000153	Abnormality of the mouth	Frequent (30-79%)
HP:0000211	Trismus	Frequent (30-79%)
HP:0000232	Everted lower lip vermilion	Frequent (30-79%)
HP:0000288	Abnormality of the philtrum	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000400	Macrotia	Frequent (30-79%)
HP:0000457	Depressed nasal ridge	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0000951	Abnormality of the skin	Frequent (30-79%)
HP:0001176	Large hands	Frequent (30-79%)
HP:0001305	Dandy-Walker malformation	Frequent (30-79%)
HP:0001321	Cerebellar hypoplasia	Frequent (30-79%)
HP:0001331	Absent septum pellucidum	Frequent (30-79%)
HP:0001339	Lissencephaly	Frequent (30-79%)
HP:0001371	Flexion contracture	Frequent (30-79%)
HP:0001460	Aplasia/Hypoplasia involving the skeletal musculature	Frequent (30-79%)
HP:0001558	Decreased fetal movement	Frequent (30-79%)
HP:0001561	Polyhydramnios	Frequent (30-79%)
HP:0001769	Broad foot	Frequent (30-79%)
HP:0002126	Polymicrogyria	Frequent (30-79%)
HP:0002179	Opisthotonus	Frequent (30-79%)
HP:0002269	Abnormality of neuronal migration	Frequent (30-79%)
HP:0002334	Abnormality of the cerebellar vermis	Frequent (30-79%)
HP:0002536	Abnormal cortical gyration	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)
HP:0003241	External genital hypoplasia	Frequent (30-79%)
HP:0003394	Muscle spasm	Frequent (30-79%)
HP:0003560	Muscular dystrophy	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000176	Submucous cleft hard palate	Occasional (5-29%)
HP:0000193	Bifid uvula	Occasional (5-29%)
HP:0000269	Prominent occiput	Occasional (5-29%)
HP:0000278	Retrognathia	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000492	Abnormal eyelid morphology	Occasional (5-29%)
HP:0000499	Abnormal eyelash morphology	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000614	Abnormal nasolacrimal system morphology	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Neu-Laxova syndrome
Mondo ID	MONDO:0000179
MeSH	C536405
OMIM	256520
Orphanet	2671
ICD-11	893358230
SNOMED CT	77817004
UMLS	C0265218
MedGen	78537
GARD	0000102
Is cancer (heuristic)	no

Also known as: Neu Laxova syndrome · NLS

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (35): cutaneous mycosis, integumentary system benign neoplasm, integumentary system cancer, nipple neoplasm, nail disorder, disorder of pilosebaceous unit, Bartholin duct cyst, benign mammary dysplasia, skin disorder, breast fibrosis, breast mucosa-associated lymphoid tissue lymphoma, panniculitis, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, autosomal dominant deafness - onychodystrophy syndrome, keratoderma hereditarium mutilans, Rombo syndrome, Sjogren-Larsson syndrome, mucosulfatidosis, ichthyosis prematurity syndrome, ANE syndrome, frontonasal dysplasia with alopecia and genital anomaly, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, cutis laxa, X-linked ichthyosis syndrome, demodicidosis, Proteus-like syndrome, familial atypical multiple mole melanoma syndrome, familial tumoral calcinosis, subcutaneous tissue disorder, Bartholin gland neoplasm, pseudoxanthoma elasticum (inherited or acquired), skin appendage disorder, keratinization disease, paraneoplastic cutaneous syndrome

Subtypes (3): Neu-Laxova syndrome 1, 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

No tiered GWAS variants or ClinVar records for this disease.

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
PSAT1	Strong	Autosomal recessive	Neu-Laxova syndrome 2	7
PHGDH	Moderate	Autosomal recessive	Neu-Laxova syndrome 1	6

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
PHGDH	Orphanet:583607	Neu-Laxova syndrome due to 3-phosphoglycerate dehydrogenase deficiency
PHGDH	Orphanet:79351	3-phosphoglycerate dehydrogenase 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
PSAT1	HGNC:19129	ENSG00000135069	Q9Y617	Phosphoserine aminotransferase	gencc
PHGDH	HGNC:8923	ENSG00000092621	O43175	D-3-phosphoglycerate dehydrogenase	gencc

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.
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.

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)
PSAT1	Enzyme (other)	yes	2.6.1.4	Aminotrans_V_dom, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
PHGDH	Enzyme (other)	yes	1.1.1.95	D-isomer_2_OHA_DH_cat_dom, D-isomer_DH_NAD-bd, PGDH

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
ventricular zone	2
corpus epididymis	1
inferior vagus X ganglion	1
C1 segment of cervical spinal cord	1
ganglionic eminence	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
PHGDH	273	ubiquitous	marker	ventricular zone, ganglionic eminence, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHGDH	6,320
PSAT1	3,391

Intra-cohort edges

A	B	Sources
PHGDH	PSAT1	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
PSAT1	Q9Y617	3

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	PSAT1, PHGDH
Metabolism of amino acids and derivatives	2	67.6×	3e-04	PSAT1, PHGDH
Metabolism	2	11.6×	0.007	PSAT1, PHGDH

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×	6e-07	PSAT1, PHGDH
L-threonine metabolic process	1	8426.0×	9e-04	PHGDH
pyridoxine biosynthetic process	1	4213.0×	9e-04	PSAT1
obsolete GABA metabolic process	1	4213.0×	9e-04	PHGDH
glial cell development	1	2808.7×	0.001	PHGDH
glycine metabolic process	1	1404.3×	0.002	PHGDH
taurine metabolic process	1	1404.3×	0.002	PHGDH
G1 to G0 transition	1	702.2×	0.003	PHGDH
L-glutamine metabolic process	1	648.1×	0.003	PHGDH
negative regulation of ferroptosis	1	401.2×	0.004	PSAT1
neural tube development	1	263.3×	0.005	PHGDH
spinal cord development	1	255.3×	0.005	PHGDH
neuron projection development	1	61.1×	0.019	PHGDH
regulation of gene expression	1	41.7×	0.025	PHGDH
brain development	1	39.8×	0.025	PHGDH

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
PSAT1	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
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
PHGDH	1.1.1.95	phosphoglycerate dehydrogenase

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	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	PHGDH

Clinical trials & evidence

Clinical trials

Clinical trials: 0.