Neu-Laxova syndrome 2

Summary

Neu-Laxova syndrome 2 (MONDO:0014466) is a disease caused by PSAT1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PSAT1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 317

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Neu-Laxova syndrome 2
Mondo ID	MONDO:0014466
OMIM	616038
Orphanet	583602
DOID	DOID:0080075
UMLS	C4015019
MedGen	863456
GARD	0022335
Is cancer (heuristic)	no

Also known as: Neu-Laxova syndrome 2 · Neu-Laxova syndrome caused by mutation in PSAT1 · Neu-Laxova syndrome due to phosphoserine aminotransferase deficiency · Neu-Laxova syndrome type 2 · NLS2 · phosphoserine aminotransferase deficiency, prenatal form · PSAT1 Neu-Laxova syndrome

Data availability: 317 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 2

Related subtypes (2): Neu-Laxova syndrome 1, 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

317 retrieved; paginated sample, class counts are floors:

139 likely benign, 118 uncertain significance, 24 pathogenic, 14 conflicting classifications of pathogenicity, 10 benign, 7 likely pathogenic, 4 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1456972	NC_000009.11:g.(?79792621)(80944002_?)del	CEP78	Pathogenic	criteria provided, single submitter
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
1306418	NM_058179.4(PSAT1):c.870-1G>T	PSAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1345889	NC_000009.11:g.(?80919631)(80923519_?)del	PSAT1	Pathogenic	criteria provided, single submitter
1404307	NM_058179.4(PSAT1):c.664C>T (p.Arg222Ter)	PSAT1	Pathogenic	criteria provided, single submitter
1455064	NM_058179.4(PSAT1):c.838G>T (p.Glu280Ter)	PSAT1	Pathogenic	criteria provided, single submitter
1456971	NC_000009.11:g.(?80915498)(80916959_?)del	PSAT1	Pathogenic	criteria provided, single submitter
1458396	NM_058179.4(PSAT1):c.444C>G (p.Tyr148Ter)	PSAT1	Pathogenic	criteria provided, single submitter
156362	NM_058179.4(PSAT1):c.1023_1027delinsAGACCT (p.Arg342fs)	PSAT1	Pathogenic	no assertion criteria provided
156363	NM_058179.4(PSAT1):c.536C>T (p.Ser179Leu)	PSAT1	Pathogenic	criteria provided, single submitter
2061743	NM_058179.4(PSAT1):c.82_83del (p.Glu28fs)	PSAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2061942	NM_058179.4(PSAT1):c.949G>T (p.Glu317Ter)	PSAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2091002	NM_058179.4(PSAT1):c.892A>T (p.Arg298Ter)	PSAT1	Pathogenic	criteria provided, single submitter
2097356	NM_058179.4(PSAT1):c.228del (p.Gly77fs)	PSAT1	Pathogenic	criteria provided, single submitter
2119384	NM_058179.4(PSAT1):c.510_514del (p.Ala171fs)	PSAT1	Pathogenic	criteria provided, single submitter
2427167	NC_000009.11:g.(?80921210)(80923519_?)del	PSAT1	Pathogenic	criteria provided, single submitter
2581497	NM_058179.4(PSAT1):c.413del (p.Ser138fs)	PSAT1	Pathogenic	criteria provided, multiple submitters, no conflicts
2700711	NM_058179.4(PSAT1):c.770G>A (p.Trp257Ter)	PSAT1	Pathogenic	criteria provided, single submitter
2722660	NM_058179.4(PSAT1):c.357del (p.Thr120fs)	PSAT1	Pathogenic	criteria provided, single submitter
2986158	NM_058179.4(PSAT1):c.76C>T (p.Gln26Ter)	PSAT1	Pathogenic	criteria provided, single submitter
3245259	NC_000009.11:g.(?80912127)(80923519_?)del	PSAT1	Pathogenic	criteria provided, single submitter
3641837	NM_058179.4(PSAT1):c.880G>T (p.Glu294Ter)	PSAT1	Pathogenic	criteria provided, single submitter
3654866	NM_058179.4(PSAT1):c.598_605dup (p.Gly203fs)	PSAT1	Pathogenic	criteria provided, single submitter
3674117	NM_058179.4(PSAT1):c.536C>G (p.Ser179Ter)	PSAT1	Pathogenic	criteria provided, single submitter
372478	NM_058179.4(PSAT1):c.296_297delinsTG (p.Ala99Val)	PSAT1	Pathogenic	criteria provided, multiple submitters, no conflicts
578992	NM_058179.4(PSAT1):c.178del (p.Val60fs)	PSAT1	Pathogenic	criteria provided, single submitter
654599	NM_058179.4(PSAT1):c.420G>A (p.Trp140Ter)	PSAT1	Pathogenic	criteria provided, single submitter
1349393	NM_058179.4(PSAT1):c.570+2_570+15del	PSAT1	Likely pathogenic	criteria provided, single submitter
1467660	NM_058179.4(PSAT1):c.976G>T (p.Glu326Ter)	PSAT1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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

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
CEP78	Orphanet:231183	Usher syndrome type 3

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,clinvar
CEP78	HGNC:25740	ENSG00000148019	Q5JTW2	Centrosomal protein of 78 kDa	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.
CEP78	Centrosomal protein of 78 kDa	Centriole wall protein that localizes to mature centrioles and regulates centriole and cilia biogenesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

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
CEP78	Other/Unknown	no		Leu-rich_rpt, Cep78, LRR_dom_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
corpus epididymis	1
inferior vagus X ganglion	1
ventricular zone	1
buccal mucosa cell	1
oocyte	1
secondary oocyte	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
CEP78	239	ubiquitous	marker	secondary oocyte, oocyte, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSAT1	3,391
CEP78	1,373

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSAT1	Q9Y617	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEP78	Q5JTW2	64.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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	1	519.1×	0.029	PSAT1
Centrosome maturation	1	126.9×	0.029	CEP78
Loss of Nlp from mitotic centrosomes	1	79.3×	0.029	CEP78
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.029	CEP78
AURKA Activation by TPX2	1	76.1×	0.029	CEP78
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.029	CEP78
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.029	CEP78
Mitotic G2-G2/M phases	1	63.4×	0.029	CEP78
G2/M Transition	1	63.4×	0.029	CEP78
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.029	CEP78
Anchoring of the basal body to the plasma membrane	1	56.5×	0.029	CEP78
Cilium Assembly	1	54.4×	0.029	CEP78
Mitotic Prometaphase	1	34.6×	0.036	CEP78
Metabolism of amino acids and derivatives	1	33.8×	0.036	PSAT1
Organelle biogenesis and maintenance	1	33.0×	0.036	CEP78
M Phase	1	33.0×	0.036	CEP78
Cell Cycle, Mitotic	1	24.1×	0.046	CEP78
Cell Cycle	1	18.0×	0.058	CEP78
Metabolism	1	5.8×	0.165	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 2 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	4213.0×	0.002	PSAT1
L-serine biosynthetic process	1	2106.5×	0.002	PSAT1
negative regulation of ferroptosis	1	401.2×	0.005	PSAT1
protein localization to centrosome	1	337.0×	0.005	CEP78
cilium organization	1	300.9×	0.005	CEP78
protein localization to cilium	1	200.6×	0.007	CEP78
negative regulation of protein ubiquitination	1	142.8×	0.008	CEP78
flagellated sperm motility	1	58.5×	0.017	CEP78

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
CEP78	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: 2; 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	1	CEP78

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PSAT1	2	—
CEP78	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.