Lowry-Wood syndrome

Summary

Lowry-Wood syndrome (MONDO:0009191) is a disease with 3 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 20
• Phenotypes (HPO): 21
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0002656	Epiphyseal dysplasia	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0010582	Irregular epiphyses	Very frequent (80-99%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0002812	Coxa vara	Frequent (30-79%)
HP:0002829	Arthralgia	Frequent (30-79%)
HP:0007703	Abnormality of retinal pigmentation	Frequent (30-79%)
HP:0000483	Astigmatism	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000926	Platyspondyly	Occasional (5-29%)
HP:0001156	Brachydactyly	Occasional (5-29%)
HP:0001387	Joint stiffness	Occasional (5-29%)
HP:0002750	Delayed skeletal maturation	Occasional (5-29%)
HP:0002999	Patellar dislocation	Occasional (5-29%)
HP:0003042	Elbow dislocation	Occasional (5-29%)
HP:0003083	Dislocated radial head	Occasional (5-29%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0100643	Abnormality of nail color	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Lowry-Wood syndrome
Mondo ID	MONDO:0009191
MeSH	C537038
OMIM	226960
Orphanet	1824
ICD-11	1713071905
SNOMED CT	721975004
UMLS	C0796021
MedGen	162899
GARD	0000264
MedDRA	10062600
Is cancer (heuristic)	no

Also known as: epiphyseal dysplasia, microcephaly and nystagmus · epiphyseal dysplasia, multiple, with microcephaly and retinal dystrophy · epiphyseal dysplasia-microcephaly-nystagmus syndrome · Lowry Wood syndrome · Lowry-Wood syndrome · LWS

Data availability: 20 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › RNU4ATAC spectrum disorder › Lowry-Wood syndrome

Related subtypes (2): microcephalic osteodysplastic primordial dwarfism type I, Roifman syndrome

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

20 retrieved; paginated sample, class counts are floors:

6 pathogenic/likely pathogenic, 5 conflicting classifications of pathogenicity, 5 pathogenic, 2 uncertain significance, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
218082	NM_001395891.1(CLASP1):c.196-570C>T	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218083	NM_001395891.1(CLASP1):c.196-567G>A	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218085	NR_023343.3(RNU4ATAC):n.48G>A	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218087	NR_023343.3(RNU4ATAC):n.118T>C	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30178	NM_001395891.1(CLASP1):c.196-605C>T	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30179	NR_023343.3(RNU4ATAC):n.55G>A	CLASP1	Pathogenic	criteria provided, multiple submitters, no conflicts
30181	NC_000002.12:g.121530990G>A	CLASP1	Pathogenic	criteria provided, single submitter
30184	NR_023343.3(RNU4ATAC):n.50G>A	CLASP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
636959	NR_023343.3(RNU4ATAC):n.46G>A	CLASP1	Pathogenic	criteria provided, multiple submitters, no conflicts
977779	NR_023343.3(RNU4ATAC):n.120T>G	CLASP1	Pathogenic	no assertion criteria provided
977780	NR_023343.3(RNU4ATAC):n.114G>C	CLASP1	Pathogenic	no assertion criteria provided
692040	NM_001395891.1(CLASP1):c.196-562G>T	CLASP1	Likely pathogenic	criteria provided, single submitter
1403727	NM_001395891.1(CLASP1):c.196-571C>T	CLASP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1474999	NR_023343.3(RNU4ATAC):n.47T>G	CLASP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218084	NM_001395891.1(CLASP1):c.196-591C>T	CLASP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
692041	NM_001395891.1(CLASP1):c.196-607G>A	CLASP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
932367	NR_023343.3(RNU4ATAC):n.5A>C	CLASP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1478923	NR_023343.3(RNU4ATAC):n.66G>A	CLASP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1989614	NC_000002.12:g.121530980G>A	CLASP1-AS1	Uncertain significance	criteria provided, single submitter
1143919	NM_001395891.1(CLASP1):c.196-679dup	CLASP1	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
RNU4ATAC	Limited	Autosomal recessive	Lowry-Wood syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNU4ATAC	Orphanet:1824	Lowry-Wood syndrome
RNU4ATAC	Orphanet:2636	Microcephalic osteodysplastic primordial dwarfism types I and III
RNU4ATAC	Orphanet:353298	Roifman syndrome

Cohort genes → proteins

3 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNU4ATAC	HGNC:34016	ENSG00000264229		RNA, U4atac small nuclear	gencc
CLASP1	HGNC:17088	ENSG00000074054	Q7Z460	CLIP-associating protein 1	clinvar
CLASP1-AS1	HGNC:55328	ENSG00000265451		CLASP1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLASP1	CLIP-associating protein 1	Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNU4ATAC	Other/Unknown	no
CLASP1	Other/Unknown	no		ARM-like, ARM-type_fold, HEAT_type_2
CLASP1-AS1	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
primordial germ cell in gonad	2
sural nerve	1
cortical plate	1
dorsal motor nucleus of vagus nerve	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNU4ATAC	116	ubiquitous	marker	primordial germ cell in gonad, sural nerve, calcaneal tendon
CLASP1	286	ubiquitous	marker	cortical plate, calcaneal tendon, dorsal motor nucleus of vagus nerve
CLASP1-AS1	129		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLASP1	1,686
RNU4ATAC	0
CLASP1-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLASP1	Q7Z460	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 3 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
Role of ABL in ROBO-SLIT signaling	1	634.4×	0.024	CLASP1
Loss of Nlp from mitotic centrosomes	1	79.3×	0.026	CLASP1
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.026	CLASP1
RNA polymerase II transcribes snRNA genes	1	77.2×	0.026	RNU4ATAC
AURKA Activation by TPX2	1	76.1×	0.026	CLASP1
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.026	CLASP1
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.026	CLASP1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	58.3×	0.026	CLASP1
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.026	CLASP1
Anchoring of the basal body to the plasma membrane	1	56.5×	0.026	CLASP1
EML4 and NUDC in mitotic spindle formation	1	46.4×	0.029	CLASP1
Resolution of Sister Chromatid Cohesion	1	43.3×	0.029	CLASP1
RHO GTPases Activate Formins	1	38.8×	0.030	CLASP1
Mitotic Prometaphase	1	34.6×	0.031	CLASP1
Separation of Sister Chromatids	1	30.4×	0.033	CLASP1

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
negative regulation of microtubule polymerization or depolymerization	1	5617.3×	0.002	CLASP1
establishment of mitotic spindle localization	1	2808.7×	0.002	CLASP1
negative regulation of wound healing, spreading of epidermal cells	1	2407.4×	0.002	CLASP1
establishment of spindle orientation	1	2106.5×	0.002	CLASP1
obsolete vesicle targeting	1	1685.2×	0.002	CLASP1
microtubule organizing center organization	1	1404.3×	0.002	CLASP1
astral microtubule organization	1	1296.3×	0.002	CLASP1
microtubule anchoring	1	1296.3×	0.002	CLASP1
positive regulation of extracellular matrix disassembly	1	1203.7×	0.002	CLASP1
exit from mitosis	1	1053.2×	0.002	CLASP1
positive regulation of microtubule polymerization	1	674.1×	0.003	CLASP1
microtubule nucleation	1	624.1×	0.003	CLASP1
positive regulation of exocytosis	1	601.9×	0.003	CLASP1
regulation of focal adhesion assembly	1	601.9×	0.003	CLASP1
negative regulation of stress fiber assembly	1	581.1×	0.003	CLASP1
microtubule bundle formation	1	510.7×	0.003	CLASP1
basement membrane organization	1	510.7×	0.003	CLASP1
negative regulation of microtubule depolymerization	1	495.6×	0.003	CLASP1
positive regulation of epithelial cell migration	1	411.0×	0.003	CLASP1
establishment or maintenance of cell polarity	1	401.2×	0.003	CLASP1
mitotic spindle assembly	1	343.9×	0.003	CLASP1
mitotic spindle organization	1	271.8×	0.004	CLASP1
Golgi organization	1	133.8×	0.008	CLASP1
microtubule cytoskeleton organization	1	121.2×	0.009	CLASP1
cell division	1	46.2×	0.022	CLASP1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RNU4ATAC	0	0
CLASP1	0	0
CLASP1-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CLASP1	10	Binding:10

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	RNU4ATAC, CLASP1, CLASP1-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RNU4ATAC	0	—
CLASP1	10	—
CLASP1-AS1	0	—

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
NCT06111950	Not specified	RECRUITING	Study of the Pathophysiology of RNU4ATAC and RTTN Associated Syndromes