Caudal regression sequence

Summary

Caudal regression sequence (MONDO:0017607) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 29
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.75	Australia	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0002607	Bowel incontinence	Very frequent (80-99%)
HP:0002644	Abnormality of pelvic girdle bone morphology	Very frequent (80-99%)
HP:0003199	Decreased muscle mass	Very frequent (80-99%)
HP:0005640	Abnormal vertebral segmentation and fusion	Very frequent (80-99%)
HP:0008479	Hypoplastic vertebral bodies	Very frequent (80-99%)
HP:0008517	Aplasia/Hypoplasia of the sacrum	Very frequent (80-99%)
HP:0009800	Maternal diabetes	Very frequent (80-99%)
HP:0011867	Abnormality of the wing of the ilium	Very frequent (80-99%)
HP:0100710	Impulsivity	Very frequent (80-99%)
HP:0000069	Abnormality of the ureter	Frequent (30-79%)
HP:0000073	Ureteral duplication	Frequent (30-79%)
HP:0000076	Vesicoureteral reflux	Frequent (30-79%)
HP:0000086	Ectopic kidney	Frequent (30-79%)
HP:0000104	Renal agenesis	Frequent (30-79%)
HP:0001315	Reduced tendon reflexes	Frequent (30-79%)
HP:0001387	Joint stiffness	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0002023	Anal atresia	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000062	Ambiguous genitalia	Occasional (5-29%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0000921	Missing ribs	Occasional (5-29%)
HP:0002089	Pulmonary hypoplasia	Occasional (5-29%)
HP:0002139	Arrhinencephaly	Occasional (5-29%)
HP:0002308	Chiari malformation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	caudal regression sequence
Mondo ID	MONDO:0017607
Orphanet	3027
DOID	DOID:0080700
ICD-11	269997265
NCIT	C124505
UMLS	C0300948
MedGen	81254
GARD	0006007
MedDRA	10054842, 10059387, 10068896
NORD	902
Is cancer (heuristic)	no

Also known as: caudal dysplasia · Caudal Regression Syndrome · sacral agenesis syndrome · sacral regression syndrome

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system malformation › neural tube defect › caudal regression sequence

Related subtypes (11): Chiari malformation type I, lateral meningocele syndrome, diastematomyelia, lipomyelomeningocele, sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome, leptomyelolipoma, primary tethered cord syndrome, neurenteric cyst, isolated amyelia, parietal foramina, iniencephaly

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1346	NM_138959.3(VANGL1):c.715G>A (p.Val239Ile)	VANGL1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VANGL1	Orphanet:3027	Caudal regression syndrome

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
VANGL1	HGNC:15512	ENSG00000173218	Q8TAA9	Vang-like protein 1	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VANGL1	Other/Unknown	no		VANGL

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
bronchial epithelial cell	1
caput epididymis	1
corpus epididymis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VANGL1	234	ubiquitous	marker	bronchial epithelial cell, corpus epididymis, caput epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VANGL1	1,864

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VANGL1	Q8TAA9	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
RHOH GTPase cycle	1	308.6×	0.009	VANGL1
RHOV GTPase cycle	1	285.5×	0.009	VANGL1
RHOU GTPase cycle	1	278.5×	0.009	VANGL1
RND1 GTPase cycle	1	265.6×	0.009	VANGL1
RHOF GTPase cycle	1	259.6×	0.009	VANGL1
RND3 GTPase cycle	1	259.6×	0.009	VANGL1
RND2 GTPase cycle	1	259.6×	0.009	VANGL1
RHOD GTPase cycle	1	203.9×	0.009	VANGL1
RHOJ GTPase cycle	1	200.3×	0.009	VANGL1
RHOQ GTPase cycle	1	181.3×	0.009	VANGL1
RHOB GTPase cycle	1	154.3×	0.009	VANGL1
RHOG GTPase cycle	1	148.3×	0.009	VANGL1
RHOC GTPase cycle	1	146.4×	0.009	VANGL1
RAC2 GTPase cycle	1	126.9×	0.010	VANGL1
RAC3 GTPase cycle	1	119.0×	0.010	VANGL1
RHOA GTPase cycle	1	74.6×	0.015	VANGL1
CDC42 GTPase cycle	1	72.3×	0.015	VANGL1
RAC1 GTPase cycle	1	61.1×	0.016	VANGL1

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
mucociliary clearance	1	1296.3×	0.002	VANGL1
pigmentation	1	702.2×	0.002	VANGL1
Wnt signaling pathway, planar cell polarity pathway	1	455.5×	0.002	VANGL1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VANGL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	VANGL1

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)
VANGL1	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
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford