Tetraamelia syndrome 1

Summary

Tetraamelia syndrome 1 (MONDO:0060764) is a disease caused by WNT3 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: WNT3 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tetraamelia syndrome 1
Mondo ID	MONDO:0060764
OMIM	273395
DOID	DOID:0112192
UMLS	C4012268
MedGen	860705
GARD	0015238
Is cancer (heuristic)	no

Also known as: TETAMS1 · tetraamelia syndrome 1

Data availability: 1 ClinVar variant · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › tetraamelia-multiple malformations syndrome › tetraamelia syndrome 1

Related subtypes (1): tetraamelia syndrome 2

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 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13812	NM_030753.5(WNT3):c.247C>T (p.Gln83Ter)	LRRC37A2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
WNT3	Definitive	Autosomal recessive	tetraamelia syndrome 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT3	Orphanet:3301	Tetraamelia-multiple malformations syndrome

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
WNT3	HGNC:12782	ENSG00000108379	P56703	Proto-oncogene Wnt-3	gencc
LRRC37A2	HGNC:32404	ENSG00000238083	A6NM11	Leucine-rich repeat-containing protein 37A2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT3	Proto-oncogene Wnt-3	Ligand for members of the frizzled family of seven transmembrane receptors.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WNT3	Other/Unknown	no		Wnt, Wnt3, Wnt_CS
LRRC37A2	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC37

Expression context

Cohort genes with no expression data: 0.

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
hypothalamus	1
skin of abdomen	1
zone of skin	1
cerebellar hemisphere	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT3	129	broad	yes	skin of abdomen, zone of skin, hypothalamus
LRRC37A2	134		yes	right uterine tube, right testis, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WNT3	1,660
LRRC37A2	601

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WNT3	P56703	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRRC37A2	A6NM11	42.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
WNT ligand biogenesis and trafficking	1	423.0×	0.007	WNT3
Class B/2 (Secretin family receptors)	1	190.3×	0.008	WNT3
TCF dependent signaling in response to WNT	1	117.7×	0.008	WNT3

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
Spemann organizer formation at the anterior end of the primitive streak	1	16852.0×	0.002	WNT3
positive regulation of collateral sprouting in absence of injury	1	8426.0×	0.002	WNT3
regulation of mesenchymal stem cell differentiation	1	4213.0×	0.002	WNT3
head morphogenesis	1	2106.5×	0.002	WNT3
mammary gland epithelium development	1	1872.4×	0.002	WNT3
negative regulation of axon extension involved in axon guidance	1	1685.2×	0.002	WNT3
dorsal/ventral axis specification	1	1532.0×	0.002	WNT3
limb bud formation	1	1532.0×	0.002	WNT3
midbrain dopaminergic neuron differentiation	1	1203.7×	0.002	WNT3
gamete generation	1	887.0×	0.003	WNT3
anterior/posterior axis specification	1	732.7×	0.003	WNT3
embryonic hindlimb morphogenesis	1	581.1×	0.004	WNT3
mesoderm formation	1	495.6×	0.004	WNT3
embryonic forelimb morphogenesis	1	495.6×	0.004	WNT3
regulation of neurogenesis	1	401.2×	0.004	WNT3
positive regulation of Wnt signaling pathway	1	383.0×	0.004	WNT3
stem cell proliferation	1	312.1×	0.005	WNT3
cell fate commitment	1	295.6×	0.005	WNT3
cellular response to retinoic acid	1	234.1×	0.006	WNT3
positive regulation of osteoblast differentiation	1	224.7×	0.006	WNT3
cell morphogenesis	1	157.5×	0.008	WNT3
canonical Wnt signaling pathway	1	153.2×	0.008	WNT3
neuron differentiation	1	100.3×	0.011	WNT3
axon guidance	1	90.6×	0.012	WNT3
gene expression	1	79.9×	0.013	WNT3
positive regulation of gene expression	1	38.7×	0.026	WNT3

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
WNT3	0	0
LRRC37A2	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
WNT3	5	Functional:3, Binding:2

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	2	WNT3, LRRC37A2

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)
WNT3	5	—
LRRC37A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.