ENDOVE syndrome, limb-only type

Summary

ENDOVE syndrome, limb-only type (MONDO:0030978) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ENDOVE syndrome, limb-only type
Mondo ID	MONDO:0030978
OMIM	619217
UMLS	C5543128
MedGen	1787128
GARD	0018560
Is cancer (heuristic)	no

Also known as: ENDOVESL · Mesomelia of Lower Extremities With Hand and Foot Anomalies

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

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › EN1-related dorsoventral syndrome › ENDOVE syndrome, limb-only type

Related subtypes (1): ENDOVE syndrome, limb-brain type

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
3252043	NC_000002.12:g.118561492_118589320del		Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
EN1	Limited	Unknown	ENDOVE syndrome, limb-only type	2

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
EN1	HGNC:3342	ENSG00000163064	Q05925	Homeobox protein engrailed-1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EN1	Homeobox protein engrailed-1	Required for proper formation of the apical ectodermal ridge and correct dorsal-ventral patterning in the limb.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EN1	Transcription factor	no		HD_engrailed, HD, Homeodomain-like_sf

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
skin of leg	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EN1	85	broad	yes	substantia nigra pars reticulata, skin of leg, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EN1	1,276

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EN1	Q05925	58.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
midbrain-hindbrain boundary development	1	8426.0×	0.003	EN1
motor learning	1	2407.4×	0.004	EN1
drinking behavior	1	991.3×	0.004	EN1
embryonic brain development	1	802.5×	0.004	EN1
pigmentation	1	702.2×	0.004	EN1
proximal/distal pattern formation	1	648.1×	0.004	EN1
dopaminergic neuron differentiation	1	624.1×	0.004	EN1
central nervous system neuron differentiation	1	601.9×	0.004	EN1
midbrain development	1	601.9×	0.004	EN1
response to cocaine	1	581.1×	0.004	EN1
embryonic forelimb morphogenesis	1	495.6×	0.004	EN1
dorsal/ventral pattern formation	1	421.3×	0.005	EN1
cerebellum development	1	358.6×	0.005	EN1
adult locomotory behavior	1	300.9×	0.006	EN1
social behavior	1	271.8×	0.006	EN1
neuron development	1	255.3×	0.006	EN1
anatomical structure morphogenesis	1	139.3×	0.010	EN1
multicellular organism growth	1	137.0×	0.010	EN1
skeletal system development	1	125.8×	0.010	EN1
negative regulation of neuron apoptotic process	1	110.9×	0.011	EN1
neuron differentiation	1	100.3×	0.011	EN1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.062	EN1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.070	EN1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	EN1

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
EN1	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	EN1

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)
EN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.