Auriculocondylar syndrome 3

Summary

Auriculocondylar syndrome 3 (MONDO:0014312) is a disease caused by EDN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EDN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	auriculocondylar syndrome 3
Mondo ID	MONDO:0014312
OMIM	615706
UMLS	C3810332
MedGen	816662
GARD	0016003
Is cancer (heuristic)	no

Also known as: ARCND3 · Auriculocondylar syndrome 3 · Auriculocondylar syndrome type 3

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ear malformation › auriculocondylar syndrome › auriculocondylar syndrome 3

Related subtypes (5): auriculocondylar syndrome 1, question mark ears, isolated, auriculocondylar syndrome 2, auriculocondylar syndrome 4, auriculocondylar syndrome 2B

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

6 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 benign, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
120212	NM_001955.5(EDN1):c.271A>G (p.Lys91Glu)	EDN1	Pathogenic	no assertion criteria provided
120213	NM_001955.5(EDN1):c.230C>A (p.Pro77His)	EDN1	Pathogenic	no assertion criteria provided
3087196	NM_001955.5(EDN1):c.89C>T (p.Ala30Val)	EDN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892140	NM_001955.5(EDN1):c.501AAG[1] (p.Arg168del)	EDN1	Uncertain significance	criteria provided, single submitter
1255370	NM_001955.5(EDN1):c.318A>G (p.Glu106=)	EDN1	Benign	criteria provided, multiple submitters, no conflicts
16652	NM_001955.5(EDN1):c.594G>T (p.Lys198Asn)	EDN1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
EDN1	Strong	Autosomal recessive	auriculocondylar syndrome 3	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EDN1	Orphanet:137888	Auriculocondylar 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
EDN1	HGNC:3176	ENSG00000078401	P05305	Endothelin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EDN1	Endothelin-1	Endothelins are endothelium-derived vasoconstrictor peptides.

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)
EDN1	Other/Unknown	no		Endothln-like_toxin, Endothelin_toxin_CS, Endothelin

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
buccal mucosa cell	1
lower lobe of lung	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EDN1	253	ubiquitous	marker	lower lobe of lung, buccal mucosa cell, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EDN1	3,756

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EDN1	P05305	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.017	EDN1
Peptide ligand-binding receptors	1	74.2×	0.017	EDN1
G alpha (q) signalling events	1	57.4×	0.017	EDN1

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
rhythmic excitation	1	16852.0×	0.001	EDN1
histamine secretion	1	8426.0×	0.001	EDN1
phospholipase D-activating G protein-coupled receptor signaling pathway	1	8426.0×	0.001	EDN1
cellular response to human chorionic gonadotropin stimulus	1	8426.0×	0.001	EDN1
positive regulation of chemokine-mediated signaling pathway	1	8426.0×	0.001	EDN1
response to prostaglandin F	1	5617.3×	0.001	EDN1
cellular response to mineralocorticoid stimulus	1	5617.3×	0.001	EDN1
endothelin receptor signaling pathway involved in heart process	1	5617.3×	0.001	EDN1
negative regulation of phospholipase C/protein kinase C signal transduction	1	5617.3×	0.001	EDN1
semaphorin-plexin signaling pathway involved in axon guidance	1	5617.3×	0.001	EDN1
neural crest cell fate commitment	1	4213.0×	0.001	EDN1
vein smooth muscle contraction	1	4213.0×	0.001	EDN1
positive regulation of renal sodium excretion	1	4213.0×	0.001	EDN1
positive regulation of cell growth involved in cardiac muscle cell development	1	4213.0×	0.001	EDN1
sympathetic neuron axon guidance	1	4213.0×	0.001	EDN1
positive regulation of cation channel activity	1	4213.0×	0.001	EDN1
response to ozone	1	3370.4×	0.001	EDN1
nitric oxide transport	1	3370.4×	0.001	EDN1
positive regulation of odontogenesis	1	3370.4×	0.001	EDN1
leukocyte activation	1	3370.4×	0.001	EDN1
maternal process involved in parturition	1	3370.4×	0.001	EDN1
glomerular endothelium development	1	3370.4×	0.001	EDN1
renal albumin absorption	1	3370.4×	0.001	EDN1
positive regulation of artery morphogenesis	1	3370.4×	0.001	EDN1
regulation of systemic arterial blood pressure by endothelin	1	2808.7×	0.001	EDN1
peptide hormone secretion	1	2808.7×	0.001	EDN1
heparin proteoglycan metabolic process	1	2808.7×	0.001	EDN1
positive regulation of sarcomere organization	1	2808.7×	0.001	EDN1
cellular response to luteinizing hormone stimulus	1	2808.7×	0.001	EDN1
meiotic cell cycle process involved in oocyte maturation	1	2808.7×	0.001	EDN1

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
EDN1	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	EDN1

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)
EDN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.