Cutis laxa, autosomal dominant 1

Summary

Cutis laxa, autosomal dominant 1 (MONDO:0007411) is a disease caused by ELN (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: ELN (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 129

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cutis laxa, autosomal dominant 1
Mondo ID	MONDO:0007411
OMIM	123700
DOID	DOID:0070130
UMLS	C3276539
MedGen	478169
GARD	0015055
Is cancer (heuristic)	no

Also known as: ADCL1 · autosomal dominant cutis laxa caused by mutation in ELN · cutis laxa, autosomal dominant · cutis laxa, autosomal dominant 1 · cutis laxa, autosomal dominant type 1 · ELN autosomal dominant cutis laxa

Data availability: 129 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant cutis laxa › cutis laxa, autosomal dominant 1

Related subtypes (2): cutis laxa, autosomal dominant 2, cutis laxa, autosomal dominant 3

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

129 retrieved; paginated sample, class counts are floors:

48 uncertain significance, 34 conflicting classifications of pathogenicity, 20 benign/likely benign, 11 benign, 7 pathogenic, 3 pathogenic/likely pathogenic, 3 likely pathogenic, 2 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1254893	NM_000501.4(ELN):c.800-1G>A	ELN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458249	NM_000501.4(ELN):c.166del (p.Leu56fs)	ELN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16723	NM_000501.4(ELN):c.1621C>T (p.Arg541Ter)	ELN	Pathogenic	criteria provided, multiple submitters, no conflicts
16726	NM_000501.4(ELN):c.1946del (p.Gly649fs)	ELN	Pathogenic	no assertion criteria provided
16728	NM_000501.4(ELN):c.1973del (p.Pro658fs)	ELN	Pathogenic	criteria provided, single submitter
16734	ELN, EX9-33DUP	ELN	Pathogenic	no assertion criteria provided
16735	ELN, 25-BP DEL, NT2114	ELN	Pathogenic	no assertion criteria provided
16736	ELN, 1-BP DEL, 2159C	ELN	Pathogenic	no assertion criteria provided
265121	NM_000501.4(ELN):c.2058del (p.Gly688fs)	ELN	Pathogenic	criteria provided, multiple submitters, no conflicts
835472	NM_000501.4(ELN):c.1149C>A (p.Tyr383Ter)	ELN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1678614	NM_000501.4(ELN):c.2151del (p.Ala718fs)	ELN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
202174	NM_000501.4(ELN):c.2161del (p.Arg721fs)	ELN	Likely pathogenic	no assertion criteria provided
3775199	NM_000501.4(ELN):c.1779del (p.Lys594fs)	ELN	Likely pathogenic	criteria provided, single submitter
1178166	NM_000501.4(ELN):c.1453_1488del (p.479VAPGVG[1])	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163391	NM_000501.4(ELN):c.1150+1G>A	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213166	NM_000501.4(ELN):c.1999C>T (p.Pro667Ser)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213171	NM_000501.4(ELN):c.326G>A (p.Gly109Asp)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213175	NM_000501.4(ELN):c.659C>T (p.Pro220Leu)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213192	NM_000501.4(ELN):c.647G>T (p.Gly216Val)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2632008	NM_000501.4(ELN):c.416G>A (p.Gly139Glu)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283421	NM_000501.4(ELN):c.470-10C>G	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360634	NM_000501.4(ELN):c.163+13A>G	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360636	NM_000501.4(ELN):c.328G>A (p.Ala110Thr)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360638	NM_000501.4(ELN):c.861G>A (p.Gly287=)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360649	NM_000501.4(ELN):c.1234G>A (p.Gly412Arg)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360651	NM_000501.4(ELN):c.1281C>T (p.Pro427=)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360658	NM_000501.4(ELN):c.1825C>T (p.Leu609Phe)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360659	NM_000501.4(ELN):c.1861G>A (p.Ala621Thr)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360660	NM_000501.4(ELN):c.1909G>A (p.Ala637Thr)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360661	NM_000501.4(ELN):c.2077C>T (p.Pro693Ser)	ELN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
ELN	Definitive	Autosomal dominant	cutis laxa, autosomal dominant 1	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELN	Orphanet:3193	Supravalvular aortic stenosis
ELN	Orphanet:90348	Autosomal dominant cutis laxa
ELN	Orphanet:904	Williams syndrome
ELN	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELN	HGNC:3327	ENSG00000049540	P15502	Elastin	gencc,clinvar
ELN-AS1	HGNC:40212	ENSG00000232415		ELN antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELN	Elastin	Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely.

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)
ELN	Other/Unknown	no		Tropoelastin
ELN-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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ascending aorta	2
descending thoracic aorta	2
thoracic aorta	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELN	227	broad	marker	descending thoracic aorta, ascending aorta, thoracic aorta
ELN-AS1	125	broad	marker	descending thoracic aorta, ascending aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ELN	2,692
ELN-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELN	P15502	36.20

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
Elastic fibre formation	1	335.9×	0.005	ELN
Molecules associated with elastic fibres	1	308.6×	0.005	ELN
Degradation of the extracellular matrix	1	117.7×	0.008	ELN

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
regulation of smooth muscle cell proliferation	1	1296.3×	0.003	ELN
extracellular matrix assembly	1	936.2×	0.003	ELN
stress fiber assembly	1	766.0×	0.003	ELN
respiratory gaseous exchange by respiratory system	1	624.1×	0.003	ELN
regulation of actin filament polymerization	1	581.1×	0.003	ELN
blood circulation	1	510.7×	0.003	ELN
aortic valve morphogenesis	1	432.1×	0.003	ELN
outflow tract morphogenesis	1	306.4×	0.004	ELN
skeletal muscle tissue development	1	290.6×	0.004	ELN
animal organ morphogenesis	1	191.5×	0.005	ELN

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
ELN	0	0
ELN-AS1	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	2	ELN, ELN-AS1

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)
ELN	0	—
ELN-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.