Cutis laxa, autosomal recessive, type 1d

Summary

Cutis laxa, autosomal recessive, type 1d (MONDO:0958335) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cutis laxa, autosomal recessive, type 1d
Mondo ID	MONDO:0958335
OMIM	620780
UMLS	C5935602
MedGen	1857168
GARD	0027015
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 2 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 recessive disease › autosomal recessive cutis laxa type 1 › cutis laxa, autosomal recessive, type 1d

Related subtypes (2): cutis laxa, autosomal recessive, type 1A, cutis laxa, autosomal recessive, type 1B

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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1048805	NM_001039348.3(EFEMP1):c.1201C>T (p.Arg401Ter)	EFEMP1	Pathogenic	criteria provided, single submitter
691884	NM_001039348.3(EFEMP1):c.320_324del (p.Met107fs)	EFEMP1	Pathogenic	criteria provided, single submitter
691885	NM_001039348.3(EFEMP1):c.615T>A (p.Tyr205Ter)	EFEMP1	Pathogenic	criteria provided, single submitter
1042759	NM_001039348.3(EFEMP1):c.389T>C (p.Met130Thr)	EFEMP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
655652	NM_001039348.3(EFEMP1):c.163T>C (p.Cys55Arg)	EFEMP1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 2 · 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
EFEMP1	Strong	Autosomal recessive	autosomal recessive cutis laxa type 1	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EFEMP1	Orphanet:75376	Familial drusen
EFEMP1	Orphanet:98977	Juvenile glaucoma

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
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.

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)
EFEMP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

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
descending thoracic aorta	1
right coronary artery	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EFEMP1	286	ubiquitous	marker	right coronary artery, thoracic aorta, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EFEMP1	2,988

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EFEMP1	Q12805	77.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Molecules associated with elastic fibres	1	308.6×	0.003	EFEMP1

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
post-embryonic eye morphogenesis	1	5617.3×	0.001	EFEMP1
embryonic eye morphogenesis	1	1532.0×	0.003	EFEMP1
negative regulation of chondrocyte differentiation	1	674.1×	0.004	EFEMP1
peptidyl-tyrosine phosphorylation	1	421.3×	0.004	EFEMP1
camera-type eye development	1	358.6×	0.004	EFEMP1
epidermal growth factor receptor signaling pathway	1	247.8×	0.005	EFEMP1
visual perception	1	79.5×	0.014	EFEMP1
regulation of DNA-templated transcription	1	31.6×	0.032	EFEMP1

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
EFEMP1	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	EFEMP1

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)
EFEMP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.