cutis laxa, autosomal recessive, type 2E

Summary

cutis laxa, autosomal recessive, type 2E (MONDO:0030337) is a disease caused by LTBP1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LTBP1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cutis laxa, autosomal recessive, type 2E
Mondo ID	MONDO:0030337
OMIM	619451
UMLS	C5561944
MedGen	1794154
GARD	0025543
Is cancer (heuristic)	no

Also known as: ARCL2E · cutis laxa, autosomal recessive, type 2E · cutis laxa, autosomal recessive, type IIE

Data availability: 12 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 › inherited cutis laxa › cutis laxa, autosomal recessive, type 2E

Related subtypes (13): craniofaciofrontodigital syndrome, arterial tortuosity syndrome, ALDH18A1-related de Barsy syndrome, autosomal recessive cutis laxa type 2, classic type, geroderma osteodysplastica, occipital horn syndrome, RIN2 syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, PYCR1-related de Barsy syndrome, autosomal dominant cutis laxa, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, arterial tortuosity-bone fragility syndrome

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

12 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 2 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184249	NM_206943.4(LTBP1):c.4844del (p.Asn1615fs)	LTBP1	Pathogenic	no assertion criteria provided
1184250	NM_206943.4(LTBP1):c.4431T>A (p.Cys1477Ter)	LTBP1	Pathogenic	no assertion criteria provided
1344546	NM_206943.4(LTBP1):c.3991dup (p.Thr1331fs)	LTBP1	Pathogenic	no assertion criteria provided
4278397	NM_206943.4(LTBP1):c.2168-1G>T	LTBP1	Pathogenic	criteria provided, single submitter
1184252	NM_206943.4(LTBP1):c.1342C>T (p.Gln448Ter)	LTBP1	Likely pathogenic	criteria provided, single submitter
1320250	NM_206943.4(LTBP1):c.4793_4794del (p.Glu1598fs)	LTBP1	Likely pathogenic	criteria provided, single submitter
4056587	NM_206943.4(LTBP1):c.22del (p.Trp8fs)	LOC129933461	Uncertain significance	criteria provided, single submitter
2366068	NM_206943.4(LTBP1):c.4538A>G (p.Asn1513Ser)	LTBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3391283	NM_206943.4(LTBP1):c.2959G>A (p.Gly987Arg)	LTBP1	Uncertain significance	criteria provided, single submitter
3766584	NM_206943.4(LTBP1):c.298CCG[6] (p.Pro106del)	LTBP1	Uncertain significance	criteria provided, single submitter
4277681	NM_206943.4(LTBP1):c.2698T>C (p.Cys900Arg)	LTBP1	Uncertain significance	criteria provided, single submitter
4814173	NM_206943.4(LTBP1):c.4367C>T (p.Thr1456Met)	LTBP1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
LTBP1	Strong	Autosomal recessive	cutis laxa, autosomal recessive, type 2E	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LTBP1	Orphanet:90349	Autosomal recessive cutis laxa type 1

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
LTBP1	HGNC:6714	ENSG00000049323	Q14766	Latent-transforming growth factor beta-binding protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LTBP1	Latent-transforming growth factor beta-binding protein 1	Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.

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)
LTBP1	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
blood vessel layer	1
descending thoracic aorta	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LTBP1	291	ubiquitous	marker	blood vessel layer, right coronary artery, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LTBP1	215

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LTBP1	Q14766	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Elastic fibre formation	1	335.9×	0.012	LTBP1
TGF-beta receptor signaling activates SMADs	1	326.3×	0.012	LTBP1
Molecules associated with elastic fibres	1	308.6×	0.012	LTBP1
Signaling by TGF-beta Receptor Complex	1	200.3×	0.014	LTBP1
Signaling by TGFB family members	1	115.3×	0.018	LTBP1
Post-translational protein phosphorylation	1	100.2×	0.018	LTBP1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.018	LTBP1
Extracellular matrix organization	1	63.1×	0.022	LTBP1
Post-translational protein modification	1	19.2×	0.064	LTBP1
Metabolism of proteins	1	12.4×	0.089	LTBP1
Signal Transduction	1	10.2×	0.098	LTBP1

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
establishment of protein localization to extracellular region	1	8426.0×	2e-04	LTBP1
obsolete sequestering of TGFbeta in extracellular matrix	1	4213.0×	2e-04	LTBP1

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
LTBP1	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	LTBP1

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)
LTBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.