Cutis laxa

disease

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Also known as elastolysisgeneralised elastolysisgeneralized elastolysis

Summary

Cutis laxa (MONDO:0016175) is a disease with 12 cohort genes and 6 clinical trials. The dominant Reactome pathway is Molecules associated with elastic fibres (4 cohort genes).

At a glance

Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
Cohort genes: 12
ClinVar variants: 124
Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.1	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	cutis laxa
Mondo ID	MONDO:0016175
MeSH	D003483
Orphanet	209
DOID	DOID:3144
ICD-11	1227401566
NCIT	C84663
SNOMED CT	58588007
UMLS	C0010495
MedGen	8206
GARD	0006227
MedDRA	10011692
NORD	1022
Is cancer (heuristic)	no

Also known as: cutis laxa · elastolysis · generalised elastolysis · generalized elastolysis

Data availability: 124 ClinVar variants · 1 GenCC gene-disease record · 9 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › cutis laxa

Subtypes (2): acquired cutis laxa, inherited cutis laxa

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

124 retrieved; paginated sample, class counts are floors:

48 uncertain significance, 27 conflicting classifications of pathogenicity, 16 benign, 11 pathogenic/likely pathogenic, 10 benign/likely benign, 6 likely pathogenic, 5 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
845	NM_012463.4(ATP6V0A2):c.187C>T (p.Arg63Ter)	ATP6V0A2	Pathogenic	criteria provided, multiple submitters, no conflicts
417760	NM_001696.4(ATP6V1E1):c.634C>T (p.Arg212Trp)	ATP6V1E1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048805	NM_001039348.3(EFEMP1):c.1201C>T (p.Arg401Ter)	EFEMP1	Pathogenic	criteria provided, single submitter
286400	NM_012463.4(ATP6V0A2):c.78dup (p.Ser27fs)	LOC130009117	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13190	NM_006907.4(PYCR1):c.797G>A (p.Arg266Gln)	PYCR1	Pathogenic	criteria provided, multiple submitters, no conflicts
13196	NM_006907.4(PYCR1):c.355C>G (p.Arg119Gly)	PYCR1	Pathogenic	criteria provided, multiple submitters, no conflicts
13197	NM_006907.4(PYCR1):c.356G>A (p.Arg119His)	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13198	NM_006907.4(PYCR1):c.752G>A (p.Arg251His)	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704556	NM_006907.4(PYCR1):c.575del (p.Gly192fs)	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1878382	NM_006907.4(PYCR1):c.151A>T (p.Lys51Ter)	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3069061	NM_006907.4(PYCR1):c.148del (p.Gly49_Val50insTer)	PYCR1	Pathogenic	criteria provided, single submitter
325904	NM_006907.4(PYCR1):c.633+1G>C	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449091	NM_006907.4(PYCR1):c.535G>A (p.Ala179Thr)	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488456	NM_006907.4(PYCR1):c.355C>T (p.Arg119Cys)	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521586	NM_006907.4(PYCR1):c.138+1G>A	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68789	NM_006907.4(PYCR1):c.616G>A (p.Gly206Arg)	PYCR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2429237	NM_012463.4(ATP6V0A2):c.2393del (p.Ala798fs)	ATP6V0A2	Likely pathogenic	criteria provided, single submitter
374067	NM_000093.5(COL5A1):c.2903del (p.Pro968fs)	COL5A1	Likely pathogenic	criteria provided, single submitter
3075819	NM_016938.5(EFEMP2):c.1009C>T (p.Arg337Ter)	EFEMP2	Likely pathogenic	criteria provided, single submitter
183343	NM_198841.4(FAM120AOS):c.743C>T (p.Thr248Ile)	FAM120AOS	Likely pathogenic	no assertion criteria provided
995862	NM_002317.7(LOX):c.1021A>C (p.Thr341Pro)	LOX	Likely pathogenic	criteria provided, single submitter
1804749	NM_001042545.2(LTBP4):c.1426+1G>T	LTBP4	Likely pathogenic	criteria provided, single submitter
6559	NM_001171.6(ABCC6):c.3421C>T (p.Arg1141Ter)	ABCC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
21453	NM_006329.4(FBLN5):c.604G>A (p.Gly202Arg)	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218359	NM_006329.4(FBLN5):c.268G>A (p.Gly90Ser)	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218360	NM_006329.4(FBLN5):c.376G>A (p.Val126Met)	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287193	NM_006329.4(FBLN5):c.621T>C (p.Asp207=)	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
314861	NM_006329.4(FBLN5):c.*648G>A	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
314871	NM_006329.4(FBLN5):c.1191G>A (p.Thr397=)	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
314874	NM_006329.4(FBLN5):c.989+9C>T	FBLN5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 21 · 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
ATP6V0A2	Orphanet:2834	Wrinkly skin syndrome
ATP6V0A2	Orphanet:357074	Autosomal recessive cutis laxa type 2, classic type
SLC39A13	Orphanet:157965	SLC39A13-related spondylodysplastic Ehlers-Danlos syndrome
COL5A1	Orphanet:287	Classical Ehlers-Danlos syndrome
EFEMP2	Orphanet:314718	Lethal arteriopathy syndrome due to fibulin-4 deficiency
EFEMP2	Orphanet:90349	Autosomal recessive cutis laxa type 1
EFEMP2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBLN5	Orphanet:280598	Hereditary sensorimotor neuropathy with hyperelastic skin
FBLN5	Orphanet:90348	Autosomal dominant cutis laxa
FBLN5	Orphanet:90349	Autosomal recessive cutis laxa type 1
ABCC6	Orphanet:51608	Generalized arterial calcification of infancy
ABCC6	Orphanet:758	Pseudoxanthoma elasticum
LOX	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
LTBP4	Orphanet:221145	Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies
LTBP4	Orphanet:98896	Duchenne muscular dystrophy
ATP6V1E1	Orphanet:357074	Autosomal recessive cutis laxa type 2, classic type
PYCR1	Orphanet:2078	Geroderma osteodysplastica
PYCR1	Orphanet:293633	PYCR1-related De Barsy syndrome
PYCR1	Orphanet:357064	Autosomal recessive cutis laxa type 2B

Cohort genes → proteins

12 cohort genes, 12 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	gencc,clinvar
ATP6V0A2	HGNC:18481	ENSG00000185344	Q9Y487	V-type proton ATPase 116 kDa subunit a 2	clinvar
SLC39A13	HGNC:20859	ENSG00000165915	Q96H72	Zinc transporter ZIP13	clinvar
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	clinvar
FAM120AOS	HGNC:23389	ENSG00000188938	Q5T036	Uncharacterized protein FAM120AOS	clinvar
EFEMP2	HGNC:3219	ENSG00000172638	O95967	EGF-containing fibulin-like extracellular matrix protein 2	clinvar
FBLN5	HGNC:3602	ENSG00000140092	Q9UBX5	Fibulin-5	clinvar
ABCC6	HGNC:57	ENSG00000091262	O95255	ATP-binding cassette sub-family C member 6	clinvar
LOX	HGNC:6664	ENSG00000113083	P28300	Protein-lysine 6-oxidase	clinvar
LTBP4	HGNC:6717	ENSG00000090006	Q8N2S1	Latent-transforming growth factor beta-binding protein 4	clinvar
ATP6V1E1	HGNC:857	ENSG00000131100	P36543	V-type proton ATPase subunit E 1	clinvar
PYCR1	HGNC:9721	ENSG00000183010	P32322	Pyrroline-5-carboxylate reductase 1, mitochondrial	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.
ATP6V0A2	V-type proton ATPase 116 kDa subunit a 2	Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
SLC39A13	Zinc transporter ZIP13	Functions as a zinc transporter transporting Zn(2+) from the Golgi apparatus to the cytosol and thus influences the zinc level at least in areas of the cytosol.
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
EFEMP2	EGF-containing fibulin-like extracellular matrix protein 2	Plays a crucial role in elastic fiber formation in tissue, and in the formation of ultrastructural connections between elastic laminae and smooth muscle cells in the aorta, therefore participates in terminal differentiation and maturation…
FBLN5	Fibulin-5	Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN.
ABCC6	ATP-binding cassette sub-family C member 6	ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells.
LOX	Protein-lysine 6-oxidase	Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin.
LTBP4	Latent-transforming growth factor beta-binding protein 4	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.
ATP6V1E1	V-type proton ATPase subunit E 1	Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
PYCR1	Pyrroline-5-carboxylate reductase 1, mitochondrial	Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 8 · Druggable fraction: 0.33

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
Transporter	1	6.5×	0.216
Enzyme (other)	3	3.0×	0.216
Other/Unknown	8	1.2×	0.325

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
ATP6V0A2	Enzyme (other)	yes	7.1.2.1	V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka
SLC39A13	Other/Unknown	no		ZIP
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
FAM120AOS	Other/Unknown	no
EFEMP2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
FBLN5	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ABCC6	Transporter	yes	7.6.2.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP
LOX	Enzyme (other)	yes	1.4.3.13	Lysyl_oxidase, Lysyl_oxidase_CS,
LTBP4	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ATP6V1E1	Other/Unknown	no		ATPase_V1_Esu, ATPase_E_C
PYCR1	Enzyme (other)	yes	1.5.1.2	Pyrroline-COOH_reductase, 6-PGluconate_DH-like_C_sf, P5C_Rdtase_cat_N

Expression context

Cohort genes with no expression data: 0.

12 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)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	5
thoracic aorta	3
ascending aorta	3
descending thoracic aorta	2
right coronary artery	2
tendon of biceps brachii	2
skin of leg	1
sural nerve	1
metanephros cortex	1
periodontal ligament	1
adenohypophysis	1
cardiac muscle of right atrium	1
ileal mucosa	1
duodenum	1
liver	1
right lobe of liver	1
calcaneal tendon	1
tibia	1
nerve	1
tibial nerve	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
ATP6V0A2	239	ubiquitous	marker	skin of leg, sural nerve, stromal cell of endometrium
SLC39A13	248	ubiquitous	marker	metanephros cortex, ascending aorta, thoracic aorta
COL5A1	248	ubiquitous	marker	stromal cell of endometrium, periodontal ligament, tendon of biceps brachii
FAM120AOS	256	ubiquitous	marker	cardiac muscle of right atrium, adenohypophysis, ileal mucosa
EFEMP2	289	ubiquitous	marker	stromal cell of endometrium, tendon of biceps brachii, ascending aorta
FBLN5	261	ubiquitous	marker	thoracic aorta, ascending aorta, descending thoracic aorta
ABCC6	136		marker	right lobe of liver, liver, duodenum
LOX	242	ubiquitous	marker	stromal cell of endometrium, calcaneal tendon, tibia
LTBP4	264	ubiquitous	marker	nerve, tibial nerve, right coronary artery
ATP6V1E1	303	ubiquitous	marker	middle temporal gyrus, prefrontal cortex, pons
PYCR1	224	ubiquitous	marker	stromal cell of endometrium, body of pancreas, parotid gland

Protein interactions among cohort

Intra-cohort edges: 11.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LOX	5,479
EFEMP1	2,988
COL5A1	2,600
FBLN5	2,301
PYCR1	2,239
EFEMP2	2,219
ATP6V1E1	2,187
ATP6V0A2	2,076
LTBP4	1,984
SLC39A13	1,093

Intra-cohort edges

A	B	Sources
ATP6V0A2	ATP6V1E1	intact, string_interaction
ATP6V0A2	EFEMP2	string_interaction
ATP6V0A2	FBLN5	string_interaction
ATP6V0A2	PYCR1	string_interaction
EFEMP2	FBLN5	intact
EFEMP2	LOX	intact, string_interaction
EFEMP2	LTBP4	string_interaction
EFEMP2	PYCR1	string_interaction
FBLN5	LOX	intact, string_interaction
FBLN5	LTBP4	string_interaction
FBLN5	PYCR1	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PYCR1	P32322	47
ATP6V1E1	P36543	8
ABCC6	O95255	4
COL5A1	P20908	1
EFEMP2	O95967	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBLN5	Q9UBX5	83.69
ATP6V0A2	Q9Y487	81.94
EFEMP1	Q12805	77.67
SLC39A13	Q96H72	76.33
LOX	P28300	68.06
LTBP4	Q8N2S1	62.53
FAM120AOS	Q5T036	55.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 36. Enrichment computed across 12 evidence-associated genes (10 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 10 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	4	123.5×	7e-07	EFEMP1, EFEMP2, FBLN5, LTBP4
Elastic fibre formation	3	100.8×	5e-05	FBLN5, LOX, LTBP4
Insulin receptor recycling	2	76.1×	0.003	ATP6V0A2, ATP6V1E1
Transferrin endocytosis and recycling	2	73.7×	0.003	ATP6V0A2, ATP6V1E1
ROS and RNS production in phagocytes	2	67.2×	0.003	ATP6V0A2, ATP6V1E1
Defective ABCC6 causes PXE	1	1142.0×	0.005	ABCC6
Assembly of collagen fibrils and other multimeric structures	2	40.1×	0.006	COL5A1, LOX
Ion channel transport	2	19.2×	0.021	ATP6V0A2, ATP6V1E1
Extracellular matrix organization	2	12.6×	0.041	LOX, LTBP4
Glutamate and glutamine metabolism	1	81.6×	0.044	PYCR1
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	67.2×	0.048	ATP6V1E1
Fibronectin matrix formation	1	57.1×	0.048	COL5A1
Crosslinking of collagen fibrils	1	57.1×	0.048	LOX
Attachment of bacteria to epithelial cells	1	49.6×	0.050	COL5A1
Collagen formation	1	45.7×	0.050	LOX
ABC transporter disorders	1	43.9×	0.050	ABCC6
Syndecan interactions	1	42.3×	0.050	COL5A1
MET activates PTK2 signaling	1	38.1×	0.052	COL5A1
TGF-beta receptor signaling activates SMADs	1	32.6×	0.057	LTBP4
Collagen chain trimerization	1	25.9×	0.065	COL5A1
Signaling by PDGF	1	25.4×	0.065	COL5A1
NCAM1 interactions	1	24.8×	0.065	COL5A1
Developmental Lineage of Pancreatic Ductal Cells	1	22.8×	0.067	COL5A1
Signaling by TGF-beta Receptor Complex	1	20.0×	0.070	LTBP4
Amino acids regulate mTORC1	1	20.0×	0.070	ATP6V1E1
Collagen degradation	1	17.6×	0.076	COL5A1
Collagen biosynthesis and modifying enzymes	1	17.0×	0.076	COL5A1
Non-integrin membrane-ECM interactions	1	15.4×	0.080	COL5A1
ECM proteoglycans	1	15.0×	0.080	COL5A1
Disorders of transmembrane transporters	1	13.9×	0.083	ABCC6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
elastic fiber assembly	4	557.1×	3e-09	EFEMP2, FBLN5, LOX, LTBP4
connective tissue development	2	766.0×	1e-04	SLC39A13, LOX
regulation of transforming growth factor beta receptor signaling pathway	2	145.9×	0.003	LOX, LTBP4
ascending aorta development	1	1532.0×	0.006	LOX
descending aorta development	1	1532.0×	0.006	LOX
integrin biosynthetic process	1	1532.0×	0.006	COL5A1
intramembranous bone growth	1	1532.0×	0.006	FBLN5
positive regulation of smooth muscle cell-matrix adhesion	1	1532.0×	0.006	EFEMP2
regulation of platelet-derived growth factor receptor-beta signaling pathway	1	1532.0×	0.006	LOX
proton transmembrane transport	2	56.7×	0.006	ATP6V0A2, ATP6V1E1
regulation of macroautophagy	2	53.8×	0.006	ATP6V0A2, ATP6V1E1
inorganic diphosphate transport	1	766.0×	0.008	ABCC6
negative regulation of endodermal cell differentiation	1	766.0×	0.008	COL5A1
positive regulation of aortic smooth muscle cell differentiation	1	766.0×	0.008	EFEMP2
collagen fibril organization	2	40.9×	0.008	COL5A1, LOX
peptidyl-lysine oxidation	1	510.7×	0.011	LOX
post-embryonic eye morphogenesis	1	510.7×	0.011	EFEMP1
regulation of collagen fibril organization	1	510.7×	0.011	EFEMP2
tendon development	1	383.0×	0.011	COL5A1
hormone secretion	1	383.0×	0.011	LTBP4
eye morphogenesis	1	383.0×	0.011	COL5A1
aorta smooth muscle tissue morphogenesis	1	383.0×	0.011	EFEMP2
inhibition of non-skeletal tissue mineralization	1	383.0×	0.011	ABCC6
positive regulation of collagen fibril organization	1	383.0×	0.011	EFEMP2
platelet-derived growth factor receptor-beta signaling pathway	1	306.4×	0.012	LOX
regulation of bone development	1	306.4×	0.012	LOX
regulation of striated muscle tissue development	1	255.3×	0.013	LOX
L-proline biosynthetic process	1	255.3×	0.013	PYCR1
regulation of removal of superoxide radicals	1	255.3×	0.013	FBLN5
leukotriene transport	1	218.9×	0.015	ABCC6

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 10

Druggability breadth: 5 of 12 evidence-associated genes (42%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
LOX	PYRITHIONE
PYCR1	PARGYLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LOX	4	4
PYCR1	1	4
EFEMP1	0	0
ATP6V0A2	0	0
SLC39A13	0	0
COL5A1	0	0
FAM120AOS	0	0
EFEMP2	0	0
FBLN5	0	0
ABCC6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRITHIONE	4	LOX
ZILEUTON	4	LOX
DISULFIRAM	4	LOX
PARGYLINE	4	PYCR1
THIRAM	2	LOX

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LOX	15	Binding:15
PYCR1	12	Binding:12
ABCC6	10	Functional:9, Binding:1
ATP6V1E1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP6V0A2	7.1.2.1	P-type H+-exporting transporter
ABCC6	7.6.2.3	ABC-type glutathione-S-conjugate transporter
LOX	1.4.3.13	protein-lysine 6-oxidase
PYCR1	1.5.1.2	pyrroline-5-carboxylate reductase

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

5 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.

Compound	Max phase	Cohort target (bioactivity)
PYRITHIONE	4	LOX
ZILEUTON	4	LOX
DISULFIRAM	4	LOX
PARGYLINE	4	PYCR1
THIRAM	2	LOX

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	LOX, PYCR1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ABCC6
D	Druggable family + AlphaFold only, no drug	1	ATP6V0A2
E	Difficult family or no structure, no drug	8	EFEMP1, SLC39A13, COL5A1, FAM120AOS, EFEMP2, FBLN5, LTBP4, ATP6V1E1

Undrugged target profiles

10 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
EFEMP2	0	LOX, PYCR1
FBLN5	0	LOX
EFEMP1	0	—
ATP6V0A2	0	—
SLC39A13	0	—
COL5A1	0	—
FAM120AOS	0	—
ABCC6	10	—
LTBP4	0	—
ATP6V1E1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03887208	PHASE1/PHASE2	COMPLETED	Therapy of Scars and Cutis Laxa With Autologous Adipose Derived Mesenchymal Stem Cells
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT07614997	Not specified	NOT_YET_RECRUITING	Effectiveness and Safety of the Ulthera® System for Skin Laxity in the Lower Face, Submentum and Neck
NCT01293864	Not specified	TERMINATED	Structural Analysis of Human Tissue
NCT01658163	Not specified	COMPLETED	Use of 2-octyl-cyanoacrylate Together With a Self-adhering Mesh

Cohort genes: EFEMP1, ATP6V0A2, SLC39A13, COL5A1, FAM120AOS, EFEMP2, FBLN5, ABCC6, LOX, LTBP4, ATP6V1E1, PYCR1