Ehlers-Danlos syndrome, arthrochalasia type

Summary

Ehlers-Danlos syndrome, arthrochalasia type (MONDO:0007525) is a disease caused by variants in COL1A1 and COL1A2, with 5 cohort genes. The dominant Reactome pathway is Fibronectin matrix formation (3 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal genes: COL1A1 (GenCC Definitive), COL1A2 (GenCC Strong)
• Cohort genes: 5
• ClinVar variants: 233
• Phenotypes (HPO): 26

Clinical features

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0000963	Thin skin	Very frequent (80-99%)
HP:0000974	Hyperextensible skin	Very frequent (80-99%)
HP:0001001	Abnormality of subcutaneous fat tissue	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001373	Joint dislocation	Very frequent (80-99%)
HP:0001385	Hip dysplasia	Very frequent (80-99%)
HP:0001387	Joint stiffness	Very frequent (80-99%)
HP:0002300	Mutism	Very frequent (80-99%)
HP:0002381	Aphasia	Very frequent (80-99%)
HP:0002673	Coxa valga	Very frequent (80-99%)
HP:0002812	Coxa vara	Very frequent (80-99%)
HP:0002827	Hip dislocation	Very frequent (80-99%)
HP:0003510	Severe short stature	Very frequent (80-99%)
HP:0005743	Avascular necrosis of the capital femoral epiphysis	Very frequent (80-99%)
HP:0010529	Echolalia	Very frequent (80-99%)
HP:0010547	Muscle flaccidity	Very frequent (80-99%)
HP:0100699	Scarring	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0000278	Retrognathia	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0100541	Femoral hernia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, arthrochalasia type
Mondo ID	MONDO:0007525
MeSH	C562625
Orphanet	1899
DOID	DOID:0080727
NCIT	C125701
SNOMED CT	4170004
UMLS	C4551623
MedGen	1645042
GARD	0002084
Is cancer (heuristic)	no

Also known as: AEDS · arthrochalasia EDS · arthrochalasia Ehlers-Danlos syndrome · arthrochalasis multiplex congenita · EDS 7A · EDS 7B · EDS VII · EDS7A (formerly) · EDSARTH1 · Ehlers-Danlos syndrome type 7 · Ehlers-Danlos syndrome type 7A (formerly) · Ehlers-Danlos syndrome, arthrochalasia type · Ehlers-Danlos syndrome, type VII

Data availability: 233 ClinVar variants · 6 GenCC gene-disease records · 8 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Ehlers-Danlos syndrome › Ehlers-Danlos syndrome, arthrochalasia type

Related subtypes (24): Ehlers-Danlos syndrome, classic type, Ehlers-Danlos syndrome, hypermobility type, Ehlers-Danlos syndrome, spondylodysplastic type, Ehlers-Danlos syndrome, periodontitis type, Ehlers-Danlos syndrome, autosomal dominant, type unspecified, joint laxity, familial, Ehlers-Danlos syndrome, fibronectinemic type, Ehlers-Danlos syndrome, dermatosparaxis type, brittle cornea syndrome, X-linked Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, musculocontractural type, Ehlers-Danlos syndrome due to tenascin-X deficiency, Ehlers-Danlos syndrome, Beasley-Cohen type, Ehlers-Danlos syndrome, kyphoscoliotic type, 2, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Ehlers-Danlos syndrome, vascular-like type, Ehlers-Danlos/osteogenesis imperfecta syndrome, Ehlers-Danlos syndrome, vascular type, spondylodysplastic Ehlers-Danlos syndrome, Bethlem myopathy 2, Ehlers-Danlos syndrome, classic-like, 2, COL1A1-related Ehlers-Danlos syndrome, COL1A2-related Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, classic-like, 3

Subtypes (2): Ehlers-Danlos syndrome type 7A, Ehlers-Danlos syndrome, arthrochalasia type, 2

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

233 retrieved; paginated sample, class counts are floors:

90 conflicting classifications of pathogenicity, 48 uncertain significance, 26 pathogenic, 26 benign/likely benign, 22 benign, 16 pathogenic/likely pathogenic, 4 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076006	NM_000088.4(COL1A1):c.288del (p.Asp97fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1254747	NM_000088.4(COL1A1):c.1177C>T (p.Gln393Ter)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342741	NM_000088.4(COL1A1):c.1444G>A (p.Gly482Arg)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1431093	NM_000088.4(COL1A1):c.1667del (p.Pro556fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17311	NM_000088.4(COL1A1):c.543G>A (p.Met181Ile)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17312	NM_000088.4(COL1A1):c.994G>A (p.Gly332Arg)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17313	NM_000088.4(COL1A1):c.3541G>A (p.Gly1181Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17339	NM_000088.4(COL1A1):c.472-1G>A	COL1A1	Pathogenic	no assertion criteria provided
17343	NM_000088.4(COL1A1):c.934C>T (p.Arg312Cys)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17347	NM_000088.4(COL1A1):c.3040C>T (p.Arg1014Cys)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17350	NM_000088.4(COL1A1):c.472-2A>T	COL1A1	Pathogenic	no assertion criteria provided
1805989	NM_000088.4(COL1A1):c.3540del (p.Gly1181fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2772795	NM_000088.4(COL1A1):c.2597del (p.Gly866fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2780397	NM_000088.4(COL1A1):c.598G>A (p.Gly200Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2849807	NM_000088.4(COL1A1):c.159G>A (p.Trp53Ter)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
287320	NM_000088.4(COL1A1):c.2089C>T (p.Arg697Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
3382929	NM_000088.4(COL1A1):c.635G>A (p.Gly212Glu)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35907	NM_000088.4(COL1A1):c.2062C>T (p.Gln688Ter)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35920	NM_000088.4(COL1A1):c.3076C>T (p.Arg1026Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425580	NM_000088.4(COL1A1):c.1821+1G>A	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425583	NM_000088.4(COL1A1):c.2343+1G>A	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425597	NM_000088.4(COL1A1):c.1243C>T (p.Arg415Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425599	NM_000088.4(COL1A1):c.1299+1G>A	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425606	NM_000088.4(COL1A1):c.2155G>A (p.Gly719Ser)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
425618	NM_000088.4(COL1A1):c.3226G>A (p.Gly1076Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425639	NM_000088.4(COL1A1):c.769G>A (p.Gly257Arg)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
447141	NM_000088.4(COL1A1):c.2362G>A (p.Gly788Ser)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
450546	NM_000088.4(COL1A1):c.985G>C (p.Gly329Arg)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
456724	NM_000088.4(COL1A1):c.1012G>A (p.Gly338Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
456753	NM_000088.4(COL1A1):c.2644C>T (p.Arg882Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 41 · Orphanet: 20 · 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
COL1A1	Definitive	Autosomal dominant	Ehlers-Danlos syndrome, classic type	20
COL1A2	Definitive	Autosomal recessive	Ehlers-Danlos syndrome, cardiac valvular type	21

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL1A1	Orphanet:1310	Caffey disease
COL1A1	Orphanet:1899	Arthrochalasia Ehlers-Danlos syndrome
COL1A1	Orphanet:216796	Osteogenesis imperfecta type 1
COL1A1	Orphanet:216804	Osteogenesis imperfecta type 2
COL1A1	Orphanet:216812	Osteogenesis imperfecta type 3
COL1A1	Orphanet:216820	Osteogenesis imperfecta type 4
COL1A1	Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome
COL1A1	Orphanet:287	Classical Ehlers-Danlos syndrome
COL1A1	Orphanet:31112	Dermatofibrosarcoma protuberans
COL1A1	Orphanet:314029	High bone mass osteogenesis imperfecta
COL1A2	Orphanet:1899	Arthrochalasia Ehlers-Danlos syndrome
COL1A2	Orphanet:216796	Osteogenesis imperfecta type 1
COL1A2	Orphanet:216804	Osteogenesis imperfecta type 2
COL1A2	Orphanet:216812	Osteogenesis imperfecta type 3
COL1A2	Orphanet:216820	Osteogenesis imperfecta type 4
COL1A2	Orphanet:230851	Cardiac-valvular Ehlers-Danlos syndrome
COL1A2	Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome
COL1A2	Orphanet:314029	High bone mass osteogenesis imperfecta
COL5A2	Orphanet:287	Classical Ehlers-Danlos syndrome
ALB	Orphanet:86816	Congenital analbuminemia

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL1A1	HGNC:2197	ENSG00000108821	P02452	Collagen alpha-1(I) chain	gencc,clinvar
COL1A2	HGNC:2198	ENSG00000164692	P08123	Collagen alpha-2(I) chain	gencc,clinvar
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	clinvar
FBF1	HGNC:24674	ENSG00000188878	Q8TES7	Fas-binding factor 1	clinvar
ALB	HGNC:399	ENSG00000163631	P02768	Albumin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL1A1	Collagen alpha-1(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).
COL1A2	Collagen alpha-2(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
FBF1	Fas-binding factor 1	Keratin-binding protein required for epithelial cell polarization.
ALB	Albumin	Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 5 · 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	5	1.8×	0.054

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL1A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
COL1A2	Other/Unknown	no		Fib_collagen_C, Collagen, Collagen_superfamily
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
FBF1	Other/Unknown	no		FBF1, FBF1_C
ALB	Other/Unknown	no		ALB/AFP/VDB, Serum_albumin_N, Serum_albumin_CS

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
periodontal ligament	3
stromal cell of endometrium	3
skin of hip	2
tendon of biceps brachii	1
left testis	1
right lobe of thyroid gland	1
right testis	1
body of pancreas	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL1A1	298	ubiquitous	marker	stromal cell of endometrium, skin of hip, periodontal ligament
COL1A2	295	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, skin of hip
COL5A2	266	ubiquitous	marker	tendon of biceps brachii, periodontal ligament, stromal cell of endometrium
FBF1	163	ubiquitous	yes	right testis, left testis, right lobe of thyroid gland
ALB	178	tissue_specific	marker	right lobe of liver, liver, body of pancreas

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALB	11,544
COL1A1	5,341
COL5A2	2,286
FBF1	1,413
COL1A2	179

Intra-cohort edges

A	B	Sources
COL1A1	COL1A2	intact
COL1A1	COL5A2	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALB	P02768	189
COL1A1	P02452	14
COL1A2	P08123	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBF1	Q8TES7	64.11
COL5A2	P05997	53.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 63. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fibronectin matrix formation	3	342.6×	3e-06	COL1A1, COL1A2, COL5A2
Syndecan interactions	3	253.8×	3e-06	COL1A1, COL1A2, COL5A2
MET activates PTK2 signaling	3	228.4×	3e-06	COL1A1, COL1A2, COL5A2
Defective VWF binding to collagen type I	2	1522.7×	7e-06	COL1A1, COL1A2
Collagen chain trimerization	3	155.7×	7e-06	COL1A1, COL1A2, COL5A2
Enhanced cleavage of VWF variant by ADAMTS13	2	1142.0×	7e-06	COL1A1, COL1A2
Defective VWF cleavage by ADAMTS13 variant	2	1142.0×	7e-06	COL1A1, COL1A2
Developmental Lineage of Pancreatic Ductal Cells	3	137.0×	7e-06	COL1A1, COL1A2, COL5A2
Assembly of collagen fibrils and other multimeric structures	3	120.2×	8e-06	COL1A1, COL1A2, COL5A2
Collagen degradation	3	105.4×	1e-05	COL1A1, COL1A2, COL5A2
Collagen biosynthesis and modifying enzymes	3	102.3×	1e-05	COL1A1, COL1A2, COL5A2
Enhanced binding of GP1BA variant to VWF multimer:collagen	2	652.6×	1e-05	COL1A1, COL1A2
Defective binding of VWF variant to GPIb:IX:V	2	652.6×	1e-05	COL1A1, COL1A2
Non-integrin membrane-ECM interactions	3	92.6×	1e-05	COL1A1, COL1A2, COL5A2
ECM proteoglycans	3	90.2×	1e-05	COL1A1, COL1A2, COL5A2
Integrin cell surface interactions	3	80.6×	2e-05	COL1A1, COL1A2, COL5A2
GP1b-IX-V activation signalling	2	380.7×	4e-05	COL1A1, COL1A2
Anchoring fibril formation	2	304.5×	6e-05	COL1A1, COL1A2
Platelet Adhesion to exposed collagen	2	268.7×	7e-05	COL1A1, COL1A2
Scavenging by Class A Receptors	2	240.4×	8e-05	COL1A1, COL1A2
Crosslinking of collagen fibrils	2	228.4×	9e-05	COL1A1, COL1A2
Platelet Aggregation (Plug Formation)	2	175.7×	1e-04	COL1A1, COL1A2
GPVI-mediated activation cascade	2	123.5×	3e-04	COL1A1, COL1A2
Cell surface interactions at the vascular wall	2	38.1×	0.003	COL1A1, COL1A2
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	2	34.9×	0.003	COL1A1, COL1A2
Ciprofloxacin ADME	1	456.8×	0.005	ALB
Metabolism of porphyrins	1	285.5×	0.008	ALB
Prednisone ADME	1	253.8×	0.009	ALB
HDL remodeling	1	228.4×	0.009	ALB
Scavenging of heme from plasma	1	175.7×	0.012	ALB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to amino acid stimulus	3	183.8×	2e-05	COL1A1, COL1A2, COL5A2
collagen fibril organization	3	134.8×	3e-05	COL1A1, COL1A2, COL5A2
skin morphogenesis	2	561.7×	7e-05	COL1A1, COL1A2
skeletal system development	3	75.5×	7e-05	COL1A1, COL1A2, COL5A2
blood vessel development	2	149.8×	8e-04	COL1A1, COL1A2
protein heterotrimerization	1	3370.4×	0.003	COL1A2
cellular response to vitamin E	1	3370.4×	0.003	COL1A1
bilirubin transport	1	1685.2×	0.004	ALB
cellular response to fluoride	1	1685.2×	0.004	COL1A1
negative regulation of endodermal cell differentiation	1	1685.2×	0.004	COL5A2
tooth mineralization	1	1123.5×	0.005	COL1A1
eye morphogenesis	1	842.6×	0.005	COL5A2
cellular response to calcium ion starvation	1	842.6×	0.005	ALB
cellular response to acetaldehyde	1	674.1×	0.006	COL1A1
intramembranous ossification	1	561.7×	0.007	COL1A1
cartilage development involved in endochondral bone morphogenesis	1	481.5×	0.008	COL1A1
apical junction assembly	1	421.3×	0.008	FBF1
bone trabecula formation	1	421.3×	0.008	COL1A1
negative regulation of mitochondrial depolarization	1	374.5×	0.008	ALB
collagen-activated tyrosine kinase receptor signaling pathway	1	259.3×	0.011	COL1A1
establishment of epithelial cell polarity	1	240.7×	0.011	FBF1
response to hyperoxia	1	224.7×	0.011	COL1A1
negative regulation of cell-substrate adhesion	1	210.7×	0.011	COL1A1
collagen metabolic process	1	210.7×	0.011	COL1A2
collagen biosynthetic process	1	210.7×	0.011	COL1A1
extracellular matrix assembly	1	187.2×	0.012	COL1A2
response to steroid hormone	1	168.5×	0.013	COL1A1
endochondral ossification	1	108.7×	0.019	COL1A1
cellular response to fibroblast growth factor stimulus	1	108.7×	0.019	COL1A1
odontogenesis	1	105.3×	0.019	COL1A2

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 5 evidence-associated genes (80%) 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
ALB	DIAZEPAM

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALB	36	4
COL1A1	0	0
COL1A2	0	0
COL5A2	0	0
FBF1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIAZEPAM	4	ALB
EVANS BLUE	4	ALB
ZIDOVUDINE	4	ALB
ABACAVIR	4	ALB
DICLOFENAC	4	ALB
LAMIVUDINE	4	ALB
MINOCYCLINE	4	ALB
LINCOMYCIN	4	ALB
DIDANOSINE	4	ALB
WARFARIN	4	ALB
CEFOTAXIME	4	ALB
TAFAMIDIS	4	ALB
VANCOMYCIN	4	ALB
NOVOBIOCIN	4	ALB
RIFAMPIN	4	ALB
FUSIDIC ACID	4	ALB
BENZBROMARONE	4	ALB
ACORAMIDIS	4	ALB
OFLOXACIN	4	ALB
BICALUTAMIDE	4	ALB
BRILLIANT BLUE G FREE ACID	4	ALB
VISMODEGIB	4	ALB
IBUPROFEN	4	ALB
ERYTHROMYCIN	4	ALB
ALPIDEM	4	ALB
OXAZEPAM	4	ALB
INDOMETHACIN	4	ALB
CHLORPROMAZINE	4	ALB
TOLBUTAMIDE	4	ALB
ZALCITABINE	4	ALB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ALB	953	ADMET:767, Binding:168, Functional:18
COL1A1	8	Binding:8
COL1A2	4	Functional:4

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ALB	953

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
DIAZEPAM	4	ALB
EVANS BLUE	4	ALB
ZIDOVUDINE	4	ALB
ABACAVIR	4	ALB
DICLOFENAC	4	ALB
LAMIVUDINE	4	ALB
MINOCYCLINE	4	ALB
LINCOMYCIN	4	ALB
DIDANOSINE	4	ALB
WARFARIN	4	ALB
CEFOTAXIME	4	ALB
TAFAMIDIS	4	ALB
VANCOMYCIN	4	ALB
NOVOBIOCIN	4	ALB
RIFAMPIN	4	ALB
FUSIDIC ACID	4	ALB
BENZBROMARONE	4	ALB
ACORAMIDIS	4	ALB
OFLOXACIN	4	ALB
BICALUTAMIDE	4	ALB
BRILLIANT BLUE G FREE ACID	4	ALB
VISMODEGIB	4	ALB
IBUPROFEN	4	ALB
ERYTHROMYCIN	4	ALB
ALPIDEM	4	ALB
OXAZEPAM	4	ALB
INDOMETHACIN	4	ALB
CHLORPROMAZINE	4	ALB
TOLBUTAMIDE	4	ALB
ZALCITABINE	4	ALB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ALB
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	4	COL1A1, COL1A2, COL5A2, FBF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL1A1	8	—
COL1A2	4	—
COL5A2	0	—
FBF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.