Ehlers-Danlos syndrome, classic type, 1

Summary

Ehlers-Danlos syndrome, classic type, 1 (MONDO:0019567) is a disease caused by COL5A1 (GenCC Strong), with 9 cohort genes. The dominant Reactome pathway is Fibronectin matrix formation (5 cohort genes).

At a glance

• Causal gene: COL5A1 (GenCC Strong)
• Cohort genes: 9
• ClinVar variants: 6,694

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, classic type, 1
Mondo ID	MONDO:0019567
MeSH	C536194
OMIM	130000
Orphanet	90309
DOID	DOID:14720
NCIT	C125696
SNOMED CT	83470009
UMLS	C0268335
MedGen	78660
GARD	0025140
Is cancer (heuristic)	no

Also known as: EDS I · EDSCL1 · Ehlers-Danlos syndrome, classic type, 1 · Ehlers-Danlos syndrome, type I

Data availability: 6,694 ClinVar variants · 1 GenCC gene-disease record · 28 cell lines.

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 › Ehlers-Danlos syndrome, classic type › Ehlers-Danlos syndrome, classic type, 1

Related subtypes (1): Ehlers-Danlos syndrome, classic 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

600 retrieved; paginated sample, class counts are floors:

176 likely benign, 166 uncertain significance, 91 benign/likely benign, 81 conflicting classifications of pathogenicity, 41 pathogenic, 31 benign, 7 likely pathogenic, 7 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031384	NM_000089.4(COL1A2):c.2324G>A (p.Gly775Glu)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066123	NM_000089.4(COL1A2):c.1388G>C (p.Gly463Ala)	COL1A2	Pathogenic	criteria provided, single submitter
1067157	NM_000089.4(COL1A2):c.2603G>C (p.Gly868Ala)	COL1A2	Pathogenic	criteria provided, single submitter
1067319	NM_000089.4(COL1A2):c.3170G>A (p.Gly1057Asp)	COL1A2	Pathogenic	criteria provided, single submitter
1068896	NM_000089.4(COL1A2):c.2755G>A (p.Gly919Ser)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069621	NM_000089.4(COL1A2):c.3238C>T (p.Arg1080Ter)	COL1A2	Pathogenic	criteria provided, single submitter
1071305	NM_000089.4(COL1A2):c.821G>A (p.Gly274Asp)	COL1A2	Pathogenic	criteria provided, single submitter
1071306	NM_000089.4(COL1A2):c.857G>C (p.Gly286Ala)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071307	NM_000089.4(COL1A2):c.1045G>A (p.Gly349Ser)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1071308	NM_000089.4(COL1A2):c.1981G>T (p.Gly661Cys)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1075256	NM_000089.4(COL1A2):c.2215G>C (p.Gly739Arg)	COL1A2	Pathogenic	criteria provided, single submitter
1075257	NM_000089.4(COL1A2):c.2413G>T (p.Gly805Cys)	COL1A2	Pathogenic	criteria provided, single submitter
1098566	NM_000089.4(COL1A2):c.3233G>A (p.Gly1078Asp)	COL1A2	Pathogenic	criteria provided, single submitter
1163008	NM_000089.4(COL1A2):c.3196G>A (p.Gly1066Ser)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1200401	NM_000089.4(COL1A2):c.792G>A (p.Lys264=)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1203633	NM_000089.4(COL1A2):c.1972G>T (p.Gly658Cys)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1223742	NM_000089.4(COL1A2):c.2206G>T (p.Gly736Cys)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1224306	NM_000089.4(COL1A2):c.1774G>A (p.Gly592Ser)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1314966	NM_000089.4(COL1A2):c.2152G>A (p.Gly718Ser)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1343353	NM_000089.4(COL1A2):c.2701G>A (p.Gly901Ser)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1349117	NM_000089.4(COL1A2):c.830G>C (p.Gly277Ala)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1365880	NM_000089.4(COL1A2):c.3276del (p.Gly1093fs)	COL1A2	Pathogenic	criteria provided, single submitter
1367319	NM_000089.4(COL1A2):c.3359A>G (p.Asp1120Gly)	COL1A2	Pathogenic	criteria provided, single submitter
1066734	NC_000002.11:g.(?189839206)(189950508_?)del	COL3A1	Pathogenic/Likely pathogenic	criteria provided, single submitter
1059268	NM_000093.5(COL5A1):c.74T>G (p.Leu25Arg)	COL5A1	Pathogenic	criteria provided, single submitter
1068592	NC_000009.11:g.(?137534024)(137620663_?)del	COL5A1	Pathogenic	criteria provided, single submitter
1068593	NC_000009.11:g.(?137582748)(137677904_?)del	COL5A1	Pathogenic	criteria provided, single submitter
1069321	NM_000093.5(COL5A1):c.5175_5200dup (p.Leu1734delinsArgTyrArgTer)	COL5A1	Pathogenic	criteria provided, single submitter
1070542	NM_000093.5(COL5A1):c.4088del (p.Gly1363fs)	COL5A1	Pathogenic	criteria provided, single submitter
1070824	NM_000093.5(COL5A1):c.3631C>T (p.Gln1211Ter)	COL5A1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 30 · 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
COL5A1	Definitive	Autosomal dominant	Ehlers-Danlos syndrome, classic type	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL5A1	Orphanet:287	Classical Ehlers-Danlos syndrome
DNAJB6	Orphanet:34516	DNAJB6-related limb-girdle muscular dystrophy D1
DNAJB6	Orphanet:708126	DNAJB6-related distal myopathy
KCNT1	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
KCNT1	Orphanet:98784	Sleep-related hypermotor epilepsy
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
COL3A1	Orphanet:231160	Familial cerebral saccular aneurysm
COL3A1	Orphanet:2500	Acrogeria
COL3A1	Orphanet:286	Vascular Ehlers-Danlos syndrome
COL3A1	Orphanet:636941	Vascular Ehlers-Danlos-polymicrogyria syndrome
COL3A1	Orphanet:86	Familial abdominal aortic aneurysm
COL5A2	Orphanet:287	Classical Ehlers-Danlos syndrome
AEBP1	Orphanet:536532	Classical-like Ehlers-Danlos syndrome type 2

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	gencc,clinvar
DNAJB6	HGNC:14888	ENSG00000105993	O75190	DnaJ homolog subfamily B member 6	clinvar
CASD1	HGNC:16014	ENSG00000127995	Q96PB1	N-acetylneuraminate (7)9-O-acetyltransferase	clinvar
KCNT1	HGNC:18865	ENSG00000107147	Q5JUK3	Potassium channel subfamily T member 1	clinvar
COL1A1	HGNC:2197	ENSG00000108821	P02452	Collagen alpha-1(I) chain	clinvar
COL1A2	HGNC:2198	ENSG00000164692	P08123	Collagen alpha-2(I) chain	clinvar
COL3A1	HGNC:2201	ENSG00000168542	P02461	Collagen alpha-1(III) chain	clinvar
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	clinvar
AEBP1	HGNC:303	ENSG00000106624	Q8IUX7	Adipocyte enhancer-binding protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
DNAJB6	DnaJ homolog subfamily B member 6	Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70.
CASD1	N-acetylneuraminate (7)9-O-acetyltransferase	Key enzyme in the biosynthesis of O-acetylated (O-Ac) sialoglycans such as gangliosides O-AcGD3 and O-AcGD2, which affect various processes such as cell-cell interactions, host-pathogen recognition.
KCNT1	Potassium channel subfamily T member 1	Sodium-activated K(+) channel.
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).
COL3A1	Collagen alpha-1(III) chain	Collagen type III occurs in most soft connective tissues along with type I collagen.
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
AEBP1	Adipocyte enhancer-binding protein 1	As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 6 · 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
Ion channel	1	12.4×	0.312
Protease	1	4.1×	0.441
Other/Unknown	6	1.2×	0.507
Enzyme (other)	1	1.3×	0.543

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
DNAJB6	Other/Unknown	no		DnaJ_domain, DnaJ_domain_CS, J_dom_sf
CASD1	Enzyme (other)	yes	2.3.1.45	Cas1_AcylTrans_dom, Cyclin-like_sf, NXPE4_C
KCNT1	Ion channel	yes		RCK_N, K_chnl_BK_asu, K_chnl_dom
COL1A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
COL1A2	Other/Unknown	no		Fib_collagen_C, Collagen, Collagen_superfamily
COL3A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
AEBP1	Protease	yes		FA58C, Peptidase_M14, CarboxyPept-like_regulatory

Expression context

Cohort genes with no expression data: 0.

9 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
periodontal ligament	4
stromal cell of endometrium	4
tendon of biceps brachii	3
skin of hip	3
cortical plate	1
ganglionic eminence	1
primordial germ cell in gonad	1
Ammon’s horn	1
adrenal tissue	1
postcentral gyrus	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
parietal pleura	1
visceral pleura	1
ascending aorta	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL5A1	248	ubiquitous	marker	stromal cell of endometrium, periodontal ligament, tendon of biceps brachii
DNAJB6	283	ubiquitous	marker	cortical plate, primordial germ cell in gonad, ganglionic eminence
CASD1	278	ubiquitous	marker	adrenal tissue, postcentral gyrus, Ammon’s horn
KCNT1	153	tissue_specific	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
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
COL3A1	281	ubiquitous	marker	skin of hip, parietal pleura, visceral pleura
COL5A2	266	ubiquitous	marker	tendon of biceps brachii, periodontal ligament, stromal cell of endometrium
AEBP1	273	ubiquitous	marker	tendon of biceps brachii, thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL1A1	5,341
COL3A1	3,629
DNAJB6	3,518
COL5A1	2,600
COL5A2	2,286
KCNT1	1,562
AEBP1	1,060
CASD1	426
COL1A2	179

Intra-cohort edges

A	B	Sources
AEBP1	COL5A1	string_interaction
AEBP1	COL5A2	string_interaction
COL1A1	COL1A2	intact
COL1A1	COL3A1	string_interaction
COL1A1	COL5A1	intact, string_interaction
COL1A1	COL5A2	string_interaction
COL1A2	COL5A1	intact
COL3A1	COL5A1	string_interaction
COL3A1	COL5A2	string_interaction
COL5A1	COL5A2	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL1A1	P02452	14
COL3A1	P02461	11
KCNT1	Q5JUK3	6
COL1A2	P08123	5
DNAJB6	O75190	4
COL5A1	P20908	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CASD1	Q96PB1	87.87
AEBP1	Q8IUX7	67.99
COL5A2	P05997	53.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 9 evidence-associated genes (6 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 6 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	5	475.8×	2e-12	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Syndecan interactions	5	352.5×	5e-12	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
MET activates PTK2 signaling	5	317.2×	6e-12	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Collagen chain trimerization	5	216.3×	4e-11	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Developmental Lineage of Pancreatic Ductal Cells	5	190.3×	5e-11	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Assembly of collagen fibrils and other multimeric structures	5	167.0×	9e-11	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Collagen degradation	5	146.4×	2e-10	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Collagen biosynthesis and modifying enzymes	5	142.0×	2e-10	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Non-integrin membrane-ECM interactions	5	128.6×	2e-10	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
ECM proteoglycans	5	125.2×	2e-10	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Integrin cell surface interactions	5	112.0×	4e-10	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
Scavenging by Class A Receptors	3	300.5×	2e-07	COL1A1, COL1A2, COL3A1
Defective VWF binding to collagen type I	2	1268.9×	2e-06	COL1A1, COL1A2
Signaling by PDGF	3	126.9×	3e-06	COL5A1, COL3A1, COL5A2
NCAM1 interactions	3	124.1×	3e-06	COL5A1, COL3A1, COL5A2
Enhanced cleavage of VWF variant by ADAMTS13	2	951.7×	3e-06	COL1A1, COL1A2
Defective VWF cleavage by ADAMTS13 variant	2	951.7×	3e-06	COL1A1, COL1A2
Enhanced binding of GP1BA variant to VWF multimer:collagen	2	543.8×	9e-06	COL1A1, COL1A2
Defective binding of VWF variant to GPIb:IX:V	2	543.8×	9e-06	COL1A1, COL1A2
GP1b-IX-V activation signalling	2	317.2×	3e-05	COL1A1, COL1A2
Anchoring fibril formation	2	253.8×	4e-05	COL1A1, COL1A2
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	3	43.6×	5e-05	COL1A1, COL1A2, COL3A1
Platelet Adhesion to exposed collagen	2	223.9×	5e-05	COL1A1, COL1A2
Crosslinking of collagen fibrils	2	190.3×	6e-05	COL1A1, COL1A2
Attachment of bacteria to epithelial cells	2	165.5×	8e-05	COL5A1, COL5A2
Platelet Aggregation (Plug Formation)	2	146.4×	1e-04	COL1A1, COL1A2
GPVI-mediated activation cascade	2	102.9×	2e-04	COL1A1, COL1A2
Cell surface interactions at the vascular wall	2	31.7×	0.002	COL1A1, COL1A2
RUNX2 regulates osteoblast differentiation	1	76.1×	0.016	COL1A1
Attenuation phase	1	68.0×	0.017	DNAJB6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
collagen fibril organization	5	124.8×	2e-08	COL5A1, COL1A1, COL1A2, COL3A1, COL5A2
cellular response to amino acid stimulus	4	136.2×	7e-07	COL1A1, COL1A2, COL3A1, COL5A2
negative regulation of endodermal cell differentiation	2	1872.4×	9e-06	COL5A1, COL5A2
skin development	3	147.8×	2e-05	COL5A1, COL3A1, COL5A2
eye morphogenesis	2	936.2×	3e-05	COL5A1, COL5A2
blood vessel development	3	124.8×	3e-05	COL5A1, COL1A1, COL1A2
skin morphogenesis	2	312.1×	3e-04	COL1A1, COL1A2
collagen biosynthetic process	2	234.1×	4e-04	COL5A1, COL1A1
supramolecular fiber organization	2	234.1×	4e-04	COL5A1, COL3A1
skeletal system development	3	41.9×	4e-04	COL1A1, COL1A2, COL5A2
protein localization to nucleus	2	78.0×	0.003	DNAJB6, COL1A1
integrin biosynthetic process	1	1872.4×	0.004	COL5A1
protein heterotrimerization	1	1872.4×	0.004	COL1A2
cellular response to vitamin E	1	1872.4×	0.004	COL1A1
cellular response to fluoride	1	936.2×	0.008	COL1A1
transforming growth factor beta1 production	1	624.1×	0.008	COL3A1
tooth mineralization	1	624.1×	0.008	COL1A1
limb joint morphogenesis	1	624.1×	0.008	COL3A1
syncytiotrophoblast cell differentiation involved in labyrinthine layer development	1	624.1×	0.008	DNAJB6
chorion development	1	624.1×	0.008	DNAJB6
regulation of collagen fibril organization	1	624.1×	0.008	AEBP1
transforming growth factor beta receptor signaling pathway	2	35.3×	0.008	COL1A2, COL3A1
tendon development	1	468.1×	0.009	COL5A1
endochondral bone morphogenesis	1	468.1×	0.009	COL3A1
aorta smooth muscle tissue morphogenesis	1	468.1×	0.009	COL3A1
cellular response to acetaldehyde	1	374.5×	0.011	COL1A1
intramembranous ossification	1	312.1×	0.013	COL1A1
cartilage development involved in endochondral bone morphogenesis	1	267.5×	0.014	COL1A1
bone trabecula formation	1	234.1×	0.015	COL1A1
chorio-allantoic fusion	1	234.1×	0.015	DNAJB6

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8

Druggability breadth: 7 of 9 evidence-associated genes (78%) 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
KCNT1	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNT1	2	4
COL5A1	0	0
DNAJB6	0	0
CASD1	0	0
COL1A1	0	0
COL1A2	0	0
COL3A1	0	0
COL5A2	0	0
AEBP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KCNT1	24	Binding:24
COL1A1	8	Binding:8
COL1A2	4	Functional:4
DNAJB6	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CASD1	2.3.1.45	N-acetylneuraminate 9-O-acetyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
BEPRIDIL	4	KCNT1
QUINIDINE	4	KCNT1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KCNT1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	CASD1, AEBP1
E	Difficult family or no structure, no drug	6	COL5A1, DNAJB6, COL1A1, COL1A2, COL3A1, COL5A2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL5A1	0	—
DNAJB6	2	—
CASD1	0	—
COL1A1	8	—
COL1A2	4	—
COL3A1	0	—
COL5A2	0	—
AEBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.