Osteogenesis imperfecta type 1

Summary

Osteogenesis imperfecta type 1 (MONDO:0008146) is a disease with 9 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Sweden) [Orphanet-validated]
• Cohort genes: 9
• ClinVar variants: 4,628

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	5.16	Sweden	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	osteogenesis imperfecta type 1
Mondo ID	MONDO:0008146
OMIM	166200
Orphanet	216796
DOID	DOID:0110334
ICD-11	1897905410
NCIT	C99003
SNOMED CT	385482004
UMLS	C0023931
MedGen	9799
GARD	0008694
Is cancer (heuristic)	no

Also known as: Adair-Dighton syndrome · classic non-deforming OI with blue sclerae · COL1A1-related osteogenesis imperfecta · mild osteogenesis imperfecta · non-deforming osteogenesis imperfecta · OI type 1 · OI1 · osteogenesis imperfecta type 1 · osteogenesis imperfecta type I · Van der Hoeve syndrome

Data availability: 4,628 ClinVar variants · 4 GenCC gene-disease records · 10 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › osteogenesis imperfecta › osteogenesis imperfecta and a reduction of bone mineral density. › osteogenesis imperfecta type 1

Related subtypes (32): Cole-Carpenter syndrome 1, calvarial doughnut lesions-bone fragility syndrome, osteogenesis imperfecta type 2, osteogenesis imperfecta type 4, gnathodiaphyseal dysplasia, geroderma osteodysplastica, osteogenesis imperfecta type 3, osteogenesis imperfecta type 9, osteoporosis-pseudoglioma syndrome, Wiedemann-Rautenstrauch syndrome, spondylo-ocular syndrome, Bruck syndrome 2, osteogenesis imperfecta type 7, osteogenesis imperfecta type 8, osteogenesis imperfecta type 5, osteogenesis imperfecta type 11, autosomal recessive cutis laxa type 2B, osteogenesis imperfecta type 10, osteogenesis imperfecta type 12, osteogenesis imperfecta type 6, short stature-optic atrophy-Pelger-Huët anomaly syndrome, osteogenesis imperfecta type 14, osteogenesis imperfecta type 15, osteogenesis imperfecta type 16, Cole-Carpenter syndrome 2, Singleton-Merten syndrome 2, osteogenesis imperfecta type 17, autosomal recessive cutis laxa type 2A, Ehlers-Danlos syndrome, spondylodysplastic type, 1, Singleton-Merten syndrome 1, osteogenesis imperfecta, type 18, osteogenesis imperfecta, type 19

Subtypes (1): osteogenesis imperfecta with opalescent teeth, blue sclerae and wormian bones but without fractures

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:

184 pathogenic, 174 uncertain significance, 118 likely benign, 62 conflicting classifications of pathogenicity, 28 pathogenic/likely pathogenic, 19 likely pathogenic, 8 benign/likely benign, 7 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069647	NM_000088.4(COL1A1):c.2678G>C (p.Gly893Ala)	COL1A1	Pathogenic	criteria provided, single submitter
1069928	NM_000088.4(COL1A1):c.2235+1G>C	COL1A1	Pathogenic	criteria provided, single submitter
1069954	NM_000088.4(COL1A1):c.394_395del (p.Asp132fs)	COL1A1	Pathogenic	criteria provided, single submitter
1070187	NM_000088.4(COL1A1):c.3589_3590del (p.Asp1197fs)	COL1A1	Pathogenic	criteria provided, single submitter
1070188	NM_000088.4(COL1A1):c.3569G>A (p.Gly1190Asp)	COL1A1	Pathogenic	criteria provided, single submitter
1070189	NM_000088.4(COL1A1):c.3531+1G>C	COL1A1	Pathogenic	criteria provided, single submitter
1070241	NM_000088.4(COL1A1):c.3020del (p.Gly1007fs)	COL1A1	Pathogenic	criteria provided, single submitter
1070818	NM_000088.4(COL1A1):c.3051del (p.Pro1018fs)	COL1A1	Pathogenic	criteria provided, single submitter
1070914	NM_000088.4(COL1A1):c.2907_2908delinsAT (p.Arg970Ter)	COL1A1	Pathogenic	criteria provided, single submitter
1071489	NM_000088.4(COL1A1):c.814G>A (p.Gly272Ser)	COL1A1	Pathogenic	criteria provided, single submitter
1072196	NM_000088.4(COL1A1):c.2585_2586del (p.Lys862fs)	COL1A1	Pathogenic	criteria provided, single submitter
1072429	NM_000088.4(COL1A1):c.2101G>A (p.Gly701Ser)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072430	NM_000088.4(COL1A1):c.1981C>T (p.Gln661Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1072431	NM_000088.4(COL1A1):c.1886del (p.Gly629fs)	COL1A1	Pathogenic	criteria provided, single submitter
1072588	NM_000088.4(COL1A1):c.958-1G>A	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073168	NM_000088.4(COL1A1):c.595C>T (p.Gln199Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1073803	NM_000088.4(COL1A1):c.3061_3068del (p.Glu1021fs)	COL1A1	Pathogenic	criteria provided, single submitter
1074006	NM_000088.4(COL1A1):c.3910C>T (p.Gln1304Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1074007	NM_000088.4(COL1A1):c.3385C>T (p.Gln1129Ter)	COL1A1	Pathogenic	criteria provided, single submitter
1074064	NM_000088.4(COL1A1):c.1797del (p.Val600fs)	COL1A1	Pathogenic	criteria provided, single submitter
1074183	NM_000088.4(COL1A1):c.1821del (p.Gly608fs)	COL1A1	Pathogenic	criteria provided, single submitter
1074312	NM_000088.4(COL1A1):c.1614+1G>A	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1074344	NM_000088.4(COL1A1):c.1804G>T (p.Gly602Ter)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1074370	NM_000088.4(COL1A1):c.642+2T>A	COL1A1	Pathogenic	criteria provided, single submitter
1074716	NM_000088.4(COL1A1):c.1451del (p.Pro484fs)	COL1A1	Pathogenic	criteria provided, single submitter
1074717	NM_000088.4(COL1A1):c.1003G>A (p.Gly335Ser)	COL1A1	Pathogenic	criteria provided, single submitter
1074867	NM_000088.4(COL1A1):c.3649del (p.Arg1217fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1075011	NM_000088.4(COL1A1):c.2584A>T (p.Lys862Ter)	COL1A1	Pathogenic	criteria provided, single submitter
1075143	NM_000088.4(COL1A1):c.976G>C (p.Gly326Arg)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076006	NM_000088.4(COL1A1):c.288del (p.Asp97fs)	COL1A1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 56 · Orphanet: 22 · 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	osteogenesis imperfecta type 4	20
COL1A2	Definitive	Autosomal dominant	osteogenesis imperfecta	21
P4HB	Supportive	Autosomal dominant	osteogenesis imperfecta type 1	7
SEC24D	Supportive	Autosomal dominant	osteogenesis imperfecta type 1	8

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
SEC24D	Orphanet:2050	Cole-Carpenter syndrome
SEC24D	Orphanet:216796	Osteogenesis imperfecta type 1
P4HB	Orphanet:2050	Cole-Carpenter syndrome
P4HB	Orphanet:216796	Osteogenesis imperfecta type 1

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
COL1A1	HGNC:2197	ENSG00000108821	P02452	Collagen alpha-1(I) chain	gencc,clinvar
COL1A2	HGNC:2198	ENSG00000164692	P08123	Collagen alpha-2(I) chain	gencc,clinvar
SEC24D	HGNC:10706	ENSG00000150961	O94855	Protein transport protein Sec24D	gencc
P4HB	HGNC:8548	ENSG00000185624	P07237	Protein disulfide-isomerase	gencc
CASD1	HGNC:16014	ENSG00000127995	Q96PB1	N-acetylneuraminate (7)9-O-acetyltransferase	clinvar
ACSF2	HGNC:26101	ENSG00000167107	Q96CM8	Medium-chain acyl-CoA ligase ACSF2, mitochondrial	clinvar
SAMD14	HGNC:27312	ENSG00000167100	Q8IZD0	Sterile alpha motif domain-containing protein 14	clinvar
ABCC3	HGNC:54	ENSG00000108846	O15438	ATP-binding cassette sub-family C member 3	clinvar
PDK2	HGNC:8810	ENSG00000005882	Q15119	[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial	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).
SEC24D	Protein transport protein Sec24D	Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).
P4HB	Protein disulfide-isomerase	This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds.
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.
ACSF2	Medium-chain acyl-CoA ligase ACSF2, mitochondrial	Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA.
ABCC3	ATP-binding cassette sub-family C member 3	ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes.
PDK2	[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial	Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2.

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.44

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	8.6×	0.423
Enzyme (other)	2	2.7×	0.423
Kinase	1	3.1×	0.469
Transcription factor	1	0.9×	0.847
Other/Unknown	4	0.8×	0.847

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
SEC24D	Transcription factor	no		Znf_Sec23_Sec24, Sec23/24_trunk_dom, Sec23/24_helical_dom
P4HB	Enzyme (other)	yes	5.3.4.1	PDI_thioredoxin-like_dom, Prot_disulphide_isomerase, Thioredoxin_domain
CASD1	Enzyme (other)	yes	2.3.1.45	Cas1_AcylTrans_dom, Cyclin-like_sf, NXPE4_C
ACSF2	Other/Unknown	no		AMP-dep_synth/lig_dom, AMP-binding_CS, AMP-bd_C
SAMD14	Other/Unknown	no		SAM, SAM/pointed_sf, Neurabin-like
ABCC3	Transporter	yes	7.6.2.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP
PDK2	Kinase	yes	2.7.11.2	HATPase_dom, His_kinase_dom, BCDHK/PDK_N

Expression context

Cohort genes with no expression data: 0.

8 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
stromal cell of endometrium	4
periodontal ligament	2
skin of hip	2
jejunal mucosa	2
right adrenal gland cortex	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
islet of Langerhans	1
parotid gland	1
Ammon’s horn	1
adrenal tissue	1
postcentral gyrus	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1
cerebellar cortex	1
pancreatic ductal cell	1
right adrenal gland	1
hindlimb stylopod muscle	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
SEC24D	263	ubiquitous	marker	stromal cell of endometrium, jejunal mucosa, islet of Langerhans
P4HB	293	ubiquitous	marker	stromal cell of endometrium, parotid gland, jejunal mucosa
CASD1	278	ubiquitous	marker	adrenal tissue, postcentral gyrus, Ammon’s horn
ACSF2	244	ubiquitous	marker	right lobe of thyroid gland, right adrenal gland cortex, left lobe of thyroid gland
SAMD14	213	ubiquitous	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ABCC3	231	ubiquitous	marker	pancreatic ductal cell, right adrenal gland, right adrenal gland cortex
PDK2	272	ubiquitous	marker	hindlimb stylopod muscle, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL1A1	5,341
P4HB	5,111
PDK2	3,247
ACSF2	2,853
ABCC3	1,937
SEC24D	1,176
SAMD14	520
CASD1	426
COL1A2	179

Intra-cohort edges

A	B	Sources
COL1A1	COL1A2	intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDK2	Q15119	38
COL1A1	P02452	14
P4HB	P07237	14
SEC24D	O94855	6
COL1A2	P08123	5
ABCC3	O15438	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACSF2	Q96CM8	89.40
CASD1	Q96PB1	87.87
SAMD14	Q8IZD0	60.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 81. Enrichment computed across 9 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective VWF binding to collagen type I	2	1087.6×	5e-05	COL1A1, COL1A2
Enhanced cleavage of VWF variant by ADAMTS13	2	815.7×	5e-05	COL1A1, COL1A2
Defective VWF cleavage by ADAMTS13 variant	2	815.7×	5e-05	COL1A1, COL1A2
Enhanced binding of GP1BA variant to VWF multimer:collagen	2	466.1×	9e-05	COL1A1, COL1A2
Defective binding of VWF variant to GPIb:IX:V	2	466.1×	9e-05	COL1A1, COL1A2
Collagen biosynthesis and modifying enzymes	3	73.0×	9e-05	COL1A1, COL1A2, P4HB
GP1b-IX-V activation signalling	2	271.9×	2e-04	COL1A1, COL1A2
Anchoring fibril formation	2	217.5×	3e-04	COL1A1, COL1A2
Platelet Adhesion to exposed collagen	2	191.9×	4e-04	COL1A1, COL1A2
Scavenging by Class A Receptors	2	171.7×	4e-04	COL1A1, COL1A2
Fibronectin matrix formation	2	163.1×	4e-04	COL1A1, COL1A2
Crosslinking of collagen fibrils	2	163.1×	4e-04	COL1A1, COL1A2
Platelet Aggregation (Plug Formation)	2	125.5×	6e-04	COL1A1, COL1A2
Syndecan interactions	2	120.8×	6e-04	COL1A1, COL1A2
MET activates PTK2 signaling	2	108.8×	8e-04	COL1A1, COL1A2
GPVI-mediated activation cascade	2	88.2×	0.001	COL1A1, COL1A2
Collagen chain trimerization	2	74.2×	0.001	COL1A1, COL1A2
Developmental Lineage of Pancreatic Ductal Cells	2	65.3×	0.002	COL1A1, COL1A2
Assembly of collagen fibrils and other multimeric structures	2	57.2×	0.002	COL1A1, COL1A2
Collagen degradation	2	50.2×	0.003	COL1A1, COL1A2
Non-integrin membrane-ECM interactions	2	44.1×	0.003	COL1A1, COL1A2
ECM proteoglycans	2	42.9×	0.003	COL1A1, COL1A2
Metabolism of lipids	3	13.5×	0.004	SEC24D, ACSF2, ABCC3
Metabolism of steroids	2	39.3×	0.004	SEC24D, ABCC3
Integrin cell surface interactions	2	38.4×	0.004	COL1A1, COL1A2
Cell surface interactions at the vascular wall	2	27.2×	0.007	COL1A1, COL1A2
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	2	24.9×	0.008	COL1A1, COL1A2
VLDL assembly	1	326.3×	0.009	P4HB
LDL remodeling	1	271.9×	0.010	P4HB
NFE2L2 regulating MDR associated enzymes	1	203.9×	0.013	ABCC3

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
skin morphogenesis	2	312.1×	0.002	COL1A1, COL1A2
protein heterotrimerization	1	1872.4×	0.010	COL1A2
cellular response to vitamin E	1	1872.4×	0.010	COL1A1
blood vessel development	2	83.2×	0.010	COL1A1, COL1A2
cellular response to amino acid stimulus	2	68.1×	0.010	COL1A1, COL1A2
collagen fibril organization	2	49.9×	0.011	COL1A1, COL1A2
peptidyl-proline hydroxylation to 4-hydroxy-L-proline	1	936.2×	0.011	P4HB
regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	936.2×	0.011	P4HB
cellular response to fluoride	1	936.2×	0.011	COL1A1
tooth mineralization	1	624.1×	0.015	COL1A1
regulation of ketone metabolic process	1	468.1×	0.015	PDK2
endoplasmic reticulum to Golgi vesicle-mediated transport	2	30.2×	0.015	SEC24D, P4HB
skeletal system development	2	27.9×	0.015	COL1A1, COL1A2
cellular response to acetaldehyde	1	374.5×	0.017	COL1A1
intramembranous ossification	1	312.1×	0.017	COL1A1
regulation of pyruvate decarboxylation to acetyl-CoA	1	312.1×	0.017	PDK2
interleukin-23-mediated signaling pathway	1	312.1×	0.017	P4HB
cartilage development involved in endochondral bone morphogenesis	1	267.5×	0.018	COL1A1
leukotriene transport	1	267.5×	0.018	ABCC3
cellular response to nutrient	1	234.1×	0.019	PDK2
bone trabecula formation	1	234.1×	0.019	COL1A1
interleukin-12-mediated signaling pathway	1	208.1×	0.020	P4HB
insulin processing	1	187.2×	0.021	P4HB
regulation of pH	1	156.0×	0.023	PDK2
protein folding in endoplasmic reticulum	1	156.0×	0.023	P4HB
collagen-activated tyrosine kinase receptor signaling pathway	1	144.0×	0.023	COL1A1
cellular response to interleukin-7	1	144.0×	0.023	P4HB
positive regulation of viral entry into host cell	1	133.8×	0.023	P4HB
regulation of gluconeogenesis	1	124.8×	0.023	PDK2
regulation of calcium-mediated signaling	1	124.8×	0.023	PDK2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 3 · Undrugged: 6

Druggability breadth: 5 of 9 evidence-associated genes (56%) 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
ABCC3	TELMISARTAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC3	43	4
P4HB	1	2
PDK2	1	2
COL1A1	0	0
COL1A2	0	0
SEC24D	0	0
CASD1	0	0
ACSF2	0	0
SAMD14	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TELMISARTAN	4	ABCC3
VALRUBICIN	4	ABCC3
SAQUINAVIR	4	ABCC3
OLMESARTAN MEDOXOMIL	4	ABCC3
LOTEPREDNOL ETABONATE	4	ABCC3
TEMSIROLIMUS	4	ABCC3
REPAGLINIDE	4	ABCC3
CLOFAZIMINE	4	ABCC3
TOLCAPONE	4	ABCC3
BUDESONIDE	4	ABCC3
GLIMEPIRIDE	4	ABCC3
IRBESARTAN	4	ABCC3
CYCLOSPORINE	4	ABCC3
RIFAXIMIN	4	ABCC3
RITONAVIR	4	ABCC3
RIFAPENTINE	4	ABCC3
ROSUVASTATIN CALCIUM	4	ABCC3
EVEROLIMUS	4	ABCC3
RACECADOTRIL	4	ABCC3
FLUVASTATIN	4	ABCC3
SITAXENTAN	4	ABCC3
ETRAVIRINE	4	ABCC3
ETHAMBUTOL HYDROCHLORIDE	4	ABCC3
RIFAMPIN	4	ABCC3
ATORVASTATIN CALCIUM	4	ABCC3
TROGLITAZONE	4	ABCC3
SULFASALAZINE	4	ABCC3
TENIPOSIDE	4	ABCC3
ETHACRYNIC ACID	4	ABCC3
GLYBURIDE	4	ABCC3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
PDK2	98	Binding:97, Functional:1
P4HB	69	Binding:64, Functional:5
ABCC3	37	Binding:21, ADMET:16
COL1A1	8	Binding:8
COL1A2	4	Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
P4HB	5.3.4.1	protein disulfide-isomerase
CASD1	2.3.1.45	N-acetylneuraminate 9-O-acetyltransferase
ABCC3	7.6.2.3	ABC-type glutathione-S-conjugate transporter
PDK2	2.7.11.2	[pyruvate dehydrogenase (acetyl-transferring)] kinase

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

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)
TELMISARTAN	4	ABCC3
VALRUBICIN	4	ABCC3
SAQUINAVIR	4	ABCC3
OLMESARTAN MEDOXOMIL	4	ABCC3
LOTEPREDNOL ETABONATE	4	ABCC3
TEMSIROLIMUS	4	ABCC3
REPAGLINIDE	4	ABCC3
CLOFAZIMINE	4	ABCC3
TOLCAPONE	4	ABCC3
BUDESONIDE	4	ABCC3
GLIMEPIRIDE	4	ABCC3
IRBESARTAN	4	ABCC3
CYCLOSPORINE	4	ABCC3
RIFAXIMIN	4	ABCC3
RITONAVIR	4	ABCC3
RIFAPENTINE	4	ABCC3
ROSUVASTATIN CALCIUM	4	ABCC3
EVEROLIMUS	4	ABCC3
RACECADOTRIL	4	ABCC3
FLUVASTATIN	4	ABCC3
SITAXENTAN	4	ABCC3
ETRAVIRINE	4	ABCC3
ETHAMBUTOL HYDROCHLORIDE	4	ABCC3
RIFAMPIN	4	ABCC3
ATORVASTATIN CALCIUM	4	ABCC3
TROGLITAZONE	4	ABCC3
SULFASALAZINE	4	ABCC3
TENIPOSIDE	4	ABCC3
ETHACRYNIC ACID	4	ABCC3
GLYBURIDE	4	ABCC3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC3
B	Phased (≥1) drug, not yet approved	2	P4HB, PDK2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CASD1
E	Difficult family or no structure, no drug	5	COL1A1, COL1A2, SEC24D, ACSF2, SAMD14

Undrugged target profiles

6 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	—
SEC24D	0	—
CASD1	0	—
ACSF2	0	—
SAMD14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.