Hypertrophic cardiomyopathy 26

Summary

Hypertrophic cardiomyopathy 26 (MONDO:0014883) is a disease caused by FLNC (GenCC Strong), with 7 cohort genes.

At a glance

• Causal gene: FLNC (GenCC Strong)
• Cohort genes: 7
• ClinVar variants: 5,242

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 26
Mondo ID	MONDO:0014883
OMIM	617047
DOID	DOID:0110327
UMLS	C4310749
MedGen	934716
GARD	0025029
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 26 · cardiomyopathy, familial hypertrophic, type 26 · cardiomyopathy, familial restrictive 5 · CMH26 · FLNC hypertrophic cardiomyopathy · hypertrophic cardiomyopathy caused by mutation in FLNC · hypertrophic cardiomyopathy type 26

Data availability: 5,242 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › hypertrophic cardiomyopathy › familial hypertrophic cardiomyopathy › hypertrophic cardiomyopathy 26

Related subtypes (39): hypertrophic cardiomyopathy 2, hypertrophic cardiomyopathy 3, hypertrophic cardiomyopathy 4, Beckwith-Wiedemann syndrome, myotonic dystrophy type 1, hypertrophic cardiomyopathy 1, very long chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency, 46,XY complete gonadal dysgenesis, hypertrophic cardiomyopathy 6, dilated cardiomyopathy 1C, hypertrophic cardiomyopathy 25, hypertrophic cardiomyopathy 8, hypertrophic cardiomyopathy 10, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, cardiomyopathy-hypotonia-lactic acidosis syndrome, hypertrophic cardiomyopathy 11, hypertrophic cardiomyopathy 12, hypertrophic cardiomyopathy 13, hypertrophic cardiomyopathy 14, hypertrophic cardiomyopathy 15, hypertrophic cardiomyopathy 7, hypertrophic cardiomyopathy 9, hypertrophic cardiomyopathy 16, hypertrophic cardiomyopathy 17, hypertrophic cardiomyopathy 18, hypertrophic cardiomyopathy 19, hypertrophic cardiomyopathy 20, hypertrophic cardiomyopathy 21, dilated cardiomyopathy 1KK, Noonan syndrome and Noonan-related syndrome, long chain acyl-CoA dehydrogenase deficiency, cardiomyopathy, familial hypertrophic, 28, cardiomyopathy, familial hypertrophic 27, cardiomyopathy, familial hypertrophic, 23, with or without ventricular noncompaction, cardiomyopathy, familial restrictive, 5, cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, cardiomyopathy, familial hypertrophic, 30, atrial, cardiomyopathy, familial hypertrophic, 31

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:

267 likely benign, 204 uncertain significance, 46 conflicting classifications of pathogenicity, 39 pathogenic, 24 benign, 10 benign/likely benign, 7 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067540	NM_001458.5(FLNC):c.5199+1G>T	FLNC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068545	NM_001458.5(FLNC):c.6955del (p.Ala2319fs)	FLNC	Pathogenic	criteria provided, single submitter
1068586	NM_001458.5(FLNC):c.4432C>T (p.Gln1478Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1068631	NM_001458.5(FLNC):c.1205del (p.Thr402fs)	FLNC	Pathogenic	criteria provided, single submitter
1068840	NM_001458.5(FLNC):c.1991_1994del (p.Asp664fs)	FLNC	Pathogenic	criteria provided, single submitter
1068841	NM_001458.5(FLNC):c.3702del (p.Val1235fs)	FLNC	Pathogenic	criteria provided, single submitter
1069362	NM_001458.5(FLNC):c.1914C>G (p.Tyr638Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1069877	NM_001458.5(FLNC):c.2604del (p.Ser868fs)	FLNC	Pathogenic	criteria provided, single submitter
1070209	NM_001458.5(FLNC):c.4718T>A (p.Leu1573Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1070523	NM_001458.5(FLNC):c.5520T>A (p.Tyr1840Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1070569	NM_001458.5(FLNC):c.6802G>T (p.Glu2268Ter)	FLNC	Pathogenic	criteria provided, single submitter
1070575	NM_001458.5(FLNC):c.4755del (p.Lys1586fs)	FLNC	Pathogenic	criteria provided, single submitter
1071490	NM_001458.5(FLNC):c.1670del (p.Pro557fs)	FLNC	Pathogenic	criteria provided, single submitter
1071491	NM_001458.5(FLNC):c.5733dup (p.Gly1912fs)	FLNC	Pathogenic	criteria provided, single submitter
1071678	NM_001458.5(FLNC):c.5569_5578del (p.Ile1857fs)	FLNC	Pathogenic	criteria provided, single submitter
1071863	NC_000007.13:g.(?128470682)(128498587_?)del	FLNC	Pathogenic	criteria provided, single submitter
1071864	NC_000007.13:g.(?128469483)(128500328_?)del	FLNC	Pathogenic	criteria provided, single submitter
1071931	NM_001458.5(FLNC):c.261del (p.Pro88fs)	FLNC	Pathogenic	criteria provided, single submitter
1072180	NM_001458.5(FLNC):c.2499C>A (p.Tyr833Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1072269	NM_001458.5(FLNC):c.3070C>T (p.Gln1024Ter)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1072270	NM_001458.5(FLNC):c.6240_6259del (p.Pro2081fs)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1072629	NM_001458.5(FLNC):c.181C>T (p.Gln61Ter)	FLNC	Pathogenic	criteria provided, single submitter
1073366	NM_001458.5(FLNC):c.4946del (p.Gly1649fs)	FLNC	Pathogenic	criteria provided, multiple submitters, no conflicts
1073410	NM_001458.5(FLNC):c.156dup (p.Val53fs)	FLNC	Pathogenic	criteria provided, single submitter
1074200	NM_001458.5(FLNC):c.5557del (p.Tyr1853fs)	FLNC	Pathogenic	criteria provided, single submitter
1074377	NM_001458.5(FLNC):c.563del (p.Gly188fs)	FLNC	Pathogenic	criteria provided, single submitter
1074392	NM_001458.5(FLNC):c.2548C>T (p.Gln850Ter)	FLNC	Pathogenic	criteria provided, single submitter
1074694	NM_001458.5(FLNC):c.146_147insT (p.Leu50fs)	FLNC	Pathogenic	criteria provided, single submitter
1074904	NM_001458.5(FLNC):c.1893G>A (p.Trp631Ter)	FLNC	Pathogenic	criteria provided, single submitter
1075295	NM_001458.5(FLNC):c.4275dup (p.Arg1426fs)	FLNC	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 38 · 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
FLNC	Definitive	Autosomal dominant	dilated cardiomyopathy	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FLNC	Orphanet:171445	Muscle filaminopathy
FLNC	Orphanet:63273	FLNC-related handgrip and calf weakness-distal myopathy
FLNC	Orphanet:75249	Familial isolated restrictive cardiomyopathy
TNPO3	Orphanet:186	Primary biliary cholangitis
TNPO3	Orphanet:55595	TNP03-related limb-girdle muscular dystrophy D2
DOLK	Orphanet:154	Familial isolated dilated cardiomyopathy
DOLK	Orphanet:91131	DK1-CDG
HBB	Orphanet:2132	Hemoglobin C disease
HBB	Orphanet:2133	Hemoglobin E disease
HBB	Orphanet:231214	Beta-thalassemia major
HBB	Orphanet:231222	Beta-thalassemia intermedia
HBB	Orphanet:231226	Unstable beta globin chain variant disease
HBB	Orphanet:231237	Delta-beta-thalassemia
HBB	Orphanet:231242	Hemoglobin C-beta-thalassemia syndrome
HBB	Orphanet:231249	Hemoglobin E-beta-thalassemia syndrome
HBB	Orphanet:232	Sickle cell anemia
HBB	Orphanet:247511	Autosomal dominant secondary polycythemia
HBB	Orphanet:251365	Sickle cell S-C disease
HBB	Orphanet:251370	Sickle cell S-D Punjab disease
HBB	Orphanet:251375	Sickle cell S-E disease
HBB	Orphanet:251380	Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
HBB	Orphanet:330041	Hemoglobin M disease
HBB	Orphanet:46532	Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
HBB	Orphanet:695140	Sickle cell-beta zero-thalassemia
HBB	Orphanet:695147	Sickle cell-beta plus-thalassemia
HBB	Orphanet:699822	Sickle cell S-Lepore disease
HBB	Orphanet:700090	Sickle cell S-O Arab disease
HBB	Orphanet:700107	Sickle cell S-other specified hemoglobin variant
HBB	Orphanet:700111	Homozygous hemoglobin O Arab disease
HBB	Orphanet:715125	Hemoglobin E-beta-thalassemia intermedia
HBB	Orphanet:715128	Hemoglobin E-beta-thalassemia major
HBB	Orphanet:715135	Hemoglobin Lepore-beta-thalassemia intermedia
HBB	Orphanet:715140	Hemoglobin Lepore-beta-thalassemia major
HBB	Orphanet:715143	Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBB	Orphanet:715157	Low oxygen affinity beta chain hemoglobin disease
HBB	Orphanet:90039	Hemoglobin D disease
KCNH2	Orphanet:101016	Romano-Ward syndrome
KCNH2	Orphanet:51083	Congenital short QT syndrome

Cohort genes → proteins

7 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FLNC	HGNC:3756	ENSG00000128591	Q14315	Filamin-C	gencc,clinvar
ATP6V1F	HGNC:16832	ENSG00000128524	Q16864	V-type proton ATPase subunit F	clinvar
TNPO3	HGNC:17103	ENSG00000064419	Q9Y5L0	Transportin-3	clinvar
DOLK	HGNC:23406	ENSG00000175283	Q9UPQ8	Dolichol kinase	clinvar
HBB	HGNC:4827	ENSG00000244734	P68871	Hemoglobin subunit beta	clinvar
FLNC-AS1	HGNC:53474	ENSG00000242902		FLNC antisense RNA 1	clinvar
KCNH2	HGNC:6251	ENSG00000055118	Q12809	Voltage-gated inwardly rectifying potassium channel KCNH2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FLNC	Filamin-C	Muscle-specific filamin, which plays a central role in sarcomere assembly and organization.
ATP6V1F	V-type proton ATPase subunit F	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.
TNPO3	Transportin-3	Importin, which transports target proteins into the nucleus.
DOLK	Dolichol kinase	Catalyzes CTP-mediated phosphorylation of dolichol, the terminal step in de novo dolichyl monophosphate (Dol-P) biosynthesis.
HBB	Hemoglobin subunit beta	Involved in oxygen transport from the lung to the various peripheral tissues.
KCNH2	Voltage-gated inwardly rectifying potassium channel KCNH2	Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.43

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	15.9×	0.244
Antibody/Immunoglobulin	1	4.2×	0.302
Kinase	1	4.0×	0.302
Other/Unknown	4	1.0×	0.626

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FLNC	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
ATP6V1F	Other/Unknown	no		ATPase_V1-cplx_fsu_euk, ATPase_V1-cplx_f_g_su, ATPase_V1_fsu_sf
TNPO3	Other/Unknown	no		ARM-like, Exportin-1/Importin-b-like, ARM-type_fold
DOLK	Kinase	yes	2.7.1.108	Polypren_kinase
HBB	Other/Unknown	no		Globin, Hemoglobin_b, Globin-like_sf
FLNC-AS1	Other/Unknown	no
KCNH2	Ion channel	yes		PAS, cNMP-bd_dom, PAS-assoc_C

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	2
apex of heart	2
gastrocnemius	1
tibialis anterior	1
left testis	1
prefrontal cortex	1
right testis	1
medial globus pallidus	1
secondary oocyte	1
tendon of biceps brachii	1
endometrium epithelium	1
primordial germ cell in gonad	1
stromal cell of endometrium	1
monocyte	1
trabecular bone tissue	1
vena cava	1
muscle of leg	1
cardiac atrium	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FLNC	255	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, tibialis anterior
ATP6V1F	294	ubiquitous	marker	prefrontal cortex, left testis, right testis
TNPO3	299	ubiquitous	marker	secondary oocyte, tendon of biceps brachii, medial globus pallidus
DOLK	253	ubiquitous	marker	primordial germ cell in gonad, stromal cell of endometrium, endometrium epithelium
HBB	284	broad	marker	monocyte, trabecular bone tissue, vena cava
FLNC-AS1	114		yes	hindlimb stylopod muscle, apex of heart, muscle of leg
KCNH2	211	broad	marker	apex of heart, right atrium auricular region, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNC	3,174
TNPO3	2,970
ATP6V1F	2,214
KCNH2	1,932
DOLK	1,476
HBB	454
FLNC-AS1	0

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HBB	P68871	350
KCNH2	Q12809	24
FLNC	Q14315	14
ATP6V1F	Q16864	8
TNPO3	Q9Y5L0	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DOLK	Q9UPQ8	90.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 7 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
Defective DOLK causes DOLK-CDG	1	2284.0×	0.011	DOLK
Heme assimilation	1	761.3×	0.016	HBB
Synthesis of dolichyl-phosphate	1	326.3×	0.020	DOLK
Erythrocytes take up oxygen and release carbon dioxide	1	253.8×	0.020	HBB
Phase 3 - rapid repolarisation	1	228.4×	0.020	KCNH2
Erythrocytes take up carbon dioxide and release oxygen	1	175.7×	0.020	HBB
Scavenging of heme from plasma	1	175.7×	0.020	HBB
Cell-extracellular matrix interactions	1	134.3×	0.021	FLNC
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	134.3×	0.021	ATP6V1F
Chaperone Mediated Autophagy	1	99.3×	0.025	HBB
Insulin receptor recycling	1	76.1×	0.027	ATP6V1F
Transferrin endocytosis and recycling	1	73.7×	0.027	ATP6V1F
ROS and RNS production in phagocytes	1	67.2×	0.027	ATP6V1F
Late endosomal microautophagy	1	65.3×	0.027	HBB
Voltage gated Potassium channels	1	48.6×	0.034	KCNH2
Heme signaling	1	43.1×	0.036	HBB
Amino acids regulate mTORC1	1	40.1×	0.036	ATP6V1F
Cytoprotection by HMOX1	1	36.8×	0.037	HBB
Potassium Channels	1	26.9×	0.048	KCNH2
Cardiac conduction	1	21.8×	0.056	KCNH2
Ion channel transport	1	19.2×	0.061	ATP6V1F
Muscle contraction	1	15.4×	0.072	KCNH2
Factors involved in megakaryocyte development and platelet production	1	13.3×	0.079	HBB
Neuronal System	1	8.8×	0.112	KCNH2
Neutrophil degranulation	1	4.6×	0.199	HBB

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of heart rate by hormone	1	1404.3×	0.013	KCNH2
nitric oxide transport	1	561.7×	0.013	HBB
negative regulation of potassium ion export across plasma membrane	1	401.2×	0.013	KCNH2
dolichyl monophosphate biosynthetic process	1	312.1×	0.013	DOLK
cellular oxidant detoxification	1	312.1×	0.013	HBB
Golgi lumen acidification	1	280.9×	0.013	ATP6V1F
renal absorption	1	280.9×	0.013	HBB
membrane depolarization during action potential	1	280.9×	0.013	KCNH2
membrane repolarization during action potential	1	280.9×	0.013	KCNH2
membrane repolarization during cardiac muscle cell action potential	1	280.9×	0.013	KCNH2
membrane repolarization during ventricular cardiac muscle cell action potential	1	280.9×	0.013	KCNH2
negative regulation of potassium ion transmembrane transport	1	234.1×	0.013	KCNH2
carbon dioxide transport	1	216.1×	0.013	HBB
regulation of membrane repolarization	1	216.1×	0.013	KCNH2
membrane repolarization	1	216.1×	0.013	KCNH2
endosomal lumen acidification	1	200.6×	0.013	ATP6V1F
intracellular pH reduction	1	200.6×	0.013	ATP6V1F
oxygen transport	1	175.5×	0.013	HBB
potassium ion export across plasma membrane	1	175.5×	0.013	KCNH2
ventricular cardiac muscle cell action potential	1	165.2×	0.013	KCNH2
positive regulation of potassium ion transmembrane transport	1	165.2×	0.013	KCNH2
synaptic vesicle lumen acidification	1	156.0×	0.013	ATP6V1F
regulation of ventricular cardiac muscle cell membrane repolarization	1	140.4×	0.014	KCNH2
potassium ion homeostasis	1	127.7×	0.015	KCNH2
vacuolar acidification	1	122.1×	0.015	ATP6V1F
lysosomal lumen acidification	1	112.3×	0.015	ATP6V1F
hydrogen peroxide catabolic process	1	112.3×	0.015	HBB
blood vessel diameter maintenance	1	104.0×	0.015	HBB
regulation of potassium ion transmembrane transport	1	104.0×	0.015	KCNH2
erythrocyte development	1	87.8×	0.017	HBB

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 3 of 7 evidence-associated genes (43%) 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
HBB	CANDESARTAN CILEXETIL
KCNH2	CETIRIZINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNH2	706	4
HBB	23	4
FLNC	0	0
ATP6V1F	0	0
TNPO3	0	0
DOLK	0	0
FLNC-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANDESARTAN CILEXETIL	4	HBB
MECHLORETHAMINE HYDROCHLORIDE	4	HBB
PHENAZOPYRIDINE HYDROCHLORIDE	4	HBB
MERCAPTOPURINE ANHYDROUS	4	HBB
AZACITIDINE	4	HBB
AZATHIOPRINE	4	HBB
TOPOTECAN HYDROCHLORIDE	4	HBB
ACYCLOVIR	4	HBB
FLUOROURACIL	4	HBB
RAUWOLFIA SERPENTINA	4	HBB
HYDROQUINONE	4	HBB
MENADIONE	4	HBB
THIOTEPA	4	HBB, KCNH2
THIOGUANINE	4	HBB
RESERPINE	4	HBB, KCNH2
CETIRIZINE	4	KCNH2
BEPRIDIL	4	KCNH2
BEXAROTENE	4	KCNH2
CLOTRIMAZOLE	4	KCNH2
MORICIZINE	4	KCNH2
PROPIVERINE	4	KCNH2
SUVOREXANT	4	KCNH2
ACETOPHENAZINE	4	KCNH2
DIBUCAINE	4	KCNH2
MESORIDAZINE	4	KCNH2
NIRAPARIB	4	KCNH2
BUPIVACAINE	4	KCNH2
IMIPRAMINE	4	KCNH2
BIPERIDEN	4	KCNH2
EPINASTINE	4	KCNH2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KCNH2	4,851	Binding:3558, Toxicity:1071, Functional:169, ADMET:53
HBB	68	Binding:50, Functional:18
TNPO3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DOLK	2.7.1.108	dolichol kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KCNH2	4,851

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
CANDESARTAN CILEXETIL	4	HBB
MECHLORETHAMINE HYDROCHLORIDE	4	HBB
PHENAZOPYRIDINE HYDROCHLORIDE	4	HBB
MERCAPTOPURINE ANHYDROUS	4	HBB
AZACITIDINE	4	HBB
AZATHIOPRINE	4	HBB
TOPOTECAN HYDROCHLORIDE	4	HBB
ACYCLOVIR	4	HBB
FLUOROURACIL	4	HBB
RAUWOLFIA SERPENTINA	4	HBB
HYDROQUINONE	4	HBB
MENADIONE	4	HBB
THIOTEPA	4	HBB, KCNH2
THIOGUANINE	4	HBB
RESERPINE	4	HBB, KCNH2
CETIRIZINE	4	KCNH2
BEPRIDIL	4	KCNH2
BEXAROTENE	4	KCNH2
CLOTRIMAZOLE	4	KCNH2
MORICIZINE	4	KCNH2
PROPIVERINE	4	KCNH2
SUVOREXANT	4	KCNH2
ACETOPHENAZINE	4	KCNH2
DIBUCAINE	4	KCNH2
MESORIDAZINE	4	KCNH2
NIRAPARIB	4	KCNH2
BUPIVACAINE	4	KCNH2
IMIPRAMINE	4	KCNH2
BIPERIDEN	4	KCNH2
EPINASTINE	4	KCNH2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	HBB, KCNH2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	FLNC
D	Druggable family + AlphaFold only, no drug	1	DOLK
E	Difficult family or no structure, no drug	3	ATP6V1F, TNPO3, FLNC-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FLNC	0	—
ATP6V1F	0	—
TNPO3	1	—
DOLK	0	—
FLNC-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.