Hypertrophic cardiomyopathy 1
diseaseOn this page
Also known as cardiomyopathy, familial hypertrophic, 1cardiomyopathy, familial hypertrophic, Autosomal dominant, Digenic dominantcardiomyopathy, familial hypertrophic, type 1cardiomyopathy, hypertrophic, 1, Autosomal dominant, Digenic dominantcardiomyopathy, hypertrophic, 1, digenic, Autosomal dominant, Digenic dominantCMH1hypertrophic cardiomyopathy caused by mutation in MYH7hypertrophic cardiomyopathy type 1MYH7 hypertrophic cardiomyopathy
Summary
Hypertrophic cardiomyopathy 1 (MONDO:0008647) is a disease caused by MYH7 (GenCC Definitive), with 30 cohort genes. The dominant Reactome pathway is Striated Muscle Contraction (9 cohort genes).
At a glance
- Causal gene: MYH7 (GenCC Definitive)
- Cohort genes: 30
- ClinVar variants: 1,477
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hypertrophic cardiomyopathy 1 |
| Mondo ID | MONDO:0008647 |
| OMIM | 192600 |
| DOID | DOID:0110307 |
| UMLS | C3495498 |
| MedGen | 501195 |
| GARD | 0024636 |
| Is cancer (heuristic) | no |
Also known as: cardiomyopathy, familial hypertrophic, 1 · cardiomyopathy, familial hypertrophic, Autosomal dominant, Digenic dominant · cardiomyopathy, familial hypertrophic, type 1 · cardiomyopathy, hypertrophic, 1, Autosomal dominant, Digenic dominant · cardiomyopathy, hypertrophic, 1, digenic, Autosomal dominant, Digenic dominant · CMH1 · hypertrophic cardiomyopathy 1 · hypertrophic cardiomyopathy caused by mutation in MYH7 · hypertrophic cardiomyopathy type 1 · MYH7 hypertrophic cardiomyopathy
Data availability: 1,477 ClinVar variants · 6 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 1
Related subtypes (39): hypertrophic cardiomyopathy 2, hypertrophic cardiomyopathy 3, hypertrophic cardiomyopathy 4, Beckwith-Wiedemann syndrome, myotonic dystrophy type 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, hypertrophic cardiomyopathy 26, 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:
262 uncertain significance, 123 likely benign, 96 conflicting classifications of pathogenicity, 35 pathogenic, 28 likely pathogenic, 27 pathogenic/likely pathogenic, 19 benign/likely benign, 10 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 14100 | NM_000257.4(MYH7):c.2333A>G (p.Asp778Gly) | LOC126861898 | Pathogenic | criteria provided, single submitter |
| 14120 | NM_000257.4(MYH7):c.2609G>A (p.Arg870His) | LOC126861898 | Pathogenic | reviewed by expert panel |
| 164324 | NM_000257.4(MYH7):c.2572C>T (p.Arg858Cys) | LOC126861898 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 164337 | NM_000257.4(MYH7):c.2302G>A (p.Gly768Arg) | LOC126861898 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 181196 | NM_000257.4(MYH7):c.2605C>T (p.Arg869Cys) | LOC126861898 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1801829 | NM_006767.4(LZTR1):c.736C>T (p.Gln246Ter) | LZTR1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 164284 | NM_000257.4(MYH7):c.4498C>T (p.Arg1500Trp) | MHRT | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 181010 | NC_000011.10:g.47332705G>C | MYBPC3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 181076 | NM_000256.3(MYBPC3):c.1838dup (p.Asp613fs) | MYBPC3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 217827 | NM_000256.3(MYBPC3):c.1302C>A (p.Tyr434Ter) | MYBPC3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 217835 | NM_000256.3(MYBPC3):c.1359del (p.Val454fs) | MYBPC3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 217836 | NM_000256.3(MYBPC3):c.3712_3713del (p.Leu1238fs) | MYBPC3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 217832 | NM_002471.4(MYH6):c.3193dup (p.Gln1065fs) | MYH6 | Pathogenic | criteria provided, single submitter |
| 132925 | NM_000257.4(MYH7):c.1573G>A (p.Glu525Lys) | MYH7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14087 | NM_000257.4(MYH7):c.1208G>A (p.Arg403Gln) | MYH7 | Pathogenic | reviewed by expert panel |
| 14088 | NM_000257.4(MYH7):c.746G>A (p.Arg249Gln) | MYH7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14089 | NM_000257.4(MYH7):c.1357C>T (p.Arg453Cys) | MYH7 | Pathogenic | reviewed by expert panel |
| 14090 | NM_000257.4(MYH7):c.1750G>C (p.Gly584Arg) | MYH7 | Pathogenic | reviewed by expert panel |
| 14091 | NM_000257.4(MYH7):c.1816G>A (p.Val606Met) | MYH7 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14092 | NM_000257.4(MYH7):c.2770G>A (p.Glu924Lys) | MYH7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14095 | NM_000257.4(MYH7):c.2167C>T (p.Arg723Cys) | MYH7 | Pathogenic | reviewed by expert panel |
| 14096 | nsv513807 | MYH7 | Pathogenic | no assertion criteria provided |
| 14097 | NM_000257.4(MYH7):c.2722C>G (p.Leu908Val) | MYH7 | Pathogenic | reviewed by expert panel |
| 14098 | NM_000257.4(MYH7):c.2221G>C (p.Gly741Arg) | MYH7 | Pathogenic | reviewed by expert panel |
| 14099 | NM_000257.4(MYH7):c.767G>A (p.Gly256Glu) | MYH7 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14101 | NM_000257.4(MYH7):c.1208G>T (p.Arg403Leu) | MYH7 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14102 | NM_000257.4(MYH7):c.1207C>T (p.Arg403Trp) | MYH7 | Pathogenic | reviewed by expert panel |
| 14103 | NM_000257.4(MYH7):c.1538T>G (p.Phe513Cys) | MYH7 | Pathogenic | no assertion criteria provided |
| 14104 | NM_000257.4(MYH7):c.2155C>T (p.Arg719Trp) | MYH7 | Pathogenic | reviewed by expert panel |
| 14105 | NM_000257.4(MYH7):c.2146G>A (p.Gly716Arg) | MYH7 | Pathogenic | reviewed by expert panel |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 24 · Orphanet: 87 · 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 |
|---|---|---|---|---|
| MYH7 | Definitive | Autosomal dominant | hypertrophic cardiomyopathy 1 | 20 |
| MYLK2 | Limited | Autosomal dominant | hypertrophic cardiomyopathy 1 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MYH7 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| MYH7 | Orphanet:1880 | Ebstein malformation of the tricuspid valve |
| MYH7 | Orphanet:324604 | Classic multiminicore myopathy |
| MYH7 | Orphanet:54260 | Left ventricular noncompaction |
| MYH7 | Orphanet:59135 | Laing distal myopathy |
| MYH7 | Orphanet:636965 | Autosomal dominant myosin storage myopathy |
| MYH7 | Orphanet:636970 | Autosomal recessive myosin storage myopathy |
| SGCD | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| SGCD | Orphanet:219 | Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 |
| TCAP | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TCAP | Orphanet:34514 | Telethonin-related limb-girdle muscular dystrophy R7 |
| TNNI3 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TNNI3 | Orphanet:75249 | Familial isolated restrictive cardiomyopathy |
| TNNT2 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TNNT2 | Orphanet:54260 | Left ventricular noncompaction |
| TNNT2 | Orphanet:75249 | Familial isolated restrictive cardiomyopathy |
| TPM1 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TPM1 | Orphanet:54260 | Left ventricular noncompaction |
| CACNA1C | Orphanet:101016 | Romano-Ward syndrome |
| CACNA1C | Orphanet:130 | Brugada syndrome |
| CACNA1C | Orphanet:528084 | Non-specific syndromic intellectual disability |
| CACNA1C | Orphanet:595098 | Timothy syndrome type 1 |
| CACNA1C | Orphanet:595105 | Timothy syndrome type 2 |
| CACNA1C | Orphanet:595109 | Atypical Timothy syndrome |
| JPH2 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| CAV3 | Orphanet:101016 | Romano-Ward syndrome |
| CAV3 | Orphanet:206599 | Isolated asymptomatic elevation of creatine phosphokinase |
| CAV3 | Orphanet:488650 | Distal myopathy, Tateyama type |
| CAV3 | Orphanet:97238 | Rippling muscle disease |
| LDB3 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| LDB3 | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| LDB3 | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| LDB3 | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| LDB3 | Orphanet:54260 | Left ventricular noncompaction |
| LDB3 | Orphanet:98912 | Late-onset distal myopathy, Markesbery-Griggs type |
| OBSCN | Orphanet:99845 | Genetic recurrent myoglobinuria |
| ANKRD1 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| MYH7B | Orphanet:54260 | Left ventricular noncompaction |
| ACTN2 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| ACTN2 | Orphanet:708129 | Autosomal recessive ACTN2-related distal myopathy |
| ACTN2 | Orphanet:708133 | Autosomal dominant ACTN2-related distal myopathy |
| MYPN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| MYPN | Orphanet:171439 | Childhood-onset nemaline myopathy |
| MYPN | Orphanet:171881 | Cap myopathy |
| MYPN | Orphanet:75249 | Familial isolated restrictive cardiomyopathy |
| CSRP3 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| NEXN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| GLA | Orphanet:324 | Fabry disease |
| LAMA4 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| LMNA | Orphanet:154 | Familial isolated dilated cardiomyopathy |
Cohort genes → proteins
30 cohort genes, 29 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 30 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| MYLK2 | HGNC:16243 | ENSG00000101306 | Q9H1R3 | Myosin light chain kinase 2, skeletal/cardiac muscle | gencc,clinvar |
| MYH7 | HGNC:7577 | ENSG00000092054 | P12883 | Myosin-7 | gencc,clinvar |
| SGCD | HGNC:10807 | ENSG00000170624 | Q92629 | Delta-sarcoglycan | clinvar |
| TCAP | HGNC:11610 | ENSG00000173991 | O15273 | Telethonin | clinvar |
| TNNI3 | HGNC:11947 | ENSG00000129991 | P19429 | Troponin I, cardiac muscle | clinvar |
| TNNT2 | HGNC:11949 | ENSG00000118194 | P45379 | Troponin T, cardiac muscle | clinvar |
| TPM1 | HGNC:12010 | ENSG00000140416 | P09493 | Tropomyosin alpha-1 chain | clinvar |
| CACNA1C | HGNC:1390 | ENSG00000151067 | Q13936 | Voltage-dependent L-type calcium channel subunit alpha-1C | clinvar |
| JPH2 | HGNC:14202 | ENSG00000149596 | Q9BR39 | Junctophilin-2 | clinvar |
| CAV3 | HGNC:1529 | ENSG00000182533 | P56539 | Caveolin-3 | clinvar |
| LDB3 | HGNC:15710 | ENSG00000122367 | O75112 | LIM domain-binding protein 3 | clinvar |
| OBSCN | HGNC:15719 | ENSG00000154358 | Q5VST9 | Obscurin | clinvar |
| ANKRD1 | HGNC:15819 | ENSG00000148677 | Q15327 | Ankyrin repeat domain-containing protein 1 | clinvar |
| MYH7B | HGNC:15906 | ENSG00000078814 | A7E2Y1 | Myosin-7B | clinvar |
| ACTN2 | HGNC:164 | ENSG00000077522 | P35609 | Alpha-actinin-2 | clinvar |
| MYPN | HGNC:23246 | ENSG00000138347 | Q86TC9 | Myopalladin | clinvar |
| CSRP3 | HGNC:2472 | ENSG00000129170 | P50461 | Cysteine and glycine-rich protein 3 | clinvar |
| NEXN | HGNC:29557 | ENSG00000162614 | Q0ZGT2 | Nexilin | clinvar |
| GLA | HGNC:4296 | ENSG00000102393 | P06280 | Alpha-galactosidase A | clinvar |
| MHRT | HGNC:51291 | myosin heavy chain associated RNA transcript | clinvar | ||
| LAMA4 | HGNC:6484 | ENSG00000112769 | Q16363 | Laminin subunit alpha-4 | clinvar |
| LMNA | HGNC:6636 | ENSG00000160789 | P02545 | Prelamin-A/C | clinvar |
| LZTR1 | HGNC:6742 | ENSG00000099949 | Q8N653 | Leucine-zipper-like transcriptional regulator 1 | clinvar |
| MYBPC3 | HGNC:7551 | ENSG00000134571 | Q14896 | Myosin-binding protein C, cardiac-type | clinvar |
| MYH6 | HGNC:7576 | ENSG00000197616 | P13533 | Myosin-6 | clinvar |
| MYL2 | HGNC:7583 | ENSG00000111245 | P10916 | Myosin regulatory light chain 2, ventricular/cardiac muscle isoform | clinvar |
| MYL3 | HGNC:7584 | ENSG00000160808 | P08590 | Myosin light chain 3 | clinvar |
| OXTR | HGNC:8529 | ENSG00000180914 | P30559 | Oxytocin receptor | clinvar |
| PRKAG2 | HGNC:9386 | ENSG00000106617 | Q9UGJ0 | 5’-AMP-activated protein kinase subunit gamma-2 | clinvar |
| RAF1 | HGNC:9829 | ENSG00000132155 | P04049 | RAF proto-oncogene serine/threonine-protein kinase | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MYLK2 | Myosin light chain kinase 2, skeletal/cardiac muscle | Implicated in the level of global muscle contraction and cardiac function. |
| MYH7 | Myosin-7 | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. |
| SGCD | Delta-sarcoglycan | Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix. |
| TCAP | Telethonin | Muscle assembly regulating factor. |
| TNNI3 | Troponin I, cardiac muscle | Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. |
| TNNT2 | Troponin T, cardiac muscle | Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. |
| TPM1 | Tropomyosin alpha-1 chain | Binds to actin filaments in muscle and non-muscle cells. |
| CACNA1C | Voltage-dependent L-type calcium channel subunit alpha-1C | Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. |
| JPH2 | Junctophilin-2 | Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes. |
| CAV3 | Caveolin-3 | May act as a scaffolding protein within caveolar membranes. |
| LDB3 | LIM domain-binding protein 3 | May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton. |
| OBSCN | Obscurin | Structural component of striated muscles which plays a role in myofibrillogenesis. |
| ANKRD1 | Ankyrin repeat domain-containing protein 1 | May play an important role in endothelial cell activation. |
| MYH7B | Myosin-7B | Involved in muscle contraction. |
| ACTN2 | Alpha-actinin-2 | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. |
| MYPN | Myopalladin | Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines. |
| CSRP3 | Cysteine and glycine-rich protein 3 | Positive regulator of myogenesis. |
| NEXN | Nexilin | Involved in regulating cell migration through association with the actin cytoskeleton. |
| GLA | Alpha-galactosidase A | Catalyzes the hydrolysis of glycosphingolipids and participates in their degradation in the lysosome. |
| LAMA4 | Laminin subunit alpha-4 | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. |
| LMNA | Prelamin-A/C | Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. |
| LZTR1 | Leucine-zipper-like transcriptional regulator 1 | Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates ubiquitination of Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS). |
| MYBPC3 | Myosin-binding protein C, cardiac-type | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. |
| MYH6 | Myosin-6 | Muscle contraction. |
| MYL2 | Myosin regulatory light chain 2, ventricular/cardiac muscle isoform | Contractile protein that plays a role in heart development and function. |
| MYL3 | Myosin light chain 3 | Regulatory light chain of myosin. |
| OXTR | Oxytocin receptor | Receptor for oxytocin. |
| PRKAG2 | 5’-AMP-activated protein kinase subunit gamma-2 | AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. |
| RAF1 | RAF proto-oncogene serine/threonine-protein kinase | Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including prolifer… |
Protein-family classification
Druggable: 9 · Difficult: 6 · Unknown: 15 · Druggable fraction: 0.3
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 |
|---|---|---|---|
| Antibody/Immunoglobulin | 3 | 2.9× | 0.247 |
| Kinase | 3 | 2.8× | 0.247 |
| Scaffold/PPI | 4 | 2.3× | 0.247 |
| Ion channel | 1 | 3.7× | 0.474 |
| Other/Unknown | 15 | 0.9× | 0.927 |
| GPCR | 1 | 0.8× | 0.927 |
| Transcription factor | 2 | 0.6× | 0.927 |
| Enzyme (other) | 1 | 0.4× | 0.927 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| MYLK2 | Kinase | yes | 2.7.11.18 | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| MYH7 | Scaffold/PPI | no | IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail | |
| SGCD | Other/Unknown | no | Sarcoglycan, Sarcoglycan_gamma/delta/zeta | |
| TCAP | Other/Unknown | no | Telethonin, Titin-like_dom_sf | |
| TNNI3 | Other/Unknown | no | Troponin, Troponin-I_N, Troponin_sf | |
| TNNT2 | Other/Unknown | no | Troponin, TNNT, Troponin_sf | |
| TPM1 | Other/Unknown | no | Tropomyosin | |
| CACNA1C | Ion channel | yes | VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu | |
| JPH2 | Other/Unknown | no | MORN, Junctophilin | |
| CAV3 | Other/Unknown | no | Caveolin, Caveolin_CS | |
| LDB3 | Transcription factor | no | PDZ, Znf_LIM, Zasp-like_motif | |
| OBSCN | Kinase | yes | IQ_motif_EF-hand-BS, DH_dom, Prot_kinase_dom | |
| ANKRD1 | Scaffold/PPI | no | Ankyrin_rpt, Ankyrin_rpt-contain_sf | |
| MYH7B | Scaffold/PPI | no | Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin | |
| ACTN2 | Other/Unknown | no | Actinin_actin-bd_CS, CH_dom, Spectrin_repeat | |
| MYPN | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, Ig-like_dom | |
| CSRP3 | Transcription factor | no | Znf_LIM | |
| NEXN | Antibody/Immunoglobulin | yes | Ig_sub, Ig-like_dom, Ig_I-set | |
| GLA | Enzyme (other) | yes | 3.2.1.22 | Glyco_hydro_27/36_CS, Glyco_hydro_27, Glyco_hydro_b |
| MHRT | Other/Unknown | no | ||
| LAMA4 | Other/Unknown | no | EGF, Laminin_G, LE_dom | |
| LMNA | Other/Unknown | no | Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf | |
| LZTR1 | Other/Unknown | no | BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf | |
| MYBPC3 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| MYH6 | Scaffold/PPI | no | Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin | |
| MYL2 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS | |
| MYL3 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, CALM/Myosin/TropC-like | |
| OXTR | GPCR | yes | GPCR_Rhodpsn, Vasoprsn_rcpt, Oxytocn_rcpt | |
| PRKAG2 | Other/Unknown | no | CBS_dom, CBS_dom_sf, AMPK_gamma/SDS23_families | |
| RAF1 | Kinase | yes | 2.7.10.2 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE |
Expression context
Cohort genes with no expression data: 1.
23 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) | 29 |
| unknown | 1 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| apex of heart | 12 |
| hindlimb stylopod muscle | 10 |
| skeletal muscle tissue of rectus abdominis | 7 |
| left ventricle myocardium | 6 |
| heart right ventricle | 5 |
| right atrium auricular region | 5 |
| cardiac atrium | 5 |
| gastrocnemius | 4 |
| skeletal muscle tissue of biceps brachii | 3 |
| myocardium | 2 |
| vastus lateralis | 2 |
| cardiac muscle of right atrium | 2 |
| muscle layer of sigmoid colon | 1 |
| right coronary artery | 1 |
| tibialis anterior | 1 |
| triceps brachii | 1 |
| heart left ventricle | 1 |
| monocyte | 1 |
| mononuclear cell | 1 |
| pancreatic ductal cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MYLK2 | 148 | tissue_specific | yes | hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, gastrocnemius |
| MYH7 | 167 | tissue_specific | marker | apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii |
| SGCD | 247 | broad | marker | left ventricle myocardium, skeletal muscle tissue of rectus abdominis, heart right ventricle |
| TCAP | 213 | tissue_specific | marker | apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis |
| TNNI3 | 169 | broad | marker | apex of heart, left ventricle myocardium, right atrium auricular region |
| TNNT2 | 154 | broad | marker | apex of heart, right atrium auricular region, cardiac atrium |
| TPM1 | 305 | ubiquitous | marker | left ventricle myocardium, heart right ventricle, myocardium |
| CACNA1C | 134 | broad | marker | apex of heart, right coronary artery, muscle layer of sigmoid colon |
| JPH2 | 173 | broad | yes | left ventricle myocardium, skeletal muscle tissue of rectus abdominis, tibialis anterior |
| CAV3 | 157 | tissue_specific | yes | hindlimb stylopod muscle, vastus lateralis, triceps brachii |
| LDB3 | 247 | broad | marker | skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart |
| OBSCN | 197 | ubiquitous | marker | hindlimb stylopod muscle, apex of heart, gastrocnemius |
| ANKRD1 | 155 | ubiquitous | marker | apex of heart, right atrium auricular region, cardiac atrium |
| MYH7B | 195 | broad | yes | apex of heart, hindlimb stylopod muscle, heart left ventricle |
| ACTN2 | 226 | broad | marker | skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle |
| MYPN | 116 | broad | marker | hindlimb stylopod muscle, gastrocnemius, vastus lateralis |
| CSRP3 | 173 | tissue_specific | marker | skeletal muscle tissue of rectus abdominis, heart right ventricle, left ventricle myocardium |
| NEXN | 229 | ubiquitous | marker | left ventricle myocardium, skeletal muscle tissue of rectus abdominis, myocardium |
| GLA | 263 | ubiquitous | marker | pancreatic ductal cell, monocyte, mononuclear cell |
| MHRT | ||||
| LAMA4 | 268 | ubiquitous | marker | lower esophagus muscularis layer, lower esophagus, nerve |
| LMNA | 295 | ubiquitous | marker | nipple, mucosa of stomach, skin of abdomen |
| LZTR1 | 134 | ubiquitous | marker | sural nerve, pituitary gland, adenohypophysis |
| MYBPC3 | 149 | tissue_specific | marker | apex of heart, right atrium auricular region, cardiac atrium |
| MYH6 | 154 | tissue_specific | yes | cardiac muscle of right atrium, cardiac atrium, vena cava |
| MYL2 | 179 | tissue_specific | marker | heart right ventricle, diaphragm, apex of heart |
| MYL3 | 198 | broad | marker | apex of heart, heart right ventricle, hindlimb stylopod muscle |
| OXTR | 204 | broad | yes | decidua, bronchial epithelial cell, epithelium of mammary gland |
| PRKAG2 | 258 | ubiquitous | marker | right atrium auricular region, cardiac atrium, cardiac muscle of right atrium |
| RAF1 | 299 | ubiquitous | marker | gastrocnemius, muscle of leg, ventricular zone |
Protein interactions among cohort
Intra-cohort edges: 88.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LMNA | 7,173 |
| RAF1 | 6,574 |
| TPM1 | 3,514 |
| PRKAG2 | 3,212 |
| CACNA1C | 3,145 |
| MYH6 | 3,119 |
| MYL2 | 3,119 |
| ACTN2 | 2,781 |
| MYH7 | 2,744 |
| LAMA4 | 2,688 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ACTN2 | CACNA1C | biogrid_interaction |
| ACTN2 | CSRP3 | intact, string_interaction |
| ACTN2 | LDB3 | biogrid_interaction, intact, string_interaction |
| ACTN2 | MYH6 | biogrid_interaction, string_interaction |
| ACTN2 | MYH7 | biogrid_interaction, string_interaction |
| ACTN2 | MYPN | biogrid_interaction, string_interaction |
| ACTN2 | NEXN | string_interaction |
| ACTN2 | TCAP | string_interaction |
| ACTN2 | TNNT2 | string_interaction |
| ACTN2 | TPM1 | biogrid_interaction, string_interaction |
| ANKRD1 | CSRP3 | string_interaction |
| ANKRD1 | MYPN | biogrid_interaction, string_interaction |
| ANKRD1 | TCAP | string_interaction |
| CACNA1C | CAV3 | string_interaction |
| CACNA1C | JPH2 | string_interaction |
| CAV3 | JPH2 | string_interaction |
| CSRP3 | LDB3 | string_interaction |
| CSRP3 | MYBPC3 | string_interaction |
| CSRP3 | MYH7 | string_interaction |
| CSRP3 | MYL2 | string_interaction |
| CSRP3 | MYL3 | string_interaction |
| CSRP3 | MYLK2 | string_interaction |
| CSRP3 | MYPN | string_interaction |
| CSRP3 | NEXN | string_interaction |
| CSRP3 | PRKAG2 | string_interaction |
| CSRP3 | TCAP | intact, string_interaction |
| CSRP3 | TNNI3 | string_interaction |
| CSRP3 | TNNT2 | string_interaction |
| CSRP3 | TPM1 | string_interaction |
| JPH2 | TCAP | string_interaction |
| LDB3 | MYBPC3 | string_interaction |
| LDB3 | MYH7 | string_interaction |
| LDB3 | MYPN | intact |
| LDB3 | NEXN | string_interaction |
| LDB3 | TCAP | string_interaction |
| LDB3 | TNNT2 | string_interaction |
| LMNA | SGCD | string_interaction |
| LZTR1 | MYH6 | intact |
| MYBPC3 | MYH6 | string_interaction |
| MYBPC3 | MYH7 | intact, string_interaction |
| MYBPC3 | MYL2 | string_interaction |
| MYBPC3 | MYL3 | string_interaction |
| MYBPC3 | MYLK2 | string_interaction |
| MYBPC3 | PRKAG2 | string_interaction |
| MYBPC3 | TCAP | string_interaction |
| MYBPC3 | TNNI3 | string_interaction |
| MYBPC3 | TNNT2 | string_interaction |
| MYBPC3 | TPM1 | string_interaction |
| MYH6 | MYL2 | string_interaction |
| MYH6 | MYL3 | string_interaction |
Structural data
PDB: 20 · AlphaFold-only: 9 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| RAF1 | P04049 | 76 |
| MYH7 | P12883 | 43 |
| TNNI3 | P19429 | 39 |
| CACNA1C | Q13936 | 33 |
| GLA | P06280 | 31 |
| LMNA | P02545 | 28 |
| TNNT2 | P45379 | 25 |
| OBSCN | Q5VST9 | 25 |
| MYBPC3 | Q14896 | 17 |
| ACTN2 | P35609 | 16 |
| TPM1 | P09493 | 14 |
| LZTR1 | Q8N653 | 3 |
| MYL2 | P10916 | 3 |
| MYL3 | P08590 | 3 |
| OXTR | P30559 | 3 |
| MYLK2 | Q9H1R3 | 2 |
| TCAP | O15273 | 2 |
| JPH2 | Q9BR39 | 2 |
| LDB3 | O75112 | 2 |
| CSRP3 | P50461 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CAV3 | P56539 | 88.54 |
| ANKRD1 | Q15327 | 82.64 |
| SGCD | Q92629 | 81.43 |
| MYH6 | P13533 | 74.91 |
| MYH7B | A7E2Y1 | 73.79 |
| LAMA4 | Q16363 | 73.75 |
| NEXN | Q0ZGT2 | 70.78 |
| PRKAG2 | Q9UGJ0 | 67.24 |
| MYPN | Q86TC9 | 52.71 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 118. Enrichment computed across 30 evidence-associated genes (20 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 20 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Striated Muscle Contraction | 9 | 138.9× | 3e-16 | TCAP, TNNI3, TNNT2, TPM1, ACTN2, MYBPC3, MYH6, MYL2 (+1 more) |
| Muscle contraction | 8 | 30.9× | 4e-09 | TCAP, CACNA1C, CAV3, ACTN2, MYBPC3, MYH6, MYL2, MYL3 |
| Formation of the dystrophin-glycoprotein complex (DGC) | 2 | 30.9× | 0.074 | SGCD, LAMA4 |
| Smooth Muscle Contraction | 2 | 26.6× | 0.074 | TPM1, CAV3 |
| Breakdown of the nuclear lamina | 1 | 190.3× | 0.079 | LMNA |
| Post NMDA receptor activation events | 2 | 20.4× | 0.079 | ACTN2, PRKAG2 |
| Activation of NMDA receptors and postsynaptic events | 2 | 18.4× | 0.079 | ACTN2, PRKAG2 |
| Integration of energy metabolism | 2 | 17.6× | 0.079 | CACNA1C, PRKAG2 |
| Signaling by BRAF and RAF1 fusions | 2 | 17.0× | 0.079 | LMNA, RAF1 |
| Non-integrin membrane-ECM interactions | 2 | 15.4× | 0.086 | SGCD, LAMA4 |
| Vasopressin-like receptors | 1 | 95.2× | 0.103 | OXTR |
| Negative feedback regulation of MAPK pathway | 1 | 95.2× | 0.103 | RAF1 |
| AMPK inhibits chREBP transcriptional activation activity | 1 | 71.4× | 0.103 | PRKAG2 |
| SHOC2 M1731 mutant abolishes MRAS complex function | 1 | 71.4× | 0.103 | RAF1 |
| Gain-of-function MRAS complexes activate RAF signaling | 1 | 71.4× | 0.103 | RAF1 |
| IFNG signaling activates MAPKs | 1 | 71.4× | 0.103 | RAF1 |
| Lipophagy | 1 | 63.4× | 0.108 | PRKAG2 |
| Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 1 | 57.1× | 0.108 | PRKAG2 |
| Neurotransmitter receptors and postsynaptic signal transmission | 2 | 10.0× | 0.108 | ACTN2, PRKAG2 |
| GP1b-IX-V activation signalling | 1 | 47.6× | 0.122 | RAF1 |
| CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 1 | 43.9× | 0.122 | ACTN2 |
| Carnitine shuttle | 1 | 38.1× | 0.122 | PRKAG2 |
| Depolymerization of the Nuclear Lamina | 1 | 38.1× | 0.122 | LMNA |
| Phase 2 - plateau phase | 1 | 38.1× | 0.122 | CACNA1C |
| Rap1 signalling | 1 | 35.7× | 0.122 | RAF1 |
| Transmission across Chemical Synapses | 2 | 7.6× | 0.122 | ACTN2, PRKAG2 |
| Metabolism of lipids | 3 | 4.7× | 0.122 | ANKRD1, GLA, PRKAG2 |
| Initiation of Nuclear Envelope (NE) Reformation | 1 | 30.1× | 0.125 | LMNA |
| MET promotes cell motility | 1 | 30.1× | 0.125 | LAMA4 |
| Ras activation upon Ca2+ influx through NMDA receptor | 1 | 28.6× | 0.125 | ACTN2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 29 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| cardiac muscle contraction | 11 | 152.2× | 5e-20 | MYLK2, MYH7, TCAP, TNNI3, TNNT2, TPM1, CSRP3, MYBPC3 (+3 more) |
| sarcomere organization | 11 | 145.3× | 5e-20 | TCAP, TNNT2, TPM1, LDB3, OBSCN, ANKRD1, ACTN2, MYPN (+3 more) |
| ventricular cardiac muscle tissue morphogenesis | 8 | 193.7× | 2e-15 | MYH7, TNNI3, TNNT2, TPM1, MYBPC3, MYH6, MYL2, MYL3 |
| muscle filament sliding | 6 | 217.9× | 8e-12 | MYH7, TCAP, TNNI3, TNNT2, TPM1, MYH6 |
| regulation of the force of heart contraction | 5 | 170.9× | 4e-09 | MYH7, CSRP3, MYH6, MYL2, MYL3 |
| cardiac muscle cell development | 5 | 107.6× | 4e-08 | SGCD, TCAP, CAV3, ACTN2, MYH6 |
| detection of muscle stretch | 3 | 249.0× | 6e-06 | TCAP, CAV3, CSRP3 |
| regulation of striated muscle contraction | 3 | 217.9× | 9e-06 | MYBPC3, MYL2, MYL3 |
| regulation of heart contraction | 4 | 68.4× | 1e-05 | TNNT2, TPM1, CAV3, MYH6 |
| cardiac muscle hypertrophy | 3 | 174.3× | 2e-05 | TCAP, CAV3, CSRP3 |
| cardiac muscle tissue morphogenesis | 3 | 145.3× | 3e-05 | MYLK2, TCAP, ANKRD1 |
| cardiac myofibril assembly | 3 | 134.1× | 3e-05 | TCAP, CSRP3, MYL2 |
| adult heart development | 3 | 124.5× | 4e-05 | MYH7, TCAP, MYH6 |
| cardiac muscle hypertrophy in response to stress | 3 | 109.0× | 5e-05 | MYH7, TCAP, MYH6 |
| regulation of muscle filament sliding | 2 | 581.1× | 5e-05 | MYLK2, MYBPC3 |
| striated muscle contraction | 3 | 87.2× | 9e-05 | MYLK2, MYH7, MYH6 |
| response to muscle stretch | 3 | 79.2× | 1e-04 | TCAP, ANKRD1, RAF1 |
| heart contraction | 3 | 79.2× | 1e-04 | SGCD, TNNI3, MYL2 |
| muscle contraction | 4 | 28.7× | 2e-04 | MYH7, MYH6, MYL3, OXTR |
| skeletal muscle contraction | 3 | 52.8× | 3e-04 | MYH7, TCAP, TNNI3 |
| regulation of heart rate | 3 | 48.4× | 4e-04 | MYH7, CAV3, MYH6 |
| T-tubule organization | 2 | 193.7× | 5e-04 | CAV3, CSRP3 |
| phospholipase C/protein kinase C signal transduction | 2 | 193.7× | 5e-04 | ANKRD1, CSRP3 |
| regulation of muscle contraction | 2 | 116.2× | 0.001 | TNNT2, TPM1 |
| negative regulation of ATP-dependent activity | 2 | 116.2× | 0.001 | TNNI3, TNNT2 |
| regulation of cardiac muscle contraction by calcium ion signaling | 2 | 89.4× | 0.002 | TNNI3, JPH2 |
| negative regulation of protein localization to cell surface | 2 | 89.4× | 0.002 | CAV3, ACTN2 |
| calcium ion transport into cytosol | 2 | 83.0× | 0.003 | CACNA1C, JPH2 |
| regulation of cardiac muscle cell contraction | 2 | 77.5× | 0.003 | MYH7B, MYBPC3 |
| dendrite self-avoidance | 2 | 72.6× | 0.003 | MYPN, NEXN |
Therapeutics
Drug target analysis
Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 7 · Undrugged: 23
Druggability breadth: 16 of 30 evidence-associated genes (53%) 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 |
|---|---|
| MYLK2 | FEDRATINIB |
| CACNA1C | REMIFENTANIL |
| GLA | CLOTRIMAZOLE |
| LMNA | BEPRIDIL |
| OXTR | DESMOPRESSIN |
| PRKAG2 | ADENOSINE PHOSPHATE |
| RAF1 | VEMURAFENIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| LMNA | 823 | 4 |
| CACNA1C | 85 | 4 |
| GLA | 62 | 4 |
| RAF1 | 31 | 4 |
| MYLK2 | 19 | 4 |
| PRKAG2 | 19 | 4 |
| OXTR | 15 | 4 |
| MYH7 | 0 | 0 |
| SGCD | 0 | 0 |
| TCAP | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| FEDRATINIB | 4 | MYLK2 |
| AXITINIB | 4 | MYLK2 |
| SORAFENIB | 4 | MYLK2, RAF1 |
| PAZOPANIB | 4 | MYLK2, RAF1 |
| NINTEDANIB | 4 | MYLK2 |
| SUNITINIB | 4 | CACNA1C, LMNA, MYLK2, PRKAG2 |
| DASATINIB | 4 | CACNA1C, MYLK2, RAF1 |
| ERLOTINIB | 4 | LMNA, MYLK2, RAF1 |
| GEFITINIB | 4 | MYLK2 |
| REMIFENTANIL | 4 | CACNA1C |
| BEPRIDIL | 4 | CACNA1C, LMNA |
| CLOTRIMAZOLE | 4 | CACNA1C, GLA, LMNA |
| PROPIVERINE | 4 | CACNA1C |
| DIBUCAINE | 4 | CACNA1C, LMNA |
| IMIPRAMINE | 4 | CACNA1C, LMNA |
| DULOXETINE | 4 | CACNA1C |
| QUINIDINE | 4 | CACNA1C |
| ESTRADIOL | 4 | CACNA1C, LMNA |
| TOLTERODINE | 4 | CACNA1C, LMNA |
| PIMOZIDE | 4 | CACNA1C, LMNA |
| NIMODIPINE | 4 | CACNA1C, LMNA |
| NICARDIPINE | 4 | CACNA1C, LMNA |
| AMLODIPINE | 4 | CACNA1C |
| VARDENAFIL | 4 | CACNA1C |
| CLEMASTINE | 4 | CACNA1C |
| ISRADIPINE | 4 | CACNA1C |
| TERFENADINE | 4 | CACNA1C, LMNA |
| NISOLDIPINE | 4 | CACNA1C, LMNA |
| SOLIFENACIN | 4 | CACNA1C |
| PINAVERIUM | 4 | CACNA1C |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| RAF1 | 839 | Binding:803, Functional:31, ADMET:5 |
| CACNA1C | 575 | Binding:319, Functional:211, Toxicity:26, ADMET:19 |
| PRKAG2 | 266 | Binding:265, Functional:1 |
| OXTR | 249 | Binding:149, Functional:99, Unclassified:1 |
| MYLK2 | 196 | Binding:196 |
| GLA | 114 | Binding:104, Functional:10 |
| LMNA | 12 | Binding:9, Functional:3 |
| TPM1 | 3 | Binding:3 |
| TNNI3 | 2 | Binding:2 |
| TNNT2 | 2 | Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| MYLK2 | 2.7.11.18 | myosin-light-chain kinase |
| GLA | 3.2.1.22 | alpha-galactosidase |
| RAF1 | 2.7.10.2 | non-specific protein-tyrosine kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| MYLK2 | 196 |
| CACNA1C | 575 |
| GLA | 114 |
| OXTR | 249 |
| PRKAG2 | 266 |
| RAF1 | 839 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 29; 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) |
|---|---|---|
| FEDRATINIB | 4 | MYLK2 |
| AXITINIB | 4 | MYLK2 |
| SORAFENIB | 4 | MYLK2, RAF1 |
| PAZOPANIB | 4 | MYLK2, RAF1 |
| NINTEDANIB | 4 | MYLK2 |
| SUNITINIB | 4 | CACNA1C, LMNA, MYLK2, PRKAG2 |
| DASATINIB | 4 | CACNA1C, MYLK2, RAF1 |
| ERLOTINIB | 4 | LMNA, MYLK2, RAF1 |
| GEFITINIB | 4 | MYLK2 |
| REMIFENTANIL | 4 | CACNA1C |
| BEPRIDIL | 4 | CACNA1C, LMNA |
| CLOTRIMAZOLE | 4 | CACNA1C, GLA, LMNA |
| PROPIVERINE | 4 | CACNA1C |
| DIBUCAINE | 4 | CACNA1C, LMNA |
| IMIPRAMINE | 4 | CACNA1C, LMNA |
| DULOXETINE | 4 | CACNA1C |
| QUINIDINE | 4 | CACNA1C |
| ESTRADIOL | 4 | CACNA1C, LMNA |
| TOLTERODINE | 4 | CACNA1C, LMNA |
| PIMOZIDE | 4 | CACNA1C, LMNA |
| NIMODIPINE | 4 | CACNA1C, LMNA |
| NICARDIPINE | 4 | CACNA1C, LMNA |
| AMLODIPINE | 4 | CACNA1C |
| VARDENAFIL | 4 | CACNA1C |
| CLEMASTINE | 4 | CACNA1C |
| ISRADIPINE | 4 | CACNA1C |
| TERFENADINE | 4 | CACNA1C, LMNA |
| NISOLDIPINE | 4 | CACNA1C, LMNA |
| SOLIFENACIN | 4 | CACNA1C |
| PINAVERIUM | 4 | CACNA1C |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 7 | MYLK2, CACNA1C, GLA, LMNA, OXTR, PRKAG2, RAF1 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 2 | OBSCN, MYBPC3 |
| D | Druggable family + AlphaFold only, no drug | 2 | MYPN, NEXN |
| E | Difficult family or no structure, no drug | 19 | MYH7, SGCD, TCAP, TNNI3, TNNT2, TPM1, JPH2, CAV3, LDB3, ANKRD1 (+9 more) |
Undrugged target profiles
23 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| MYH7 | 0 | — |
| SGCD | 0 | — |
| TCAP | 0 | — |
| TNNI3 | 2 | — |
| TNNT2 | 2 | — |
| TPM1 | 3 | — |
| JPH2 | 0 | — |
| CAV3 | 0 | — |
| LDB3 | 0 | — |
| OBSCN | 0 | — |
| ANKRD1 | 0 | — |
| MYH7B | 0 | — |
| ACTN2 | 0 | — |
| MYPN | 0 | — |
| CSRP3 | 0 | — |
| NEXN | 0 | — |
| MHRT | 0 | — |
| LAMA4 | 0 | — |
| LZTR1 | 0 | — |
| MYBPC3 | 0 | — |
| MYH6 | 0 | — |
| MYL2 | 0 | — |
| MYL3 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.