Left ventricular noncompaction
diseaseOn this page
Also known as left ventricular hypertrabeculationleft ventricular non-compaction cardiomyopathyleft ventricular non-compaction syndromeleft ventricular noncompaction (disease)Lv non-compaction syndromeLVNCspongy myocardium
Summary
Left ventricular noncompaction (MONDO:0018901) is a disease (an umbrella term covering 13 Mondo subtypes) with 29 cohort genes and 7 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (6 cohort genes).
At a glance
- Umbrella term: 13 Mondo subtypes
- Cohort genes: 29
- ClinVar variants: 53
- Clinical trials: 7
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | left ventricular noncompaction |
| Mondo ID | MONDO:0018901 |
| OMIM | 604169 |
| Orphanet | 54260 |
| DOID | DOID:0060480 |
| NCIT | C99544 |
| UMLS | C1960469 |
| MedGen | 450531 |
| GARD | 0010985 |
| Is cancer (heuristic) | no |
Also known as: left ventricular hypertrabeculation · left ventricular non-compaction cardiomyopathy · left ventricular non-compaction syndrome · left ventricular noncompaction (disease) · Lv non-compaction syndrome · LVNC · spongy myocardium
Data availability: 53 ClinVar variants · 9 GenCC gene-disease records · 37 cell lines.
Disease family
An umbrella term covering 13 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › left ventricular noncompaction
Related subtypes (5): myocarditis, dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy
Subtypes (13): dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, left ventricular noncompaction 1, left ventricular noncompaction 2, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, left ventricular noncompaction 7, left ventricular noncompaction 8, left ventricular noncompaction 10, left ventricular noncompaction 9, left ventricular noncompaction 4, left ventricular noncompaction 5
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
53 retrieved; paginated sample, class counts are floors:
22 uncertain significance, 17 conflicting classifications of pathogenicity, 5 pathogenic, 4 pathogenic/likely pathogenic, 2 likely pathogenic, 1 benign/likely benign, 1 likely benign, 1 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 4075274 | NM_001103.4(ACTN2):c.210dup (p.Lys71Ter) | ACTN2 | Pathogenic | criteria provided, single submitter |
| 36473 | NM_170707.4(LMNA):c.1003C>T (p.Arg335Trp) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 208631 | NM_005932.4(MIPEP):c.1804G>T (p.Glu602Ter) | MIPEP | Pathogenic | criteria provided, single submitter |
| 164021 | NC_000011.10:g.47332110del | MYBPC3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 177698 | NM_000256.3(MYBPC3):c.1038_1042dupCGGCA | MYBPC3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14127 | NM_000257.4(MYH7):c.732+1G>A | MYH7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 181327 | NM_000257.4(MYH7):c.842G>C (p.Arg281Thr) | MYH7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 454395 | NM_000257.4(MYH7):c.732+2T>G | MYH7 | Pathogenic | criteria provided, single submitter |
| 208634 | GRCh37/hg19 13q12.12(chr13:23519916-24941516)x1 | PCOTH | Pathogenic | criteria provided, single submitter |
| 164378 | NM_000257.4(MYH7):c.1157A>G (p.Tyr386Cys) | MYH7 | Likely pathogenic | reviewed by expert panel |
| 42822 | NM_000257.4(MYH7):c.1106G>A (p.Arg369Gln) | MYH7 | Likely pathogenic | reviewed by expert panel |
| 45190 | NM_005159.5(ACTC1):c.806T>C (p.Ile269Thr) | GJD2-DT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 468745 | NM_002230.4(JUP):c.1507G>A (p.Gly503Ser) | JUP | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3112773 | NM_012330.4(KAT6B):c.5293C>A (p.Gln1765Lys) | KAT6B | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1359014 | NM_003482.4(KMT2D):c.11671G>A (p.Ala3891Thr) | KMT2D | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 194753 | NM_006059.4(LAMC3):c.2891-8C>T | LAMC3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 194958 | NM_006059.4(LAMC3):c.3250G>C (p.Glu1084Gln) | LAMC3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 194959 | NM_006059.4(LAMC3):c.3379G>A (p.Glu1127Lys) | LAMC3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 208630 | NM_005932.4(MIPEP):c.916C>T (p.Leu306Phe) | MIPEP | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 208632 | NM_005932.4(MIPEP):c.1027A>G (p.Lys343Glu) | MIPEP | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 208633 | NM_005932.4(MIPEP):c.1534C>G (p.His512Asp) | MIPEP | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 407331 | NM_000256.3(MYBPC3):c.2217G>A (p.Glu739=) | MYBPC3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 164264 | NM_000257.4(MYH7):c.5690G>A (p.Arg1897His) | MYH7 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 164299 | NM_000257.4(MYH7):c.3748C>T (p.Arg1250Trp) | MYH7 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 179201 | NM_000257.4(MYH7):c.4156C>T (p.Leu1386Phe) | MYH7 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 403313 | NM_001005242.3(PKP2):c.2302G>A (p.Asp768Asn) | PKP2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 165128 | NM_001035.3(RYR2):c.13291G>A (p.Glu4431Lys) | RYR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 511503 | NM_001267550.2(TTN):c.92151T>C (p.Tyr30717=) | TTN-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 520516 | NM_014391.3(ANKRD1):c.806G>A (p.Arg269Gln) | ANKRD1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 642389 | NM_004415.4(DSP):c.2894T>C (p.Leu965Pro) | DSP | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 65 · Orphanet: 105 · 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 |
|---|---|---|---|---|
| PKP2 | Definitive | Autosomal dominant | arrhythmogenic right ventricular dysplasia 9 | 6 |
| MIB1 | Moderate | Autosomal dominant | left ventricular noncompaction 7 | 5 |
| PRDM16 | Moderate | Autosomal dominant | left ventricular noncompaction 8 | 6 |
| MYH7 | Supportive | Autosomal dominant | left ventricular noncompaction | 20 |
| MYH7B | Supportive | Autosomal dominant | left ventricular noncompaction | |
| TNNT2 | Supportive | Autosomal dominant | left ventricular noncompaction | 12 |
| TPM1 | Supportive | Autosomal dominant | left ventricular noncompaction | 6 |
| BMP10 | Limited | Autosomal dominant | left ventricular noncompaction | 4 |
| SYNE2 | Limited | Autosomal dominant | left ventricular noncompaction | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| 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 |
| MYH7B | Orphanet:54260 | Left ventricular noncompaction |
| 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 |
| PKP2 | Orphanet:130 | Brugada syndrome |
| PKP2 | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| PKP2 | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| PKP2 | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| PKP2 | Orphanet:54260 | Left ventricular noncompaction |
| PRDM16 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| PRDM16 | Orphanet:1606 | 1p36 deletion syndrome |
| PRDM16 | Orphanet:54260 | Left ventricular noncompaction |
| SYNE2 | Orphanet:98853 | Autosomal dominant Emery-Dreifuss muscular dystrophy |
| MIB1 | Orphanet:54260 | Left ventricular noncompaction |
| RYR2 | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| RYR2 | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| RYR2 | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| RYR2 | Orphanet:3286 | Catecholaminergic polymorphic ventricular tachycardia |
| TAFAZZIN | Orphanet:111 | Barth syndrome |
| TAFAZZIN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TBX20 | Orphanet:54260 | Left ventricular noncompaction |
| TBX20 | Orphanet:99103 | Atrial septal defect, ostium secundum type |
| TTN | Orphanet:140922 | Titin-related limb-girdle muscular dystrophy R10 |
| TTN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| TTN | Orphanet:169186 | Autosomal recessive centronuclear myopathy |
| TTN | Orphanet:178464 | Hereditary myopathy with early respiratory failure |
| TTN | Orphanet:289377 | Early-onset myopathy with fatal cardiomyopathy |
| TTN | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| TTN | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| TTN | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| TTN | Orphanet:324604 | Classic multiminicore myopathy |
| TTN | Orphanet:334 | Hereditary atrial fibrillation |
| TTN | Orphanet:466921 | Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome |
| TTN | Orphanet:609 | Tibial muscular dystrophy |
| TTN | Orphanet:707983 | Early-onset autosomal recessive TTN-related distal myopathy |
| ANKRD1 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| 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 |
| HCN4 | Orphanet:130 | Brugada syndrome |
| HCN4 | Orphanet:166282 | Hereditary sick sinus syndrome |
Cohort genes → proteins
29 cohort genes, 27 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 29 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TNNT2 | HGNC:11949 | ENSG00000118194 | P45379 | Troponin T, cardiac muscle | gencc,clinvar |
| TPM1 | HGNC:12010 | ENSG00000140416 | P09493 | Tropomyosin alpha-1 chain | gencc,clinvar |
| MYH7B | HGNC:15906 | ENSG00000078814 | A7E2Y1 | Myosin-7B | gencc,clinvar |
| MYH7 | HGNC:7577 | ENSG00000092054 | P12883 | Myosin-7 | gencc,clinvar |
| PKP2 | HGNC:9024 | ENSG00000057294 | Q99959 | Plakophilin-2 | gencc,clinvar |
| PRDM16 | HGNC:14000 | ENSG00000142611 | Q9HAZ2 | Histone-lysine N-methyltransferase PRDM16 | gencc |
| SYNE2 | HGNC:17084 | ENSG00000054654 | Q8WXH0 | Nesprin-2 | gencc |
| BMP10 | HGNC:20869 | ENSG00000163217 | O95393 | Bone morphogenetic protein 10 | gencc |
| MIB1 | HGNC:21086 | ENSG00000101752 | Q86YT6 | E3 ubiquitin-protein ligase MIB1 | gencc |
| RYR2 | HGNC:10484 | ENSG00000198626 | Q92736 | Ryanodine receptor 2 | clinvar |
| TAFAZZIN | HGNC:11577 | ENSG00000102125 | Q16635 | Tafazzin | clinvar |
| TBX20 | HGNC:11598 | ENSG00000164532 | Q9UMR3 | T-box transcription factor TBX20 | clinvar |
| TTN | HGNC:12403 | ENSG00000155657 | Q8WZ42 | Titin | clinvar |
| ANKRD1 | HGNC:15819 | ENSG00000148677 | Q15327 | Ankyrin repeat domain-containing protein 1 | clinvar |
| ACTN2 | HGNC:164 | ENSG00000077522 | P35609 | Alpha-actinin-2 | clinvar |
| HCN4 | HGNC:16882 | ENSG00000138622 | Q9Y3Q4 | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | clinvar |
| KAT6B | HGNC:17582 | ENSG00000156650 | Q8WYB5 | Histone acetyltransferase KAT6B | clinvar |
| DSP | HGNC:3052 | ENSG00000096696 | P15924 | Desmoplakin | clinvar |
| PCOTH | HGNC:39839 | ENSG00000205861 | Q58A44 | Prostate collagen triple helix protein | clinvar |
| TTN-AS1 | HGNC:44124 | ENSG00000237298 | TTN antisense RNA 1 | clinvar | |
| GJD2-DT | HGNC:55560 | ENSG00000250007 | GJD2 divergent transcript | clinvar | |
| JUP | HGNC:6207 | ENSG00000173801 | P14923 | Junction plakoglobin | clinvar |
| LAMC3 | HGNC:6494 | ENSG00000050555 | Q9Y6N6 | Laminin subunit gamma-3 | clinvar |
| LMNA | HGNC:6636 | ENSG00000160789 | P02545 | Prelamin-A/C | clinvar |
| MIPEP | HGNC:7104 | ENSG00000027001 | Q99797 | Mitochondrial intermediate peptidase | clinvar |
| KMT2D | HGNC:7133 | ENSG00000167548 | O14686 | Histone-lysine N-methyltransferase 2D | clinvar |
| MYBPC3 | HGNC:7551 | ENSG00000134571 | Q14896 | Myosin-binding protein C, cardiac-type | clinvar |
| MYH6 | HGNC:7576 | ENSG00000197616 | P13533 | Myosin-6 | clinvar |
| PDGFRB | HGNC:8804 | ENSG00000113721 | P09619 | Platelet-derived growth factor receptor beta | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| 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. |
| MYH7B | Myosin-7B | Involved in muscle contraction. |
| MYH7 | Myosin-7 | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. |
| PKP2 | Plakophilin-2 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
| PRDM16 | Histone-lysine N-methyltransferase PRDM16 | Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context. |
| SYNE2 | Nesprin-2 | Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. |
| BMP10 | Bone morphogenetic protein 10 | Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors suc… |
| MIB1 | E3 ubiquitin-protein ligase MIB1 | E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. |
| RYR2 | Ryanodine receptor 2 | Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. |
| TAFAZZIN | Tafazzin | Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1’,3’-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary fo… |
| TBX20 | T-box transcription factor TBX20 | Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart. |
| TTN | Titin | Key component in the assembly and functioning of vertebrate striated muscles. |
| ANKRD1 | Ankyrin repeat domain-containing protein 1 | May play an important role in endothelial cell activation. |
| ACTN2 | Alpha-actinin-2 | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. |
| HCN4 | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | Hyperpolarization-activated ion channel that are permeable to Na(+) and K(+) ions with very slow activation and inactivation. |
| KAT6B | Histone acetyltransferase KAT6B | Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. |
| DSP | Desmoplakin | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
| PCOTH | Prostate collagen triple helix protein | May be involved in growth and survival of prostate cancer cells through the TAF-Ibeta pathway. |
| JUP | Junction plakoglobin | Common junctional plaque protein. |
| LAMC3 | Laminin subunit gamma-3 | 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. |
| MIPEP | Mitochondrial intermediate peptidase | Cleaves proteins, imported into the mitochondrion, to their mature size. |
| KMT2D | Histone-lysine N-methyltransferase 2D | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4). |
| 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. |
| PDGFRB | Platelet-derived growth factor receptor beta | Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, surviv… |
Protein-family classification
Druggable: 5 · Difficult: 10 · Unknown: 14 · Druggable fraction: 0.17
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 | 2 | 7.7× | 0.083 |
| Scaffold/PPI | 5 | 3.0× | 0.083 |
| Kinase | 2 | 1.9× | 0.422 |
| Transcription factor | 5 | 1.4× | 0.422 |
| Antibody/Immunoglobulin | 1 | 1.0× | 0.764 |
| Other/Unknown | 14 | 0.9× | 0.843 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TNNT2 | Other/Unknown | no | Troponin, TNNT, Troponin_sf | |
| TPM1 | Other/Unknown | no | Tropomyosin | |
| MYH7B | Scaffold/PPI | no | Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin | |
| MYH7 | Scaffold/PPI | no | IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail | |
| PKP2 | Other/Unknown | no | Armadillo, ARM-like, ARM-type_fold | |
| PRDM16 | Transcription factor | no | 2.1.1.367 | SET_dom, Znf_C2H2_type, Znf_C2H2_sf |
| SYNE2 | Other/Unknown | no | Actinin_actin-bd_CS, CH_dom, Spectrin_repeat | |
| BMP10 | Other/Unknown | no | TGF-b_propeptide, TGF-b_C, TGF-beta-like | |
| MIB1 | Transcription factor | no | Znf_ZZ, Znf_RING, Ankyrin_rpt | |
| RYR2 | Ion channel | yes | RIH_dom, B30.2/SPRY, EF_hand_dom | |
| TAFAZZIN | Other/Unknown | no | Tafazzin, Plipid/glycerol_acylTrfase | |
| TBX20 | Transcription factor | no | TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS | |
| TTN | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ig_sub2, Ig_sub |
| ANKRD1 | Scaffold/PPI | no | Ankyrin_rpt, Ankyrin_rpt-contain_sf | |
| ACTN2 | Other/Unknown | no | Actinin_actin-bd_CS, CH_dom, Spectrin_repeat | |
| HCN4 | Ion channel | yes | cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom | |
| KAT6B | Transcription factor | no | 2.3.1.48 | Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15 |
| DSP | Scaffold/PPI | no | Plectin_repeat, SH3_domain, Spectrin/alpha-actinin | |
| PCOTH | Other/Unknown | no | ||
| TTN-AS1 | Other/Unknown | no | ||
| GJD2-DT | Other/Unknown | no | ||
| JUP | Other/Unknown | no | Armadillo, ARM-like, Beta-catenin | |
| LAMC3 | Other/Unknown | no | Laminin_IV, EGF, LE_dom | |
| LMNA | Other/Unknown | no | Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf | |
| MIPEP | Other/Unknown | no | Pept_M3A_M3B_dom, Neurolysin/TOP_dom2, MetalloPept_cat_dom_sf | |
| KMT2D | Transcription factor | no | SET_dom, Znf_RING, Znf_PHD | |
| MYBPC3 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| MYH6 | Scaffold/PPI | no | Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin | |
| PDGFRB | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS |
Expression context
Cohort genes with no expression data: 0.
24 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 | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| apex of heart | 9 |
| right atrium auricular region | 9 |
| cardiac atrium | 8 |
| hindlimb stylopod muscle | 4 |
| skeletal muscle tissue of biceps brachii | 4 |
| heart right ventricle | 3 |
| left ventricle myocardium | 3 |
| sural nerve | 3 |
| myocardium | 2 |
| heart left ventricle | 2 |
| ventricular zone | 2 |
| cardiac muscle of right atrium | 2 |
| lower esophagus mucosa | 2 |
| skin of abdomen | 2 |
| endocervix | 2 |
| ascending aorta | 1 |
| pigmented layer of retina | 1 |
| ganglionic eminence | 1 |
| corpus epididymis | 1 |
| kidney epithelium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TNNT2 | 154 | broad | marker | apex of heart, right atrium auricular region, cardiac atrium |
| TPM1 | 305 | ubiquitous | marker | left ventricle myocardium, heart right ventricle, myocardium |
| MYH7B | 195 | broad | yes | apex of heart, hindlimb stylopod muscle, heart left ventricle |
| MYH7 | 167 | tissue_specific | marker | apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of biceps brachii |
| PKP2 | 237 | ubiquitous | marker | heart right ventricle, apex of heart, left ventricle myocardium |
| PRDM16 | 202 | broad | marker | sural nerve, pigmented layer of retina, ascending aorta |
| SYNE2 | 284 | ubiquitous | marker | ventricular zone, skeletal muscle tissue of biceps brachii, ganglionic eminence |
| BMP10 | 90 | tissue_specific | marker | cardiac muscle of right atrium, right atrium auricular region, cardiac atrium |
| MIB1 | 262 | ubiquitous | marker | corpus epididymis, kidney epithelium, tibia |
| RYR2 | 210 | broad | marker | heart right ventricle, left ventricle myocardium, myocardium |
| TAFAZZIN | 238 | ubiquitous | marker | apex of heart, granulocyte, lower esophagus mucosa |
| TBX20 | 52 | broad | marker | right atrium auricular region, cardiac atrium, heart |
| TTN | 223 | broad | marker | biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii |
| ANKRD1 | 155 | ubiquitous | marker | apex of heart, right atrium auricular region, cardiac atrium |
| ACTN2 | 226 | broad | marker | skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle |
| HCN4 | 86 | tissue_specific | yes | tibialis anterior, right atrium auricular region, cardiac atrium |
| KAT6B | 140 | ubiquitous | yes | cortical plate, ventricular zone, sural nerve |
| DSP | 253 | ubiquitous | marker | skin of hip, upper leg skin, hair follicle |
| PCOTH | 170 | broad | marker | right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis |
| TTN-AS1 | 174 | ubiquitous | marker | hindlimb stylopod muscle, gastrocnemius, right atrium auricular region |
| GJD2-DT | 114 | yes | right atrium auricular region, apex of heart, heart left ventricle | |
| JUP | 287 | ubiquitous | marker | lower esophagus mucosa, skin of leg, skin of abdomen |
| LAMC3 | 184 | broad | marker | endocervix, metanephros cortex, right lung |
| LMNA | 295 | ubiquitous | marker | nipple, mucosa of stomach, skin of abdomen |
| MIPEP | 248 | ubiquitous | marker | right atrium auricular region, apex of heart, cardiac atrium |
| KMT2D | 272 | ubiquitous | marker | buccal mucosa cell, medial globus pallidus, sural nerve |
| 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 |
| PDGFRB | 270 | ubiquitous | marker | stromal cell of endometrium, right coronary artery, endocervix |
Protein interactions among cohort
Intra-cohort edges: 32.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LMNA | 7,173 |
| PDGFRB | 5,111 |
| JUP | 4,618 |
| TTN | 4,237 |
| TPM1 | 3,514 |
| KMT2D | 3,223 |
| MYH6 | 3,119 |
| DSP | 2,897 |
| ACTN2 | 2,781 |
| MYH7 | 2,744 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ACTN2 | MYH6 | biogrid_interaction, string_interaction |
| ACTN2 | MYH7 | biogrid_interaction, string_interaction |
| ACTN2 | TNNT2 | string_interaction |
| ACTN2 | TPM1 | biogrid_interaction, string_interaction |
| ACTN2 | TTN | string_interaction |
| ANKRD1 | TTN | biogrid_interaction, string_interaction |
| BMP10 | MYH6 | string_interaction |
| BMP10 | MYH7 | string_interaction |
| DSP | JUP | intact, string_interaction |
| DSP | PKP2 | string_interaction |
| JUP | LMNA | string_interaction |
| JUP | PKP2 | string_interaction |
| JUP | RYR2 | string_interaction |
| LMNA | PKP2 | string_interaction |
| LMNA | SYNE2 | string_interaction |
| MYBPC3 | MYH6 | string_interaction |
| MYBPC3 | MYH7 | intact, string_interaction |
| MYBPC3 | TNNT2 | string_interaction |
| MYBPC3 | TPM1 | string_interaction |
| MYBPC3 | TTN | string_interaction |
| MYH6 | TBX20 | string_interaction |
| MYH6 | TNNT2 | string_interaction |
| MYH6 | TTN | string_interaction |
| MYH7 | TNNT2 | string_interaction |
| MYH7 | TPM1 | string_interaction |
| MYH7 | TTN | string_interaction |
| MYH7B | TPM1 | biogrid_interaction |
| PKP2 | RYR2 | string_interaction |
| TAFAZZIN | TNNT2 | string_interaction |
| TBX20 | TNNT2 | string_interaction |
| TNNT2 | TPM1 | string_interaction |
| TPM1 | TTN | string_interaction |
Structural data
PDB: 19 · AlphaFold-only: 8 · No structure: 2
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TTN | Q8WZ42 | 64 |
| MYH7 | P12883 | 43 |
| LMNA | P02545 | 28 |
| RYR2 | Q92736 | 26 |
| TNNT2 | P45379 | 25 |
| MYBPC3 | Q14896 | 17 |
| ACTN2 | P35609 | 16 |
| TPM1 | P09493 | 14 |
| KMT2D | O14686 | 11 |
| BMP10 | O95393 | 8 |
| HCN4 | Q9Y3Q4 | 8 |
| PDGFRB | P09619 | 8 |
| MIB1 | Q86YT6 | 6 |
| DSP | P15924 | 4 |
| SYNE2 | Q8WXH0 | 3 |
| KAT6B | Q8WYB5 | 3 |
| PRDM16 | Q9HAZ2 | 2 |
| PKP2 | Q99959 | 1 |
| JUP | P14923 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| TAFAZZIN | Q16635 | 94.87 |
| MIPEP | Q99797 | 90.33 |
| ANKRD1 | Q15327 | 82.64 |
| PCOTH | Q58A44 | 78.90 |
| LAMC3 | Q9Y6N6 | 75.23 |
| MYH6 | P13533 | 74.91 |
| MYH7B | A7E2Y1 | 73.79 |
| TBX20 | Q9UMR3 | 67.87 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 138. Enrichment computed across 29 evidence-associated genes (23 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 23 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 | 6 | 80.5× | 1e-08 | TNNT2, TPM1, TTN, ACTN2, MYBPC3, MYH6 |
| Muscle contraction | 4 | 13.4× | 0.014 | RYR2, ACTN2, MYBPC3, MYH6 |
| Formation of the cornified envelope | 3 | 11.5× | 0.099 | PKP2, DSP, JUP |
| Breakdown of the nuclear lamina | 1 | 165.5× | 0.157 | LMNA |
| HCN channels | 1 | 124.1× | 0.157 | HCN4 |
| Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome | 1 | 99.3× | 0.157 | KMT2D |
| Acyl chain remodeling of CL | 1 | 82.8× | 0.157 | TAFAZZIN |
| CDH11 homotypic and heterotypic interactions | 1 | 70.9× | 0.157 | JUP |
| Regulation of CDH19 Expression and Function | 1 | 62.1× | 0.157 | JUP |
| Signaling by NOTCH1 HD Domain Mutants in Cancer | 1 | 55.2× | 0.157 | MIB1 |
| Apoptotic cleavage of cell adhesion proteins | 1 | 45.1× | 0.157 | DSP |
| Regulation of CDH11 function | 1 | 45.1× | 0.157 | JUP |
| Regulation of CDH1 Function | 1 | 41.4× | 0.157 | JUP |
| CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 1 | 38.2× | 0.157 | ACTN2 |
| Constitutive Signaling by NOTCH1 HD Domain Mutants | 1 | 33.1× | 0.157 | MIB1 |
| Depolymerization of the Nuclear Lamina | 1 | 33.1× | 0.157 | LMNA |
| Signaling by NOTCH2 | 1 | 31.0× | 0.157 | MIB1 |
| Initiation of Nuclear Envelope (NE) Reformation | 1 | 26.1× | 0.157 | LMNA |
| MET promotes cell motility | 1 | 26.1× | 0.157 | LAMC3 |
| Ras activation upon Ca2+ influx through NMDA receptor | 1 | 24.8× | 0.157 | ACTN2 |
| Unblocking of NMDA receptors, glutamate binding and activation | 1 | 23.6× | 0.157 | ACTN2 |
| Negative regulation of NMDA receptor-mediated neuronal transmission | 1 | 23.6× | 0.157 | ACTN2 |
| IRE1alpha activates chaperones | 1 | 22.6× | 0.157 | LMNA |
| Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models | 1 | 22.6× | 0.157 | LMNA |
| Signaling by NOTCH3 | 1 | 22.6× | 0.157 | MIB1 |
| Attachment of bacteria to epithelial cells | 1 | 21.6× | 0.157 | LAMC3 |
| SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST) | 1 | 21.6× | 0.157 | JUP |
| Nephrin family interactions | 1 | 20.7× | 0.157 | ACTN2 |
| NOTCH3 Activation and Transmission of Signal to the Nucleus | 1 | 20.7× | 0.157 | MIB1 |
| Long-term potentiation | 1 | 20.7× | 0.157 | 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 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| ventricular cardiac muscle tissue morphogenesis | 7 | 189.0× | 5e-13 | TNNT2, TPM1, MYH7, PKP2, BMP10, MYBPC3, MYH6 |
| sarcomere organization | 8 | 117.8× | 5e-13 | TNNT2, TPM1, TTN, ANKRD1, ACTN2, BMP10, MYBPC3, MYH6 |
| cardiac muscle contraction | 7 | 108.0× | 2e-11 | TNNT2, TPM1, MYH7, RYR2, TTN, MYBPC3, MYH6 |
| muscle filament sliding | 5 | 202.6× | 2e-09 | TNNT2, TPM1, MYH7, TTN, MYH6 |
| regulation of ventricular cardiac muscle cell action potential | 4 | 216.1× | 1e-07 | PKP2, RYR2, DSP, JUP |
| striated muscle contraction | 4 | 129.6× | 1e-06 | MYH7, RYR2, TTN, MYH6 |
| bundle of His cell-Purkinje myocyte adhesion involved in cell communication | 3 | 277.8× | 5e-06 | PKP2, DSP, JUP |
| muscle contraction | 5 | 40.0× | 6e-06 | MYH7, TBX20, TTN, HCN4, MYH6 |
| regulation of heart rate | 4 | 72.0× | 9e-06 | MYH7, RYR2, HCN4, MYH6 |
| regulation of heart rate by cardiac conduction | 4 | 57.6× | 2e-05 | PKP2, HCN4, DSP, JUP |
| cardiac muscle tissue morphogenesis | 3 | 162.0× | 2e-05 | TBX20, TTN, ANKRD1 |
| adult heart development | 3 | 138.9× | 3e-05 | MYH7, BMP10, MYH6 |
| regulation of cardiac muscle contraction | 3 | 102.3× | 8e-05 | RYR2, HCN4, BMP10 |
| cardiac muscle cell development | 3 | 72.0× | 2e-04 | TTN, ACTN2, MYH6 |
| regulation of heart contraction | 3 | 57.2× | 4e-04 | TNNT2, TPM1, MYH6 |
| regulation of SA node cell action potential | 2 | 216.1× | 7e-04 | RYR2, HCN4 |
| desmosome assembly | 2 | 185.2× | 9e-04 | PKP2, JUP |
| atrial cardiac muscle tissue morphogenesis | 2 | 185.2× | 9e-04 | BMP10, MYH6 |
| desmosome organization | 2 | 162.0× | 0.001 | PKP2, DSP |
| embryonic heart tube morphogenesis | 2 | 144.0× | 0.001 | RYR2, TBX20 |
| cardiac muscle hypertrophy | 2 | 129.6× | 0.001 | RYR2, TTN |
| regulation of muscle contraction | 2 | 129.6× | 0.001 | TNNT2, TPM1 |
| ventricular cardiac muscle cell development | 2 | 117.8× | 0.002 | BMP10, LMNA |
| cell communication by electrical coupling involved in cardiac conduction | 2 | 108.0× | 0.002 | PKP2, RYR2 |
| cardiac myofibril assembly | 2 | 99.7× | 0.002 | TTN, PDGFRB |
| regulation of cardiac muscle cell contraction | 2 | 86.4× | 0.003 | MYH7B, MYBPC3 |
| cardiac muscle hypertrophy in response to stress | 2 | 81.0× | 0.003 | MYH7, MYH6 |
| regulation of the force of heart contraction | 2 | 76.2× | 0.003 | MYH7, MYH6 |
| ventricular cardiac muscle cell action potential | 2 | 76.2× | 0.003 | PKP2, RYR2 |
| response to muscle stretch | 2 | 58.9× | 0.006 | RYR2, ANKRD1 |
Therapeutics
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 4 · Undrugged: 25
Druggability breadth: 18 of 29 evidence-associated genes (62%) 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 |
|---|---|
| HCN4 | IVABRADINE |
| LMNA | BEPRIDIL |
| PDGFRB | PONATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| LMNA | 823 | 4 |
| PDGFRB | 102 | 4 |
| HCN4 | 2 | 4 |
| RYR2 | 1 | 2 |
| TNNT2 | 0 | 0 |
| TPM1 | 0 | 0 |
| MYH7B | 0 | 0 |
| MYH7 | 0 | 0 |
| PKP2 | 0 | 0 |
| PRDM16 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| IVABRADINE | 4 | HCN4 |
| BEPRIDIL | 4 | LMNA |
| PHENYLBUTAZONE | 4 | LMNA |
| CEFOTAXIME SODIUM | 4 | LMNA |
| DIENESTROL | 4 | LMNA |
| IFOSFAMIDE | 4 | LMNA |
| PROGESTERONE | 4 | LMNA |
| CLOTRIMAZOLE | 4 | LMNA |
| DAPSONE | 4 | LMNA |
| AMINOCAPROIC ACID | 4 | LMNA |
| FLUCONAZOLE | 4 | LMNA |
| COLCHICINE | 4 | LMNA |
| NABUMETONE | 4 | LMNA |
| OXAPROZIN | 4 | LMNA |
| BUMETANIDE | 4 | LMNA |
| GLIPIZIDE | 4 | LMNA |
| BROMFENAC | 4 | LMNA |
| ROPIVACAINE | 4 | LMNA |
| TIZANIDINE | 4 | LMNA |
| METAXALONE | 4 | LMNA |
| CARBAMAZEPINE | 4 | LMNA |
| SALMETEROL XINAFOATE | 4 | LMNA |
| AMIODARONE HYDROCHLORIDE | 4 | LMNA |
| METHYL SALICYLATE | 4 | LMNA |
| DIBUCAINE | 4 | LMNA |
| PHENELZINE | 4 | LMNA |
| HYDROCORTISONE ACETATE | 4 | LMNA |
| BRETYLIUM TOSYLATE | 4 | LMNA |
| IMIPRAMINE | 4 | LMNA |
| FURAZOLIDONE | 4 | LMNA |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 4.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PDGFRB | 1,237 | Binding:1213, Functional:16, ADMET:8 |
| HCN4 | 30 | Binding:20, ADMET:5, Functional:4, Toxicity:1 |
| KAT6B | 22 | Binding:20, Functional:2 |
| RYR2 | 15 | Binding:15 |
| LMNA | 12 | Binding:9, Functional:3 |
| KMT2D | 11 | Binding:11 |
| TPM1 | 3 | Binding:3 |
| TNNT2 | 2 | Binding:2 |
| PRDM16 | 2 | Binding:2 |
| DSP | 2 | Binding:2 |
| TAFAZZIN | 1 | Binding:1 |
| TTN | 1 | Binding:1 |
| JUP | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PRDM16 | 2.1.1.367, 2.1.1.370 | [histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine4 N-dimethyltransferase |
| TTN | 2.7.11.1 | non-specific serine/threonine protein kinase |
| KAT6B | 2.3.1.48 | histone acetyltransferase |
| PDGFRB | 2.7.10.1 | receptor 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 |
|---|---|
| PDGFRB | 1,237 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 26; 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) |
|---|---|---|
| IVABRADINE | 4 | HCN4 |
| BEPRIDIL | 4 | LMNA |
| PHENYLBUTAZONE | 4 | LMNA |
| CEFOTAXIME SODIUM | 4 | LMNA |
| DIENESTROL | 4 | LMNA |
| IFOSFAMIDE | 4 | LMNA |
| PROGESTERONE | 4 | LMNA |
| CLOTRIMAZOLE | 4 | LMNA |
| DAPSONE | 4 | LMNA |
| AMINOCAPROIC ACID | 4 | LMNA |
| FLUCONAZOLE | 4 | LMNA |
| COLCHICINE | 4 | LMNA |
| NABUMETONE | 4 | LMNA |
| OXAPROZIN | 4 | LMNA |
| BUMETANIDE | 4 | LMNA |
| GLIPIZIDE | 4 | LMNA |
| BROMFENAC | 4 | LMNA |
| ROPIVACAINE | 4 | LMNA |
| TIZANIDINE | 4 | LMNA |
| METAXALONE | 4 | LMNA |
| CARBAMAZEPINE | 4 | LMNA |
| SALMETEROL XINAFOATE | 4 | LMNA |
| AMIODARONE HYDROCHLORIDE | 4 | LMNA |
| METHYL SALICYLATE | 4 | LMNA |
| DIBUCAINE | 4 | LMNA |
| PHENELZINE | 4 | LMNA |
| HYDROCORTISONE ACETATE | 4 | LMNA |
| BRETYLIUM TOSYLATE | 4 | LMNA |
| IMIPRAMINE | 4 | LMNA |
| FURAZOLIDONE | 4 | LMNA |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | HCN4, LMNA, PDGFRB |
| B | Phased (≥1) drug, not yet approved | 1 | RYR2 |
| C | Druggable family + PDB, no drug | 2 | TTN, MYBPC3 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 23 | TNNT2, TPM1, MYH7B, MYH7, PKP2, PRDM16, SYNE2, BMP10, MIB1, TAFAZZIN (+13 more) |
Undrugged target profiles
25 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| SYNE2 | 0 | LMNA |
| TNNT2 | 2 | — |
| TPM1 | 3 | — |
| MYH7B | 0 | — |
| MYH7 | 0 | — |
| PKP2 | 0 | — |
| PRDM16 | 2 | — |
| BMP10 | 0 | — |
| MIB1 | 0 | — |
| TAFAZZIN | 1 | — |
| TBX20 | 0 | — |
| TTN | 1 | — |
| ANKRD1 | 0 | — |
| ACTN2 | 0 | — |
| KAT6B | 22 | — |
| DSP | 2 | — |
| PCOTH | 0 | — |
| TTN-AS1 | 0 | — |
| GJD2-DT | 0 | — |
| JUP | 1 | — |
| LAMC3 | 0 | — |
| MIPEP | 0 | — |
| KMT2D | 11 | — |
| MYBPC3 | 0 | — |
| MYH6 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 7.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 7 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02432092 | Not specified | RECRUITING | Pediatric Cardiomyopathy Mutation Analysis |
| NCT06024759 | Not specified | RECRUITING | Predictors of Risk in Left Ventricular Non-Compaction |
| NCT06607471 | Not specified | RECRUITING | Multimodal and Multidisciplinary Approach to Optimize Diagnostic, Prognostic, and Therapeutic Management of Patients with Non-ischemic Cardiomyopathies and Arrhythmogenic-inflammatory Phenotypes: a Multicenter, Observational, Retrospective and Prospective Registry Study. |
| NCT01470014 | Not specified | COMPLETED | Cardiac Computed Tomography: Characteristics of Isolated Left Ventricular Non-compaction |
| NCT01481298 | Not specified | COMPLETED | Value of Cardiac Magnetic Resonance (CMR) Derived Parameters for Diagnosing Left Ventricular Non-compaction Cardiomyopathy |
| NCT02568072 | Not specified | COMPLETED | Training-induced Increased Left Ventricular Trabeculation |
| NCT03572569 | Not specified | UNKNOWN | Risk Stratification in Children and Adolescents With Primary Cardiomyopathy |