Left ventricular noncompaction 1
diseaseOn this page
Also known as DTNA left ventricular noncompactionleft ventricular noncompaction 1, with or without congenital heart defectsleft ventricular noncompaction caused by mutation in DTNAleft ventricular noncompaction type 1LVNC1
Summary
Left ventricular noncompaction 1 (MONDO:0011403) is a disease with 14 cohort genes. The dominant Reactome pathway is Striated Muscle Contraction (4 cohort genes).
At a glance
- Cohort genes: 14
- ClinVar variants: 576
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | left ventricular noncompaction 1 |
| Mondo ID | MONDO:0011403 |
| OMIM | 604169 |
| UMLS | C1858725 |
| MedGen | 349005 |
| GARD | 0024797 |
| Is cancer (heuristic) | no |
Also known as: DTNA left ventricular noncompaction · left ventricular noncompaction 1 · left ventricular noncompaction 1, with or without congenital heart defects · left ventricular noncompaction caused by mutation in DTNA · left ventricular noncompaction type 1 · LVNC1
Data availability: 576 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 › left ventricular noncompaction › left ventricular noncompaction 1
Related subtypes (12): dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, 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
576 retrieved; paginated sample, class counts are floors:
305 uncertain significance, 207 likely benign, 29 conflicting classifications of pathogenicity, 17 benign/likely benign, 16 benign, 2 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 42650 | NM_000256.3(MYBPC3):c.2670G>A (p.Trp890Ter) | MYBPC3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 8603 | NM_000256.3(MYBPC3):c.3742_3759dup (p.Gly1248_Cys1253dup) | MYBPC3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 532043 | NM_001103.4(ACTN2):c.1625T>C (p.Met542Thr) | ACTN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 298956 | NM_004281.4(BAG3):c.415C>T (p.Arg139Trp) | BAG3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 140609 | NM_001386795.1(DTNA):c.2224G>T (p.Val742Phe) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1586700 | NM_001386795.1(DTNA):c.1002-2320T>A | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 179015 | NM_001386795.1(DTNA):c.1766G>A (p.Arg589His) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 180346 | NM_001386795.1(DTNA):c.1330C>T (p.Arg444Trp) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 191651 | NM_001386795.1(DTNA):c.955A>G (p.Met319Val) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 191653 | NM_001386795.1(DTNA):c.1695C>T (p.Ser565=) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 191654 | NM_001386795.1(DTNA):c.1838C>T (p.Pro613Leu) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 191656 | NM_001386795.1(DTNA):c.2039G>A (p.Arg680Gln) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201762 | NM_001386795.1(DTNA):c.1454G>C (p.Ser485Thr) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 201763 | NM_001386795.1(DTNA):c.*2600C>T | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2505326 | NM_001386795.1(DTNA):c.1265del (p.Ser422fs) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2506266 | NM_001386795.1(DTNA):c.148+8T>C | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2982772 | NM_001386795.1(DTNA):c.2140A>G (p.Thr714Ala) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 326663 | NM_001386795.1(DTNA):c.476G>A (p.Ser159Asn) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 374197 | NM_001386795.1(DTNA):c.177A>G (p.Ile59Met) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 389076 | NM_001386795.1(DTNA):c.423A>G (p.Gly141=) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 445896 | NM_001386795.1(DTNA):c.229A>G (p.Asn77Asp) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 46410 | NM_001386795.1(DTNA):c.1000G>A (p.Val334Met) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 46412 | NM_001386795.1(DTNA):c.1480G>A (p.Asp494Asn) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 46422 | NM_001386795.1(DTNA):c.2108G>A (p.Arg703Gln) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 46431 | NM_001386795.1(DTNA):c.1297C>T (p.His433Tyr) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 523441 | NM_001386795.1(DTNA):c.68-7G>A | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 704504 | NM_001386795.1(DTNA):c.1562G>A (p.Arg521Gln) | DTNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 450709 | NM_000256.3(MYBPC3):c.362C>T (p.Pro121Leu) | MYBPC3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 264214 | NM_002471.4(MYH6):c.5519A>G (p.Lys1840Arg) | MYH6 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 14114 | NM_000257.4(MYH7):c.5533C>T (p.Arg1845Trp) | MYH7 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 49 · 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 |
|---|---|---|---|---|
| DTNA | Limited | Autosomal dominant | left ventricular noncompaction 1 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| DTNA | Orphanet:54260 | Left ventricular noncompaction |
| SCN5A | Orphanet:101016 | Romano-Ward syndrome |
| SCN5A | Orphanet:130 | Brugada syndrome |
| SCN5A | Orphanet:1344 | Isolated atrial standstill |
| SCN5A | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| SCN5A | Orphanet:166282 | Hereditary sick sinus syndrome |
| SCN5A | Orphanet:228140 | Idiopathic ventricular fibrillation |
| SCN5A | Orphanet:334 | Hereditary atrial fibrillation |
| SCN5A | Orphanet:871 | Hereditary progressive cardiac conduction defect |
| ACTC1 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| ACTC1 | Orphanet:54260 | Left ventricular noncompaction |
| ACTC1 | Orphanet:99103 | Atrial septal defect, ostium secundum type |
| 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 |
| 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 |
| JUP | Orphanet:158687 | Lethal acantholytic erosive disorder |
| JUP | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| JUP | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| JUP | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| JUP | Orphanet:34217 | Naxos disease |
| MYBPC3 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| MYBPC3 | Orphanet:54260 | Left ventricular noncompaction |
| MYH6 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| MYH6 | Orphanet:166282 | Hereditary sick sinus syndrome |
| MYH6 | Orphanet:99103 | Atrial septal defect, ostium secundum type |
| 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 |
| BAG3 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| BAG3 | Orphanet:199340 | BAG3-related myofibrillar myopathy |
Cohort genes → proteins
14 cohort genes, 12 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 14 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| DTNA | HGNC:3057 | ENSG00000134769 | Q9Y4J8 | Dystrobrevin alpha | gencc,clinvar |
| SCN5A | HGNC:10593 | ENSG00000183873 | Q14524 | Sodium channel protein type 5 subunit alpha | clinvar |
| ACTC1 | HGNC:143 | ENSG00000159251 | P68032 | Actin, alpha cardiac muscle 1 | clinvar |
| LDB3 | HGNC:15710 | ENSG00000122367 | O75112 | LIM domain-binding protein 3 | clinvar |
| ACTN2 | HGNC:164 | ENSG00000077522 | P35609 | Alpha-actinin-2 | clinvar |
| MYPN | HGNC:23246 | ENSG00000138347 | Q86TC9 | Myopalladin | clinvar |
| GJD2-DT | HGNC:55560 | ENSG00000250007 | GJD2 divergent transcript | clinvar | |
| DTNA-AS1 | HGNC:58208 | ENSG00000268873 | DTNA antisense RNA 1 | clinvar | |
| JUP | HGNC:6207 | ENSG00000173801 | P14923 | Junction plakoglobin | clinvar |
| MYBPC3 | HGNC:7551 | ENSG00000134571 | Q14896 | Myosin-binding protein C, cardiac-type | clinvar |
| MYH6 | HGNC:7576 | ENSG00000197616 | P13533 | Myosin-6 | clinvar |
| MYH7 | HGNC:7577 | ENSG00000092054 | P12883 | Myosin-7 | clinvar |
| PKP2 | HGNC:9024 | ENSG00000057294 | Q99959 | Plakophilin-2 | clinvar |
| BAG3 | HGNC:939 | ENSG00000151929 | O95817 | BAG family molecular chaperone regulator 3 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| DTNA | Dystrobrevin alpha | May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors. |
| SCN5A | Sodium channel protein type 5 subunit alpha | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. |
| ACTC1 | Actin, alpha cardiac muscle 1 | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| 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. |
| 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. |
| JUP | Junction plakoglobin | Common junctional plaque protein. |
| 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. |
| 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. |
| BAG3 | BAG family molecular chaperone regulator 3 | Co-chaperone and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g. |
Protein-family classification
Druggable: 3 · Difficult: 5 · Unknown: 6 · Druggable fraction: 0.21
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 | 8.0× | 0.198 |
| Antibody/Immunoglobulin | 2 | 4.2× | 0.198 |
| Scaffold/PPI | 3 | 3.7× | 0.198 |
| Transcription factor | 2 | 1.2× | 0.649 |
| Other/Unknown | 6 | 0.8× | 0.893 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| DTNA | Transcription factor | no | Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1 | |
| SCN5A | Ion channel | yes | Na_channel_asu, Ion_trans_dom, Na_channel_a5su | |
| ACTC1 | Other/Unknown | no | Actin, Actin_CS, Actin/actin-like_CS | |
| LDB3 | Transcription factor | no | PDZ, Znf_LIM, Zasp-like_motif | |
| ACTN2 | Other/Unknown | no | Actinin_actin-bd_CS, CH_dom, Spectrin_repeat | |
| MYPN | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, Ig-like_dom | |
| GJD2-DT | Other/Unknown | no | ||
| DTNA-AS1 | Other/Unknown | no | ||
| JUP | Other/Unknown | no | Armadillo, ARM-like, Beta-catenin | |
| MYBPC3 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| MYH6 | 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 | |
| BAG3 | Scaffold/PPI | no | WW_dom, BAG_domain, WW_dom_sf |
Expression context
Cohort genes with no expression data: 0.
10 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) | 14 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| apex of heart | 6 |
| hindlimb stylopod muscle | 4 |
| skeletal muscle tissue of biceps brachii | 3 |
| heart left ventricle | 2 |
| heart right ventricle | 2 |
| left ventricle myocardium | 2 |
| skeletal muscle tissue of rectus abdominis | 2 |
| gastrocnemius | 2 |
| right atrium auricular region | 2 |
| cardiac atrium | 2 |
| C1 segment of cervical spinal cord | 1 |
| globus pallidus | 1 |
| medial globus pallidus | 1 |
| cardiac ventricle | 1 |
| myocardium | 1 |
| vastus lateralis | 1 |
| corpus callosum | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| vermiform appendix | 1 |
| lower esophagus mucosa | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| DTNA | 266 | ubiquitous | marker | medial globus pallidus, globus pallidus, C1 segment of cervical spinal cord |
| SCN5A | 161 | broad | yes | apex of heart, heart left ventricle, cardiac ventricle |
| ACTC1 | 224 | broad | marker | left ventricle myocardium, heart right ventricle, myocardium |
| LDB3 | 247 | broad | marker | skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart |
| 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 |
| GJD2-DT | 114 | yes | right atrium auricular region, apex of heart, heart left ventricle | |
| DTNA-AS1 | 98 | yes | male germ line stem cell (sensu Vertebrata) in testis, corpus callosum, vermiform appendix | |
| JUP | 287 | ubiquitous | marker | lower esophagus mucosa, skin of leg, skin of abdomen |
| 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 |
| 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 |
| BAG3 | 286 | ubiquitous | marker | gastrocnemius, skeletal muscle tissue of rectus abdominis, body of tongue |
Protein interactions among cohort
Intra-cohort edges: 13.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| BAG3 | 4,957 |
| JUP | 4,618 |
| MYH6 | 3,119 |
| ACTN2 | 2,781 |
| MYH7 | 2,744 |
| SCN5A | 2,090 |
| PKP2 | 1,861 |
| MYBPC3 | 1,800 |
| MYPN | 1,764 |
| DTNA | 1,738 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ACTC1 | MYBPC3 | intact |
| 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 |
| BAG3 | LDB3 | string_interaction |
| JUP | PKP2 | string_interaction |
| LDB3 | MYBPC3 | string_interaction |
| LDB3 | MYH7 | string_interaction |
| LDB3 | MYPN | intact |
| MYBPC3 | MYH6 | string_interaction |
| MYBPC3 | MYH7 | intact, string_interaction |
| PKP2 | SCN5A | string_interaction |
Structural data
PDB: 9 · AlphaFold-only: 3 · No structure: 2
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| MYH7 | P12883 | 43 |
| MYBPC3 | Q14896 | 17 |
| SCN5A | Q14524 | 16 |
| ACTC1 | P68032 | 16 |
| ACTN2 | P35609 | 16 |
| LDB3 | O75112 | 2 |
| DTNA | Q9Y4J8 | 1 |
| JUP | P14923 | 1 |
| PKP2 | Q99959 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| MYH6 | P13533 | 74.91 |
| BAG3 | O95817 | 57.98 |
| MYPN | Q86TC9 | 52.71 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 60. Enrichment computed across 14 evidence-associated genes (9 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 9 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 | 4 | 137.2× | 7e-07 | ACTC1, ACTN2, MYBPC3, MYH6 |
| Muscle contraction | 5 | 42.9× | 1e-06 | SCN5A, ACTC1, ACTN2, MYBPC3, MYH6 |
| Regulation of CDH1 Function | 2 | 211.5× | 7e-04 | ACTC1, JUP |
| Formation of the dystrophin-glycoprotein complex (DGC) | 2 | 68.6× | 0.005 | DTNA, ACTC1 |
| Activation of STAT3 by cadherin engagement | 2 | 36.2× | 0.014 | ACTC1, JUP |
| RHOB GTPase cycle | 2 | 34.3× | 0.014 | ACTC1, JUP |
| Formation of the cornified envelope | 2 | 19.5× | 0.038 | JUP, PKP2 |
| CDH11 homotypic and heterotypic interactions | 1 | 181.3× | 0.038 | JUP |
| Regulation of CDH19 Expression and Function | 1 | 158.6× | 0.038 | JUP |
| RHOA GTPase cycle | 2 | 16.6× | 0.038 | ACTC1, JUP |
| Regulation of CDH11 function | 1 | 115.3× | 0.047 | JUP |
| CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 1 | 97.6× | 0.049 | ACTN2 |
| Keratinization | 2 | 12.4× | 0.049 | JUP, PKP2 |
| Ras activation upon Ca2+ influx through NMDA receptor | 1 | 63.4× | 0.059 | ACTN2 |
| Unblocking of NMDA receptors, glutamate binding and activation | 1 | 60.4× | 0.059 | ACTN2 |
| Negative regulation of NMDA receptor-mediated neuronal transmission | 1 | 60.4× | 0.059 | ACTN2 |
| SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST) | 1 | 55.2× | 0.059 | JUP |
| Nephrin family interactions | 1 | 52.9× | 0.059 | ACTN2 |
| Long-term potentiation | 1 | 52.9× | 0.059 | ACTN2 |
| VEGFR2 mediated vascular permeability | 1 | 45.3× | 0.065 | JUP |
| Cellular response to heat stress | 1 | 43.8× | 0.065 | BAG3 |
| Interaction between L1 and Ankyrins | 1 | 40.9× | 0.066 | SCN5A |
| Phase 0 - rapid depolarisation | 1 | 38.5× | 0.066 | SCN5A |
| Regulation of CDH1 posttranslational processing and trafficking to plasma membrane | 1 | 37.3× | 0.066 | JUP |
| RHOH GTPase cycle | 1 | 34.3× | 0.069 | JUP |
| Assembly and cell surface presentation of NMDA receptors | 1 | 28.2× | 0.079 | ACTN2 |
| Adherens junctions interactions | 1 | 27.6× | 0.079 | JUP |
| Post NMDA receptor activation events | 1 | 22.7× | 0.090 | ACTN2 |
| RHOJ GTPase cycle | 1 | 22.3× | 0.090 | JUP |
| Degradation of CDH1 | 1 | 21.9× | 0.090 | JUP |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 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 | 5 | 167.2× | 5e-09 | SCN5A, ACTC1, MYBPC3, MYH6, MYH7 |
| sarcomere organization | 5 | 159.6× | 5e-09 | LDB3, ACTN2, MYPN, MYBPC3, MYH6 |
| ventricular cardiac muscle tissue morphogenesis | 4 | 234.1× | 7e-08 | MYBPC3, MYH6, MYH7, PKP2 |
| striated muscle contraction | 3 | 210.7× | 1e-05 | DTNA, MYH6, MYH7 |
| regulation of heart rate | 3 | 117.0× | 5e-05 | SCN5A, MYH6, MYH7 |
| regulation of heart rate by cardiac conduction | 3 | 93.6× | 9e-05 | SCN5A, JUP, PKP2 |
| desmosome assembly | 2 | 401.2× | 2e-04 | JUP, PKP2 |
| bundle of His cell-Purkinje myocyte adhesion involved in cell communication | 2 | 401.2× | 2e-04 | JUP, PKP2 |
| regulation of ventricular cardiac muscle cell action potential | 2 | 234.1× | 5e-04 | JUP, PKP2 |
| adult heart development | 2 | 200.6× | 6e-04 | MYH6, MYH7 |
| regulation of cardiac muscle cell contraction | 2 | 187.2× | 6e-04 | SCN5A, MYBPC3 |
| cardiac muscle hypertrophy in response to stress | 2 | 175.5× | 6e-04 | MYH6, MYH7 |
| muscle filament sliding | 2 | 175.5× | 6e-04 | MYH6, MYH7 |
| regulation of the force of heart contraction | 2 | 165.2× | 6e-04 | MYH6, MYH7 |
| ventricular cardiac muscle cell action potential | 2 | 165.2× | 6e-04 | SCN5A, PKP2 |
| positive regulation of sodium ion transport | 2 | 140.4× | 8e-04 | SCN5A, PKP2 |
| cardiac muscle cell action potential involved in contraction | 2 | 117.0× | 0.001 | SCN5A, PKP2 |
| cardiac muscle cell development | 2 | 104.0× | 0.001 | ACTN2, MYH6 |
| protein localization to plasma membrane | 3 | 27.2× | 0.001 | ACTN2, JUP, PKP2 |
| ATP metabolic process | 2 | 78.0× | 0.002 | MYH6, MYH7 |
| positive regulation of protein import into nucleus | 2 | 70.2× | 0.002 | JUP, BAG3 |
| visceral muscle development | 1 | 1404.3× | 0.004 | MYH6 |
| striated muscle cell apoptotic process | 1 | 1404.3× | 0.004 | BAG3 |
| actin filament uncapping | 1 | 1404.3× | 0.004 | ACTN2 |
| maintenance of protein localization at cell tip | 1 | 1404.3× | 0.004 | PKP2 |
| regulation of slow-twitch skeletal muscle fiber contraction | 1 | 702.2× | 0.006 | MYH7 |
| regulation of muscle filament sliding | 1 | 702.2× | 0.006 | MYBPC3 |
| actin-myosin filament sliding | 1 | 702.2× | 0.006 | ACTC1 |
| regulation of heart growth | 1 | 702.2× | 0.006 | MYH6 |
| bundle of His cell action potential | 1 | 702.2× | 0.006 | SCN5A |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 13
Druggability breadth: 6 of 14 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 |
|---|---|
| SCN5A | BEPRIDIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SCN5A | 108 | 4 |
| DTNA | 0 | 0 |
| ACTC1 | 0 | 0 |
| LDB3 | 0 | 0 |
| ACTN2 | 0 | 0 |
| MYPN | 0 | 0 |
| GJD2-DT | 0 | 0 |
| DTNA-AS1 | 0 | 0 |
| JUP | 0 | 0 |
| MYBPC3 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| BEPRIDIL | 4 | SCN5A |
| CANDESARTAN CILEXETIL | 4 | SCN5A |
| TELMISARTAN | 4 | SCN5A |
| CARBAMAZEPINE | 4 | SCN5A |
| DIBUCAINE | 4 | SCN5A |
| IMIPRAMINE | 4 | SCN5A |
| DROPERIDOL | 4 | SCN5A |
| PONATINIB | 4 | SCN5A |
| DULOXETINE | 4 | SCN5A |
| PALONOSETRON | 4 | SCN5A |
| VILANTEROL | 4 | SCN5A |
| MEXILETINE HYDROCHLORIDE | 4 | SCN5A |
| UNOPROSTONE ISOPROPYL | 4 | SCN5A |
| LURASIDONE | 4 | SCN5A |
| LETERMOVIR | 4 | SCN5A |
| SERTINDOLE | 4 | SCN5A |
| FEDRATINIB | 4 | SCN5A |
| QUINIDINE | 4 | SCN5A |
| DARUNAVIR | 4 | SCN5A |
| DARIFENACIN | 4 | SCN5A |
| BENZONATATE | 4 | SCN5A |
| TOLTERODINE | 4 | SCN5A |
| RANOLAZINE | 4 | SCN5A |
| PIMOZIDE | 4 | SCN5A |
| NIMODIPINE | 4 | SCN5A |
| FELODIPINE | 4 | SCN5A |
| NICARDIPINE | 4 | SCN5A |
| AMLODIPINE | 4 | SCN5A |
| PHENYTOIN | 4 | SCN5A |
| PALIPERIDONE | 4 | SCN5A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SCN5A | 594 | Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1 |
| BAG3 | 8 | Binding:8 |
| ACTC1 | 6 | Binding:6 |
| JUP | 1 | Binding:1 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| SCN5A | 594 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 12; 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) |
|---|---|---|
| BEPRIDIL | 4 | SCN5A |
| CANDESARTAN CILEXETIL | 4 | SCN5A |
| TELMISARTAN | 4 | SCN5A |
| CARBAMAZEPINE | 4 | SCN5A |
| DIBUCAINE | 4 | SCN5A |
| IMIPRAMINE | 4 | SCN5A |
| DROPERIDOL | 4 | SCN5A |
| PONATINIB | 4 | SCN5A |
| DULOXETINE | 4 | SCN5A |
| PALONOSETRON | 4 | SCN5A |
| VILANTEROL | 4 | SCN5A |
| MEXILETINE HYDROCHLORIDE | 4 | SCN5A |
| UNOPROSTONE ISOPROPYL | 4 | SCN5A |
| LURASIDONE | 4 | SCN5A |
| LETERMOVIR | 4 | SCN5A |
| SERTINDOLE | 4 | SCN5A |
| FEDRATINIB | 4 | SCN5A |
| QUINIDINE | 4 | SCN5A |
| DARUNAVIR | 4 | SCN5A |
| DARIFENACIN | 4 | SCN5A |
| BENZONATATE | 4 | SCN5A |
| TOLTERODINE | 4 | SCN5A |
| RANOLAZINE | 4 | SCN5A |
| PIMOZIDE | 4 | SCN5A |
| NIMODIPINE | 4 | SCN5A |
| FELODIPINE | 4 | SCN5A |
| NICARDIPINE | 4 | SCN5A |
| AMLODIPINE | 4 | SCN5A |
| PHENYTOIN | 4 | SCN5A |
| PALIPERIDONE | 4 | SCN5A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | SCN5A |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | MYBPC3 |
| D | Druggable family + AlphaFold only, no drug | 1 | MYPN |
| E | Difficult family or no structure, no drug | 11 | DTNA, ACTC1, LDB3, ACTN2, GJD2-DT, DTNA-AS1, JUP, MYH6, MYH7, PKP2 (+1 more) |
Undrugged target profiles
13 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PKP2 | 0 | SCN5A |
| DTNA | 0 | — |
| ACTC1 | 6 | — |
| LDB3 | 0 | — |
| ACTN2 | 0 | — |
| MYPN | 0 | — |
| GJD2-DT | 0 | — |
| DTNA-AS1 | 0 | — |
| JUP | 1 | — |
| MYBPC3 | 0 | — |
| MYH6 | 0 | — |
| MYH7 | 0 | — |
| BAG3 | 8 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.