long QT syndrome 2
diseaseOn this page
Also known as long QT syndrome type 2Long QT syndrome, acquired, reduced susceptibility toLQT2
Summary
long QT syndrome 2 (MONDO:0013367) is a disease caused by KCNH2 (GenCC Definitive), with 10 cohort genes and 2 clinical trials. The dominant Reactome pathway is Phase 3 - rapid repolarisation (3 cohort genes).
At a glance
- Causal gene: KCNH2 (GenCC Definitive)
- Cohort genes: 10
- ClinVar variants: 464
- Clinical trials: 2
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | long QT syndrome 2 |
| Mondo ID | MONDO:0013367 |
| MeSH | C563614 |
| OMIM | 613688 |
| DOID | DOID:0110645 |
| NCIT | C137957 |
| UMLS | C3150943 |
| MedGen | 462293 |
| GARD | 0003285 |
| Is cancer (heuristic) | no |
Also known as: long QT syndrome 2 · long QT syndrome type 2 · Long QT syndrome, acquired, reduced susceptibility to · LQT2
Data availability: 464 ClinVar variants · 4 GenCC gene-disease records · 42 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › long QT syndrome › familial long QT syndrome › long QT syndrome 2
Related subtypes (18): Jervell and Lange-Nielsen syndrome, Andersen-Tawil syndrome, cardiac arrhythmia, ankyrin-B-related, Timothy syndrome, long QT syndrome 3, long QT syndrome 9, long QT syndrome 10, long QT syndrome 11, long QT syndrome 12, long QT syndrome 13, long QT syndrome 6, long QT syndrome 5, long QT syndrome 14, long QT syndrome 15, long QT syndrome 8, long QT syndrome 16, long QT syndrome 1, long QT syndrome 4
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
464 retrieved; paginated sample, class counts are floors:
154 uncertain significance, 118 conflicting classifications of pathogenicity, 81 pathogenic, 38 likely pathogenic, 35 pathogenic/likely pathogenic, 19 benign/likely benign, 10 benign, 9 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2680774 | NM_000080.4(CHRNE):c.345-2A>G | CHRNE | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1064605 | NM_000238.4(KCNH2):c.2399-28del | KCNH2 | Pathogenic | criteria provided, single submitter |
| 1076382 | NM_000238.4(KCNH2):c.817C>T (p.Arg273Ter) | KCNH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1178326 | NM_000238.4(KCNH2):c.1425C>A (p.Tyr475Ter) | KCNH2 | Pathogenic | criteria provided, single submitter |
| 1197726 | NM_000238.4(KCNH2):c.232G>A (p.Ala78Thr) | KCNH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1338861 | NM_000238.4(KCNH2):c.418del (p.Ser140fs) | KCNH2 | Pathogenic | criteria provided, single submitter |
| 1420193 | NM_000238.4(KCNH2):c.2743del (p.Ala915fs) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14420 | NM_000238.4(KCNH2):c.1682C>T (p.Ala561Val) | KCNH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14421 | NM_000238.4(KCNH2):c.1408A>G (p.Asn470Asp) | KCNH2 | Pathogenic | no assertion criteria provided |
| 14423 | NM_000238.4(KCNH2):c.1778T>G (p.Ile593Arg) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14424 | NM_000238.4(KCNH2):c.2464G>A (p.Val822Met) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14426 | NM_000238.4(KCNH2):c.1261del (p.Thr421fs) | KCNH2 | Pathogenic | criteria provided, single submitter |
| 14427 | NM_000238.4(KCNH2):c.1882G>A (p.Gly628Ser) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14428 | NM_000238.4(KCNH2):c.1744C>T (p.Arg582Cys) | KCNH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14429 | NM_000238.4(KCNH2):c.1714G>C (p.Gly572Arg) | KCNH2 | Pathogenic | no assertion criteria provided |
| 14430 | NM_000238.4(KCNH2):c.1468G>A (p.Ala490Thr) | KCNH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14431 | NM_000238.4(KCNH2):c.3003G>A (p.Trp1001Ter) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14432 | NM_000238.4(KCNH2):c.2453C>T (p.Ser818Leu) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14434 | NM_000238.4(KCNH2):c.193A>C (p.Thr65Pro) | KCNH2 | Pathogenic | no assertion criteria provided |
| 14435 | NM_000238.4(KCNH2):c.2255G>A (p.Arg752Gln) | KCNH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14444 | NM_000238.4(KCNH2):c.1672G>C (p.Ala558Pro) | KCNH2 | Pathogenic | no assertion criteria provided |
| 1527873 | NM_000238.4(KCNH2):c.1397A>C (p.Asp466Ala) | KCNH2 | Pathogenic | criteria provided, single submitter |
| 1527874 | NM_000238.4(KCNH2):c.2731_2756dup (p.Ser919fs) | KCNH2 | Pathogenic | criteria provided, single submitter |
| 1675096 | NM_000238.4(KCNH2):c.1582_1603del (p.Arg528fs) | KCNH2 | Pathogenic | criteria provided, single submitter |
| 180379 | NM_000238.4(KCNH2):c.685G>T (p.Glu229Ter) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 180383 | NM_000238.4(KCNH2):c.2230C>T (p.Arg744Ter) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1804945 | NM_000238.4(KCNH2):c.3099dup (p.Pro1034fs) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 188144 | NM_000238.4(KCNH2):c.2900dup (p.Pro968fs) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 200321 | NM_000238.4(KCNH2):c.1096C>T (p.Arg366Ter) | KCNH2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 200323 | NM_000238.4(KCNH2):c.1128G>A (p.Gln376=) | KCNH2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 9 · Orphanet: 24 · 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 |
|---|---|---|---|---|
| KCNH2 | Definitive | Autosomal dominant | long QT syndrome 2 | 8 |
| ALG10B | Limited | Unknown | long QT syndrome 2 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| KCNH2 | Orphanet:101016 | Romano-Ward syndrome |
| KCNH2 | Orphanet:51083 | Congenital short QT syndrome |
| 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 |
| SNTA1 | Orphanet:101016 | Romano-Ward syndrome |
| CHRNE | Orphanet:98913 | Postsynaptic congenital myasthenic syndrome |
| LRP12 | Orphanet:98897 | Oculopharyngodistal myopathy |
| AKAP9 | Orphanet:101016 | Romano-Ward syndrome |
| AKAP9 | Orphanet:130 | Brugada syndrome |
| KCNQ1 | Orphanet:101016 | Romano-Ward syndrome |
| KCNQ1 | Orphanet:334 | Hereditary atrial fibrillation |
| KCNQ1 | Orphanet:51083 | Congenital short QT syndrome |
| KCNQ1 | Orphanet:90647 | Jervell and Lange-Nielsen syndrome |
| MPL | Orphanet:3318 | Essential thrombocythemia |
| MPL | Orphanet:3319 | Congenital amegakaryocytic thrombocytopenia |
| MPL | Orphanet:397692 | Hereditary isolated aplastic anemia |
| MPL | Orphanet:71493 | Familial thrombocytosis |
| MPL | Orphanet:824 | Primary myelofibrosis |
Cohort genes → proteins
10 cohort genes, 10 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 10 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| KCNH2 | HGNC:6251 | ENSG00000055118 | Q12809 | Voltage-gated inwardly rectifying potassium channel KCNH2 | gencc,clinvar |
| ALG10B | HGNC:31088 | ENSG00000175548 | Q5I7T1 | Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase B | gencc |
| SCN5A | HGNC:10593 | ENSG00000183873 | Q14524 | Sodium channel protein type 5 subunit alpha | clinvar |
| SNTA1 | HGNC:11167 | ENSG00000101400 | Q13424 | Alpha-1-syntrophin | clinvar |
| CHRNE | HGNC:1966 | ENSG00000108556 | Q04844 | Acetylcholine receptor subunit epsilon | clinvar |
| ALG10 | HGNC:23162 | ENSG00000139133 | Q5BKT4 | Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase A | clinvar |
| LRP12 | HGNC:31708 | ENSG00000147650 | Q9Y561 | Low-density lipoprotein receptor-related protein 12 | clinvar |
| AKAP9 | HGNC:379 | ENSG00000127914 | Q99996 | A-kinase anchor protein 9 | clinvar |
| KCNQ1 | HGNC:6294 | ENSG00000053918 | P51787 | Potassium voltage-gated channel subfamily KQT member 1 | clinvar |
| MPL | HGNC:7217 | ENSG00000117400 | P40238 | Thrombopoietin receptor | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| KCNH2 | Voltage-gated inwardly rectifying potassium channel KCNH2 | Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. |
| ALG10B | Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase B | Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. |
| 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. |
| SNTA1 | Alpha-1-syntrophin | Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. |
| CHRNE | Acetylcholine receptor subunit epsilon | After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. |
| ALG10 | Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase A | Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. |
| LRP12 | Low-density lipoprotein receptor-related protein 12 | Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. |
| AKAP9 | A-kinase anchor protein 9 | Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. |
| KCNQ1 | Potassium voltage-gated channel subfamily KQT member 1 | Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon. |
| MPL | Thrombopoietin receptor | Receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation. |
Protein-family classification
Druggable: 5 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.5
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 | 3 | 33.5× | 4e-04 |
| Antibody/Immunoglobulin | 1 | 2.9× | 0.727 |
| Scaffold/PPI | 1 | 1.7× | 0.727 |
| Enzyme (other) | 1 | 1.2× | 0.727 |
| Other/Unknown | 4 | 0.7× | 0.907 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| KCNH2 | Ion channel | yes | PAS, cNMP-bd_dom, PAS-assoc_C | |
| ALG10B | Other/Unknown | no | Alg10 | |
| SCN5A | Ion channel | yes | Na_channel_asu, Ion_trans_dom, Na_channel_a5su | |
| SNTA1 | Scaffold/PPI | no | PDZ, PH_domain, PH-like_dom_sf | |
| CHRNE | Other/Unknown | no | Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel | |
| ALG10 | Enzyme (other) | yes | 2.4.1.256 | Alg10 |
| LRP12 | Other/Unknown | no | CUB_dom, LDrepeatLR_classA_rpt, LDLR_class-A_CS | |
| AKAP9 | Other/Unknown | no | ELK_dom, PACT_domain, AKAP9/Pericentrin | |
| KCNQ1 | Ion channel | yes | K_chnl_volt-dep_KCNQ, Ion_trans_dom, K_chnl_volt-dep_KCQN1 | |
| MPL | Antibody/Immunoglobulin | yes | Long_hematopoietin_rcpt_CS, FN3_dom, Ig-like_fold |
Expression context
Cohort genes with no expression data: 0.
6 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 10 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| apex of heart | 3 |
| cardiac atrium | 2 |
| right atrium auricular region | 2 |
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| cortical plate | 2 |
| calcaneal tendon | 1 |
| pigmented layer of retina | 1 |
| tibia | 1 |
| cardiac ventricle | 1 |
| heart left ventricle | 1 |
| gastrocnemius | 1 |
| hindlimb stylopod muscle | 1 |
| adenohypophysis | 1 |
| bone marrow cell | 1 |
| primordial germ cell in gonad | 1 |
| ganglionic eminence | 1 |
| stromal cell of endometrium | 1 |
| bronchial epithelial cell | 1 |
| jejunal mucosa | 1 |
| left adrenal gland | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| KCNH2 | 211 | broad | marker | apex of heart, right atrium auricular region, cardiac atrium |
| ALG10B | 223 | ubiquitous | yes | calcaneal tendon, pigmented layer of retina, tibia |
| SCN5A | 161 | broad | yes | apex of heart, heart left ventricle, cardiac ventricle |
| SNTA1 | 266 | ubiquitous | marker | apex of heart, hindlimb stylopod muscle, gastrocnemius |
| CHRNE | 162 | broad | yes | right atrium auricular region, cardiac atrium, adenohypophysis |
| ALG10 | 172 | ubiquitous | yes | primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell |
| LRP12 | 255 | ubiquitous | marker | stromal cell of endometrium, cortical plate, ganglionic eminence |
| AKAP9 | 292 | ubiquitous | marker | jejunal mucosa, bronchial epithelial cell, cortical plate |
| KCNQ1 | 132 | broad | marker | left adrenal gland cortex, left adrenal gland, right adrenal gland cortex |
| MPL | 166 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, mononuclear cell, monocyte |
Protein interactions among cohort
Intra-cohort edges: 10.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| AKAP9 | 3,537 |
| KCNQ1 | 3,235 |
| SCN5A | 2,090 |
| KCNH2 | 1,932 |
| SNTA1 | 1,499 |
| MPL | 1,039 |
| LRP12 | 920 |
| CHRNE | 896 |
| ALG10 | 638 |
| ALG10B | 509 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| AKAP9 | KCNH2 | string_interaction |
| AKAP9 | KCNQ1 | biogrid_interaction, intact, string_interaction |
| AKAP9 | SNTA1 | string_interaction |
| ALG10B | KCNH2 | biogrid_interaction, string_interaction |
| CHRNE | LRP12 | biogrid_interaction |
| KCNH2 | KCNQ1 | string_interaction |
| KCNH2 | SCN5A | string_interaction |
| KCNQ1 | SCN5A | string_interaction |
| LRP12 | MPL | biogrid_interaction |
| SCN5A | SNTA1 | biogrid_interaction, string_interaction |
Structural data
PDB: 5 · AlphaFold-only: 5 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KCNQ1 | P51787 | 28 |
| KCNH2 | Q12809 | 24 |
| SCN5A | Q14524 | 16 |
| CHRNE | Q04844 | 13 |
| MPL | P40238 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ALG10 | Q5BKT4 | 93.51 |
| ALG10B | Q5I7T1 | 93.14 |
| SNTA1 | Q13424 | 80.00 |
| LRP12 | Q9Y561 | 63.10 |
| AKAP9 | Q99996 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 53. Enrichment computed across 10 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Phase 3 - rapid repolarisation | 3 | 342.6× | 3e-06 | KCNH2, AKAP9, KCNQ1 |
| Cardiac conduction | 4 | 43.5× | 4e-05 | KCNH2, SCN5A, AKAP9, KCNQ1 |
| Muscle contraction | 4 | 30.9× | 9e-05 | KCNH2, SCN5A, AKAP9, KCNQ1 |
| Phase 2 - plateau phase | 2 | 152.3× | 1e-03 | AKAP9, KCNQ1 |
| Voltage gated Potassium channels | 2 | 48.6× | 0.008 | KCNH2, KCNQ1 |
| Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein | 2 | 41.5× | 0.009 | ALG10, ALG10B |
| Neuronal System | 3 | 13.3× | 0.009 | KCNH2, CHRNE, KCNQ1 |
| Potassium Channels | 2 | 26.9× | 0.016 | KCNH2, KCNQ1 |
| Highly sodium permeable postsynaptic acetylcholine nicotinic receptors | 1 | 163.1× | 0.036 | CHRNE |
| Presynaptic nicotinic acetylcholine receptors | 1 | 95.2× | 0.050 | CHRNE |
| Acetylcholine binding and downstream events | 1 | 81.6× | 0.050 | CHRNE |
| Postsynaptic nicotinic acetylcholine receptors | 1 | 81.6× | 0.050 | CHRNE |
| Asparagine N-linked glycosylation | 2 | 12.0× | 0.050 | ALG10, ALG10B |
| Platelet Aggregation (Plug Formation) | 1 | 43.9× | 0.085 | MPL |
| Metabolism of fat-soluble vitamins | 1 | 38.1× | 0.089 | LRP12 |
| Interaction between L1 and Ankyrins | 1 | 36.8× | 0.089 | SCN5A |
| Phase 0 - rapid depolarisation | 1 | 34.6× | 0.089 | SCN5A |
| Formation of the dystrophin-glycoprotein complex (DGC) | 1 | 30.9× | 0.094 | SNTA1 |
| Visual phototransduction | 1 | 25.9× | 0.095 | LRP12 |
| Centrosome maturation | 1 | 25.4× | 0.095 | AKAP9 |
| Oncogenic MAPK signaling | 1 | 24.8× | 0.095 | AKAP9 |
| Retinoid metabolism and transport | 1 | 24.8× | 0.095 | LRP12 |
| Signaling by BRAF and RAF1 fusions | 1 | 17.0× | 0.125 | AKAP9 |
| Loss of Nlp from mitotic centrosomes | 1 | 15.9× | 0.125 | AKAP9 |
| Loss of proteins required for interphase microtubule organization from the centrosome | 1 | 15.9× | 0.125 | AKAP9 |
| Non-integrin membrane-ECM interactions | 1 | 15.4× | 0.125 | SNTA1 |
| AURKA Activation by TPX2 | 1 | 15.2× | 0.125 | AKAP9 |
| Recruitment of mitotic centrosome proteins and complexes | 1 | 13.6× | 0.129 | AKAP9 |
| Regulation of PLK1 Activity at G2/M Transition | 1 | 12.7× | 0.129 | AKAP9 |
| Mitotic G2-G2/M phases | 1 | 12.7× | 0.129 | AKAP9 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| regulation of ventricular cardiac muscle cell membrane repolarization | 5 | 421.3× | 4e-11 | KCNH2, SCN5A, SNTA1, AKAP9, KCNQ1 |
| ventricular cardiac muscle cell action potential | 4 | 396.5× | 9e-09 | KCNH2, SCN5A, SNTA1, KCNQ1 |
| regulation of heart rate by cardiac conduction | 4 | 149.8× | 4e-07 | KCNH2, SCN5A, AKAP9, KCNQ1 |
| regulation of membrane repolarization | 3 | 388.9× | 1e-06 | KCNH2, AKAP9, KCNQ1 |
| cardiac muscle contraction | 3 | 120.4× | 4e-05 | KCNH2, SCN5A, KCNQ1 |
| regulation of atrial cardiac muscle cell membrane repolarization | 2 | 481.5× | 1e-04 | SCN5A, KCNQ1 |
| membrane depolarization during action potential | 2 | 337.0× | 2e-04 | KCNH2, SCN5A |
| membrane repolarization during action potential | 2 | 337.0× | 2e-04 | KCNH2, KCNQ1 |
| membrane repolarization during cardiac muscle cell action potential | 2 | 337.0× | 2e-04 | KCNH2, KCNQ1 |
| atrial cardiac muscle cell action potential | 2 | 337.0× | 2e-04 | SCN5A, KCNQ1 |
| membrane repolarization during ventricular cardiac muscle cell action potential | 2 | 337.0× | 2e-04 | KCNH2, KCNQ1 |
| potassium ion export across plasma membrane | 2 | 210.7× | 4e-04 | KCNH2, KCNQ1 |
| regulation of sodium ion transmembrane transport | 2 | 210.7× | 4e-04 | SCN5A, SNTA1 |
| positive regulation of potassium ion transmembrane transport | 2 | 198.3× | 4e-04 | KCNH2, KCNQ1 |
| dolichol-linked oligosaccharide biosynthetic process | 2 | 168.5× | 5e-04 | ALG10, ALG10B |
| potassium ion homeostasis | 2 | 153.2× | 6e-04 | KCNH2, KCNQ1 |
| membrane depolarization | 2 | 102.1× | 0.001 | SCN5A, CHRNE |
| regulation of heart rate | 2 | 93.6× | 0.001 | SCN5A, SNTA1 |
| potassium ion import across plasma membrane | 2 | 73.3× | 0.002 | KCNH2, KCNQ1 |
| cellular response to cAMP | 2 | 58.1× | 0.003 | AKAP9, KCNQ1 |
| gastrin-induced gastric acid secretion | 1 | 1685.2× | 0.003 | KCNQ1 |
| negative regulation of voltage-gated potassium channel activity | 1 | 1685.2× | 0.003 | KCNQ1 |
| basophil homeostasis | 1 | 1685.2× | 0.003 | MPL |
| protein N-linked glycosylation | 2 | 52.7× | 0.003 | ALG10, ALG10B |
| cellular response to xenobiotic stimulus | 2 | 48.1× | 0.004 | KCNH2, KCNQ1 |
| regulation of membrane potential | 2 | 46.2× | 0.004 | KCNH2, KCNQ1 |
| regulation of heart rate by hormone | 1 | 842.6× | 0.004 | KCNH2 |
| rhythmic behavior | 1 | 842.6× | 0.004 | KCNQ1 |
| corticosterone secretion | 1 | 842.6× | 0.004 | KCNQ1 |
| stomach development | 1 | 842.6× | 0.004 | KCNQ1 |
Therapeutics
Drug target analysis
Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 5
Druggability breadth: 5 of 10 evidence-associated genes (50%) 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 |
|---|---|
| KCNH2 | CETIRIZINE |
| SCN5A | BEPRIDIL |
| CHRNE | MECAMYLAMINE |
| KCNQ1 | AMBRISENTAN |
| MPL | LUSUTROMBOPAG |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| KCNH2 | 706 | 4 |
| SCN5A | 108 | 4 |
| KCNQ1 | 15 | 4 |
| CHRNE | 4 | 4 |
| MPL | 2 | 4 |
| ALG10B | 0 | 0 |
| SNTA1 | 0 | 0 |
| ALG10 | 0 | 0 |
| LRP12 | 0 | 0 |
| AKAP9 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| CETIRIZINE | 4 | KCNH2 |
| BEPRIDIL | 4 | KCNH2, SCN5A |
| BEXAROTENE | 4 | KCNH2 |
| CLOTRIMAZOLE | 4 | KCNH2 |
| MORICIZINE | 4 | KCNH2 |
| PROPIVERINE | 4 | KCNH2 |
| SUVOREXANT | 4 | KCNH2 |
| ACETOPHENAZINE | 4 | KCNH2 |
| DIBUCAINE | 4 | KCNH2, SCN5A |
| MESORIDAZINE | 4 | KCNH2 |
| NIRAPARIB | 4 | KCNH2 |
| BUPIVACAINE | 4 | KCNH2 |
| IMIPRAMINE | 4 | KCNH2, SCN5A |
| BIPERIDEN | 4 | KCNH2 |
| EPINASTINE | 4 | KCNH2 |
| HALOFANTRINE | 4 | KCNH2 |
| DROPERIDOL | 4 | KCNH2, SCN5A |
| RIMONABANT | 4 | KCNH2 |
| ALOSETRON | 4 | KCNH2 |
| ARIPIPRAZOLE | 4 | KCNH2 |
| AMOXAPINE | 4 | KCNH2 |
| IDARUBICIN | 4 | KCNH2 |
| DICYCLOMINE | 4 | KCNH2 |
| TELITHROMYCIN | 4 | KCNH2 |
| EZETIMIBE | 4 | KCNH2 |
| SAQUINAVIR | 4 | KCNH2 |
| VINCAMINE | 4 | KCNH2 |
| PONATINIB | 4 | KCNH2, SCN5A |
| DESLORATADINE | 4 | KCNH2 |
| PRUCALOPRIDE | 4 | KCNH2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| KCNH2 | 4,851 | Binding:3558, Toxicity:1071, Functional:169, ADMET:53 |
| SCN5A | 594 | Binding:380, Functional:98, ADMET:72, Toxicity:43, Unclassified:1 |
| KCNQ1 | 179 | Binding:96, Functional:64, ADMET:14, Toxicity:5 |
| CHRNE | 28 | Binding:26, Functional:2 |
| MPL | 23 | Functional:15, Binding:7, ADMET:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ALG10 | 2.4.1.256 | dolichyl-P-Glc:Glc2Man9GlcNAc2-PP-dolichol alpha-1,2-glucosyltransferase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| KCNH2 | 4,851 |
| SCN5A | 594 |
| KCNQ1 | 179 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 10; 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) |
|---|---|---|
| CETIRIZINE | 4 | KCNH2 |
| BEPRIDIL | 4 | KCNH2, SCN5A |
| BEXAROTENE | 4 | KCNH2 |
| CLOTRIMAZOLE | 4 | KCNH2 |
| MORICIZINE | 4 | KCNH2 |
| PROPIVERINE | 4 | KCNH2 |
| SUVOREXANT | 4 | KCNH2 |
| ACETOPHENAZINE | 4 | KCNH2 |
| DIBUCAINE | 4 | KCNH2, SCN5A |
| MESORIDAZINE | 4 | KCNH2 |
| NIRAPARIB | 4 | KCNH2 |
| BUPIVACAINE | 4 | KCNH2 |
| IMIPRAMINE | 4 | KCNH2, SCN5A |
| BIPERIDEN | 4 | KCNH2 |
| EPINASTINE | 4 | KCNH2 |
| HALOFANTRINE | 4 | KCNH2 |
| DROPERIDOL | 4 | KCNH2, SCN5A |
| RIMONABANT | 4 | KCNH2 |
| ALOSETRON | 4 | KCNH2 |
| ARIPIPRAZOLE | 4 | KCNH2 |
| AMOXAPINE | 4 | KCNH2 |
| IDARUBICIN | 4 | KCNH2 |
| DICYCLOMINE | 4 | KCNH2 |
| TELITHROMYCIN | 4 | KCNH2 |
| EZETIMIBE | 4 | KCNH2 |
| SAQUINAVIR | 4 | KCNH2 |
| VINCAMINE | 4 | KCNH2 |
| PONATINIB | 4 | KCNH2, SCN5A |
| DESLORATADINE | 4 | KCNH2 |
| PRUCALOPRIDE | 4 | KCNH2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 5 | KCNH2, SCN5A, CHRNE, KCNQ1, MPL |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | ALG10 |
| E | Difficult family or no structure, no drug | 4 | ALG10B, SNTA1, LRP12, AKAP9 |
Undrugged target profiles
5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| ALG10B | 0 | KCNH2 |
| SNTA1 | 0 | SCN5A |
| AKAP9 | 0 | KCNQ1 |
| ALG10 | 0 | — |
| LRP12 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 2.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| PHASE2/PHASE3 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT07277582 | PHASE2/PHASE3 | RECRUITING | Evaluation of Efficacy and Safety of THRV-1268 in Long QT Syndrome Type 2 (LQTS 2) |
| NCT07075445 | Not specified | RECRUITING | Observational Study to Describe Health-Related Quality of Life and Measure Disease Burden Among Patients With Long QT Syndrome Types (LQTS) 2 and 3 |