long QT syndrome 11

Summary

long QT syndrome 11 (MONDO:0012738) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 294

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	long QT syndrome 11
Mondo ID	MONDO:0012738
MeSH	C567513
OMIM	611820
DOID	DOID:0110652
UMLS	C2678483
MedGen	437218
GARD	0010437
Is cancer (heuristic)	no

Also known as: AKAP9 long QT syndrome · long QT syndrome 11 · long QT syndrome caused by mutation in AKAP9 · long QT syndrome type 11 · LQT11

Data availability: 294 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

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 11

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 12, long QT syndrome 13, long QT syndrome 2, 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

294 retrieved; paginated sample, class counts are floors:

110 uncertain significance, 84 conflicting classifications of pathogenicity, 76 benign/likely benign, 12 benign, 10 likely benign, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
180261	NM_005751.5(AKAP9):c.1489G>T (p.Glu497Ter)	AKAP9	Likely pathogenic	no assertion criteria provided
4687971	NM_005751.5(AKAP9):c.571C>T (p.Gln191Ter)	AKAP9	Likely pathogenic	criteria provided, single submitter
1000463	NM_005751.5(AKAP9):c.6970A>G (p.Ile2324Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1005329	NM_005751.5(AKAP9):c.6676G>A (p.Val2226Ile)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1008534	NM_005751.5(AKAP9):c.8783G>A (p.Arg2928Gln)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015297	NM_005751.5(AKAP9):c.11231G>C (p.Gly3744Ala)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1023062	NM_005751.5(AKAP9):c.4598G>A (p.Ser1533Asn)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027262	NM_005751.5(AKAP9):c.4331T>C (p.Val1444Ala)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1035224	NM_005751.5(AKAP9):c.3793G>A (p.Glu1265Lys)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1052653	NM_005751.5(AKAP9):c.7114A>G (p.Met2372Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1284437	NM_005751.5(AKAP9):c.5680A>G (p.Lys1894Glu)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1284691	NM_005751.5(AKAP9):c.8747C>A (p.Thr2916Lys)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1370771	NM_005751.5(AKAP9):c.8112A>C (p.Glu2704Asp)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1400985	NM_005751.5(AKAP9):c.8314A>G (p.Ile2772Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1401389	NM_005751.5(AKAP9):c.4282A>G (p.Ile1428Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1402564	NM_005751.5(AKAP9):c.3934A>C (p.Thr1312Pro)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1403513	NM_005751.5(AKAP9):c.6195G>A (p.Met2065Ile)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1403793	NM_005751.5(AKAP9):c.7363A>G (p.Ile2455Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1403962	NM_005751.5(AKAP9):c.9425G>T (p.Ser3142Ile)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1409000	NM_005751.5(AKAP9):c.8283C>T (p.Ser2761=)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1412647	NM_005751.5(AKAP9):c.3448C>T (p.Leu1150Phe)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1418465	NM_005751.5(AKAP9):c.7213G>A (p.Ala2405Thr)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1426673	NM_005751.5(AKAP9):c.10643T>C (p.Ile3548Thr)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1432317	NM_005751.5(AKAP9):c.2368A>G (p.Met790Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1462124	NM_005751.5(AKAP9):c.3864G>A (p.Met1288Ile)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1497491	NM_005751.5(AKAP9):c.11213C>T (p.Ala3738Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1505527	NM_005751.5(AKAP9):c.10315A>G (p.Ile3439Val)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1628099	NM_005751.5(AKAP9):c.3426T>C (p.Ala1142=)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1754722	NM_005751.5(AKAP9):c.665A>G (p.Asp222Gly)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180262	NM_005751.5(AKAP9):c.3580G>A (p.Ala1194Thr)	AKAP9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
AKAP9	Limited	Autosomal dominant	long QT syndrome 11	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AKAP9	Orphanet:101016	Romano-Ward syndrome
AKAP9	Orphanet:130	Brugada syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AKAP9	HGNC:379	ENSG00000127914	Q99996	A-kinase anchor protein 9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AKAP9	A-kinase anchor protein 9	Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AKAP9	Other/Unknown	no		ELK_dom, PACT_domain, AKAP9/Pericentrin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
cortical plate	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AKAP9	292	ubiquitous	marker	jejunal mucosa, bronchial epithelial cell, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AKAP9	3,537

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AKAP9	Q99996

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1	1142.0×	0.014	AKAP9
Phase 2 - plateau phase	1	761.3×	0.014	AKAP9
Centrosome maturation	1	253.8×	0.014	AKAP9
Oncogenic MAPK signaling	1	248.3×	0.014	AKAP9
Signaling by BRAF and RAF1 fusions	1	170.4×	0.014	AKAP9
Loss of Nlp from mitotic centrosomes	1	158.6×	0.014	AKAP9
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.014	AKAP9
AURKA Activation by TPX2	1	152.3×	0.014	AKAP9
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.014	AKAP9
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.014	AKAP9
Mitotic G2-G2/M phases	1	126.9×	0.014	AKAP9
G2/M Transition	1	126.9×	0.014	AKAP9
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.014	AKAP9
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	AKAP9
Cardiac conduction	1	108.8×	0.014	AKAP9
Cilium Assembly	1	108.8×	0.014	AKAP9
Muscle contraction	1	77.2×	0.018	AKAP9
Mitotic Prometaphase	1	69.2×	0.018	AKAP9
Organelle biogenesis and maintenance	1	66.0×	0.018	AKAP9
M Phase	1	66.0×	0.018	AKAP9
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.020	AKAP9
Cell Cycle, Mitotic	1	48.2×	0.023	AKAP9
Cell Cycle	1	36.0×	0.029	AKAP9
Disease	1	13.1×	0.076	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of centrosome location	1	2808.7×	0.002	AKAP9
regulation of cardiac muscle cell action potential involved in regulation of contraction	1	1872.4×	0.002	AKAP9
regulation of membrane repolarization	1	1296.3×	0.002	AKAP9
regulation of Golgi organization	1	1123.5×	0.002	AKAP9
protein-containing complex localization	1	991.3×	0.002	AKAP9
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.002	AKAP9
positive regulation of microtubule polymerization	1	674.1×	0.002	AKAP9
response to electrical stimulus	1	648.1×	0.002	AKAP9
microtubule nucleation	1	624.1×	0.002	AKAP9
regulation of heart rate by cardiac conduction	1	374.5×	0.003	AKAP9
cellular response to cAMP	1	290.6×	0.004	AKAP9
chemical synaptic transmission	1	77.3×	0.014	AKAP9
signal transduction	1	16.1×	0.062	AKAP9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AKAP9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AKAP9

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AKAP9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.