long QT syndrome 12

Summary

long QT syndrome 12 (MONDO:0013062) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 114

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	long QT syndrome 12
Mondo ID	MONDO:0013062
MeSH	C567842
OMIM	612955
DOID	DOID:0110653
UMLS	C2751830
MedGen	442824
GARD	0015595
Is cancer (heuristic)	no

Also known as: long QT syndrome 12 · long QT syndrome caused by mutation in SNTA1 · long QT syndrome type 12 · LQT12 · SNTA1 long QT syndrome

Data availability: 114 ClinVar variants · 2 GenCC gene-disease records · 4 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 12

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 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

114 retrieved; paginated sample, class counts are floors:

60 uncertain significance, 33 conflicting classifications of pathogenicity, 12 benign/likely benign, 7 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
190907	NM_003098.3(SNTA1):c.287G>C (p.Gly96Ala)	LOC130065679	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190903	NM_003098.3(SNTA1):c.128G>A (p.Ser43Asn)	LOC130065680	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190932	NM_003098.3(SNTA1):c.40G>A (p.Glu14Lys)	LOC130065680	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
496194	NM_003098.3(SNTA1):c.101G>A (p.Ser34Asn)	LOC130065680	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
894981	NM_003098.3(SNTA1):c.115G>A (p.Val39Met)	LOC130065680	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1023617	NM_003098.3(SNTA1):c.1340G>A (p.Arg447Gln)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1502599	NM_003098.3(SNTA1):c.419G>C (p.Gly140Ala)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1510952	NM_003098.3(SNTA1):c.1309G>A (p.Glu437Lys)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180528	NM_003098.3(SNTA1):c.784A>C (p.Thr262Pro)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188145	NM_003098.3(SNTA1):c.1442C>T (p.Ser481Leu)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190909	NM_003098.3(SNTA1):c.526T>C (p.Phe176Leu)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190914	NM_003098.3(SNTA1):c.787G>T (p.Ala263Ser)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190918	NM_003098.3(SNTA1):c.1088A>C (p.Glu363Ala)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190930	NM_003098.3(SNTA1):c.440C>A (p.Thr147Asn)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190934	NM_003098.3(SNTA1):c.160G>C (p.Gly54Arg)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190935	NM_003098.3(SNTA1):c.556G>A (p.Gly186Ser)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191548	NM_003098.3(SNTA1):c.770C>G (p.Ala257Gly)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
263476	NM_003098.3(SNTA1):c.221C>T (p.Pro74Leu)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
263623	NM_003098.3(SNTA1):c.566C>T (p.Ser189Leu)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
264288	NM_003098.3(SNTA1):c.619C>T (p.Arg207Trp)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
264348	NM_003098.3(SNTA1):c.620G>A (p.Arg207Gln)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
338209	NM_003098.3(SNTA1):c.*79C>A	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
338211	NM_003098.3(SNTA1):c.1479C>T (p.Phe493=)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
338212	NM_003098.3(SNTA1):c.1238-13G>C	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
378629	NM_003098.3(SNTA1):c.210G>C (p.Pro70=)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
449724	NM_003098.3(SNTA1):c.1388T>G (p.Leu463Arg)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
617899	NM_003098.3(SNTA1):c.770C>T (p.Ala257Val)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8476	NM_003098.3(SNTA1):c.1169C>T (p.Ala390Val)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
894980	NM_003098.3(SNTA1):c.312C>A (p.Gly104=)	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
896365	NM_003098.3(SNTA1):c.1238-14T>C	SNTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 4 · 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
SNTA1	Limited	Autosomal dominant	long QT syndrome 12	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SNTA1	Orphanet:101016	Romano-Ward syndrome
P3H1	Orphanet:216804	Osteogenesis imperfecta type 2
P3H1	Orphanet:216812	Osteogenesis imperfecta type 3
KCNC2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SNTA1	HGNC:11167	ENSG00000101400	Q13424	Alpha-1-syntrophin	gencc,clinvar
P3H1	HGNC:19316	ENSG00000117385	Q32P28	Prolyl 3-hydroxylase 1	clinvar
KCNC2	HGNC:6234	ENSG00000166006	Q96PR1	Voltage-gated potassium channel KCNC2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SNTA1	Alpha-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
P3H1	Prolyl 3-hydroxylase 1	Basement membrane-associated chondroitin sulfate proteoglycan (CSPG).
KCNC2	Voltage-gated potassium channel KCNC2	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.67

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	37.2×	0.080
Scaffold/PPI	1	5.8×	0.230
Enzyme (other)	1	4.0×	0.230

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SNTA1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
P3H1	Enzyme (other)	yes	1.14.11.28	Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph, TPR-like_helical_dom_sf
KCNC2	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1
adenohypophysis	1
stromal cell of endometrium	1
tibial nerve	1
Brodmann (1909) area 9	1
anterior cingulate cortex	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SNTA1	266	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius
P3H1	237	ubiquitous	marker	stromal cell of endometrium, adenohypophysis, tibial nerve
KCNC2	69	tissue_specific	marker	prefrontal cortex, Brodmann (1909) area 9, anterior cingulate cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNC2	2,436
SNTA1	1,499
P3H1	1,317

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
P3H1	Q32P28	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SNTA1	Q13424	80.00
KCNC2	Q96PR1	68.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the dystrophin-glycoprotein complex (DGC)	1	102.9×	0.030	SNTA1
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	88.5×	0.030	KCNC2
Voltage gated Potassium channels	1	81.0×	0.030	KCNC2
Regulation of insulin secretion	1	73.2×	0.030	KCNC2
Integration of energy metabolism	1	58.6×	0.030	KCNC2
Collagen biosynthesis and modifying enzymes	1	56.8×	0.030	P3H1
Non-integrin membrane-ECM interactions	1	51.4×	0.030	SNTA1
Potassium Channels	1	44.8×	0.030	KCNC2
Extracellular matrix organization	1	21.0×	0.057	SNTA1
Neuronal System	1	14.8×	0.073	KCNC2
Metabolism	1	3.9×	0.237	KCNC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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 action potential firing rate	1	1872.4×	0.005	KCNC2
response to nerve growth factor	1	1872.4×	0.005	KCNC2
negative regulation of post-translational protein modification	1	1404.3×	0.005	P3H1
protein hydroxylation	1	1123.5×	0.005	P3H1
globus pallidus development	1	1123.5×	0.005	KCNC2
cellular response to ammonium ion	1	1123.5×	0.005	KCNC2
response to kainic acid	1	802.5×	0.005	KCNC2
response to light intensity	1	702.2×	0.005	KCNC2
response to amine	1	624.1×	0.005	KCNC2
membrane hyperpolarization	1	624.1×	0.005	KCNC2
nitric oxide-cGMP-mediated signaling	1	510.7×	0.005	KCNC2
regulation of protein secretion	1	510.7×	0.005	P3H1
response to magnesium ion	1	468.1×	0.005	KCNC2
cellular response to toxic substance	1	468.1×	0.005	KCNC2
optic nerve development	1	401.2×	0.005	KCNC2
regulation of ossification	1	401.2×	0.005	P3H1
collagen metabolic process	1	351.1×	0.005	P3H1
protein heterooligomerization	1	351.1×	0.005	KCNC2
regulation of sodium ion transmembrane transport	1	351.1×	0.005	SNTA1
ventricular cardiac muscle cell action potential	1	330.4×	0.005	SNTA1
positive regulation of potassium ion transmembrane transport	1	330.4×	0.005	KCNC2
cellular response to nitric oxide	1	312.1×	0.006	KCNC2
regulation of ventricular cardiac muscle cell membrane repolarization	1	280.9×	0.006	SNTA1
positive regulation of Rac protein signal transduction	1	216.1×	0.007	SNTA1
regulation of heart rate	1	156.0×	0.010	SNTA1
action potential	1	119.5×	0.012	KCNC2
bone development	1	92.1×	0.015	P3H1
collagen fibril organization	1	74.9×	0.018	P3H1
muscle contraction	1	69.3×	0.019	SNTA1
potassium ion transport	1	63.8×	0.020	KCNC2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SNTA1	0	0
P3H1	0	0
KCNC2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNC2	32	Binding:31, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
P3H1	1.14.11.28, 1.14.11.7	proline 3-hydroxylase, procollagen-proline 3-dioxygenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	P3H1
D	Druggable family + AlphaFold only, no drug	1	KCNC2
E	Difficult family or no structure, no drug	1	SNTA1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SNTA1	0	—
P3H1	0	—
KCNC2	32	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.