long QT syndrome 10

Summary

long QT syndrome 10 (MONDO:0012737) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 178

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	long QT syndrome 10
Mondo ID	MONDO:0012737
MeSH	C567514
OMIM	611819
DOID	DOID:0110651
UMLS	C2678484
MedGen	394836
GARD	0010436
Is cancer (heuristic)	no

Also known as: long QT syndrome 10 · long QT syndrome caused by mutation in SCN4B · long QT syndrome type 10 · LQT10 · SCN4B long QT syndrome

Data availability: 178 ClinVar variants · 3 GenCC gene-disease records.

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 10

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 11, 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

178 retrieved; paginated sample, class counts are floors:

96 uncertain significance, 56 likely benign, 18 conflicting classifications of pathogenicity, 6 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1365345	NM_174934.4(SCN4B):c.463C>T (p.Leu155=)	LOC126861356	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1484623	NM_174934.4(SCN4B):c.259G>A (p.Glu87Lys)	LOC126861356	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190893	NM_174934.4(SCN4B):c.235-18A>G	LOC126861356	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1331417	NM_174934.4(SCN4B):c.480C>G (p.Asn160Lys)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1745090	NM_174934.4(SCN4B):c.505G>A (p.Val169Ile)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1788256	NM_174934.4(SCN4B):c.223G>A (p.Ala75Thr)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190889	NM_174934.4(SCN4B):c.18C>A (p.Asp6Glu)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190890	NM_174934.4(SCN4B):c.22G>A (p.Gly8Ser)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190891	NM_174934.4(SCN4B):c.194A>T (p.His65Leu)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190895	NM_174934.4(SCN4B):c.632C>G (p.Thr211Arg)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191380	NM_174934.4(SCN4B):c.617C>T (p.Ser206Leu)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191497	NM_174934.4(SCN4B):c.112G>C (p.Ala38Pro)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191547	NM_174934.4(SCN4B):c.607G>A (p.Val203Met)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2702264	NM_174934.4(SCN4B):c.584G>A (p.Arg195Gln)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
302646	NM_174934.4(SCN4B):c.482C>G (p.Thr161Arg)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420671	NM_174934.4(SCN4B):c.542T>C (p.Leu181Pro)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
574219	NM_174934.4(SCN4B):c.520A>G (p.Ile174Val)	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
811996	NM_174934.4(SCN4B):c.62-16G>A	SCN4B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1211576	NM_174934.4(SCN4B):c.347T>C (p.Ile116Thr)	LOC126861356	Uncertain significance	criteria provided, multiple submitters, no conflicts
1363895	NM_174934.4(SCN4B):c.346del (p.Ile116fs)	LOC126861356	Uncertain significance	criteria provided, single submitter
1403433	NM_174934.4(SCN4B):c.272C>A (p.Pro91His)	LOC126861356	Uncertain significance	criteria provided, single submitter
1804895	NM_174934.4(SCN4B):c.377C>T (p.Thr126Met)	LOC126861356	Uncertain significance	criteria provided, single submitter
2085251	NM_174934.4(SCN4B):c.264G>T (p.Lys88Asn)	LOC126861356	Uncertain significance	criteria provided, multiple submitters, no conflicts
2166933	NM_174934.4(SCN4B):c.241_242delinsTT (p.Glu81Leu)	LOC126861356	Uncertain significance	criteria provided, single submitter
3022695	NM_174934.4(SCN4B):c.463+1G>A	LOC126861356	Uncertain significance	criteria provided, single submitter
452457	NM_174934.4(SCN4B):c.397G>A (p.Val133Met)	LOC126861356	Uncertain significance	criteria provided, multiple submitters, no conflicts
4696764	NM_174934.4(SCN4B):c.442T>C (p.Phe148Leu)	LOC126861356	Uncertain significance	criteria provided, multiple submitters, no conflicts
4698307	NM_174934.4(SCN4B):c.241G>A (p.Glu81Lys)	LOC126861356	Uncertain significance	criteria provided, single submitter
537383	NM_174934.4(SCN4B):c.376A>G (p.Thr126Ala)	LOC126861356	Uncertain significance	criteria provided, single submitter
637988	NM_174934.4(SCN4B):c.298C>T (p.Arg100Cys)	LOC126861356	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SCN4B	Limited	Unknown	long QT syndrome 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN4B	Orphanet:101016	Romano-Ward syndrome
SCN4B	Orphanet:334	Hereditary atrial fibrillation

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN4B	HGNC:10592	ENSG00000177098	Q8IWT1	Sodium channel regulatory subunit beta-4	gencc,clinvar
UPK2	HGNC:12579	ENSG00000110375	O00526	Uroplakin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN4B	Sodium channel regulatory subunit beta-4	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
UPK2	Uroplakin-2	Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · 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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN4B	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_dom
UPK2	Other/Unknown	no		Uroplakin-2

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	1
lateral globus pallidus	1
putamen	1
endometrium epithelium	1
lower esophagus mucosa	1
urinary bladder	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN4B	223	broad	marker	lateral globus pallidus, dorsal root ganglion, putamen
UPK2	120	broad	marker	endometrium epithelium, urinary bladder, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN4B	1,551
UPK2	829

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN4B	Q8IWT1	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UPK2	O00526	77.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 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
Interaction between L1 and Ankyrins	1	368.4×	0.010	SCN4B
Phase 0 - rapid depolarisation	1	346.1×	0.010	SCN4B
Sensory perception of taste	1	335.9×	0.010	SCN4B
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.010	SCN4B
L1CAM interactions	1	120.2×	0.017	SCN4B
Cardiac conduction	1	108.8×	0.017	SCN4B
Sensory Perception	1	95.2×	0.017	SCN4B
Muscle contraction	1	77.2×	0.018	SCN4B
Axon guidance	1	45.1×	0.026	SCN4B
Nervous system development	1	42.9×	0.026	SCN4B
Developmental Biology	1	14.5×	0.069	SCN4B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
AV node cell action potential	1	2106.5×	0.006	SCN4B
cardiac conduction	1	842.6×	0.006	SCN4B
membrane depolarization during cardiac muscle cell action potential	1	702.2×	0.006	SCN4B
positive regulation of sodium ion transport	1	421.3×	0.006	SCN4B
regulation of ventricular cardiac muscle cell membrane repolarization	1	421.3×	0.006	SCN4B
cardiac muscle cell action potential involved in contraction	1	351.1×	0.006	SCN4B
neuronal action potential	1	240.7×	0.008	SCN4B
cardiac muscle contraction	1	200.6×	0.008	SCN4B
regulation of heart rate by cardiac conduction	1	187.2×	0.008	SCN4B
sodium ion transport	1	135.9×	0.010	SCN4B
sodium ion transmembrane transport	1	101.5×	0.012	SCN4B
epithelial cell differentiation	1	87.8×	0.012	UPK2
establishment of localization in cell	1	80.2×	0.012	SCN4B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
SCN4B	0	0
UPK2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	SCN4B
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	UPK2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SCN4B	0	—
UPK2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.