short QT syndrome 7

Summary

short QT syndrome 7 (MONDO:0859368) is a disease caused by SLC4A3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC4A3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short QT syndrome 7
Mondo ID	MONDO:0859368
OMIM	620231
UMLS	C5774304
MedGen	1824077
GARD	0026720
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart conduction disease › short QT syndrome › short QT syndrome 7

Related subtypes (3): short QT syndrome type 1, short QT syndrome type 2, short QT syndrome type 3

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

6 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443882	NM_005070.4(SLC4A3):c.1028G>A (p.Arg343His)	SLC4A3	Pathogenic	no assertion criteria provided
3374734	NM_005070.4(SLC4A3):c.1027C>T (p.Arg343Cys)	SLC4A3	Likely pathogenic	criteria provided, single submitter
2203804	NM_005070.4(SLC4A3):c.1781G>A (p.Arg594Gln)	SLC4A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2259640	NM_005070.4(SLC4A3):c.2330C>G (p.Ala777Gly)	SLC4A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2665088	NM_005070.4(SLC4A3):c.1456A>G (p.Lys486Glu)	SLC4A3	Uncertain significance	criteria provided, single submitter
3255062	NM_005070.4(SLC4A3):c.1486G>A (p.Asp496Asn)	SLC4A3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
SLC4A3	Strong	Autosomal dominant	short QT syndrome 7	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC4A3	Orphanet:51083	Congenital short QT 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
SLC4A3	HGNC:11029	ENSG00000114923	P48751	Anion exchange protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC4A3	Anion exchange protein 3	Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane.

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)
SLC4A3	Other/Unknown	no		Anion_exchange, Anion_exchange_3, HCO3_transpt_euk

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
apex of heart	1
cardiac atrium	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC4A3	203	ubiquitous	marker	apex of heart, right atrium auricular region, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC4A3	859

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC4A3	P48751	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Bicarbonate transporters	1	1142.0×	0.004	SLC4A3
R-HSA-425393	1	129.8×	0.015	SLC4A3
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC4A3
Transport of small molecules	1	25.1×	0.040	SLC4A3

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
cardiac muscle cell action potential	1	8426.0×	9e-04	SLC4A3
regulation of cardiac muscle cell action potential	1	2808.7×	0.001	SLC4A3
pH reduction	1	2407.4×	0.001	SLC4A3
cardiac conduction	1	1685.2×	0.001	SLC4A3
bicarbonate transport	1	802.5×	0.002	SLC4A3
regulation of intracellular pH	1	601.9×	0.002	SLC4A3
transport across blood-brain barrier	1	179.3×	0.006	SLC4A3
transmembrane transport	1	168.5×	0.006	SLC4A3

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
SLC4A3	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	SLC4A3

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)
SLC4A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.