Atrial standstill 1

Summary

Atrial standstill 1 (MONDO:0007171) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 299

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial standstill 1
Mondo ID	MONDO:0007171
OMIM	108770
DOID	DOID:0080662
UMLS	C4551959
MedGen	1646392
GARD	0018611
Is cancer (heuristic)	no

Also known as: atrial standstill 1 · atrial standstill type 1 · atrial standstill, digenic (GJA5/SCN5A) · ATRST1

Data availability: 299 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › restrictive cardiomyopathy › familial restrictive cardiomyopathy › atrial standstill › atrial standstill 1

Related subtypes (1): atrial standstill 2

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

299 retrieved; paginated sample, class counts are floors:

193 uncertain significance, 90 likely benign, 8 conflicting classifications of pathogenicity, 3 pathogenic, 3 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1444016	NC_000001.10:g.(?147230270)(147231346_?)del	GJA5	Pathogenic	criteria provided, single submitter
2042319	NM_181703.4(GJA5):c.23del (p.Gly8fs)	GJA5	Pathogenic	criteria provided, single submitter
3755327	NM_181703.4(GJA5):c.3G>A (p.Met1Ile)	GJA5	Pathogenic	criteria provided, single submitter
2182825	NM_181703.4(GJA5):c.497G>C (p.Gly166Ala)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2639123	NM_181703.4(GJA5):c.932G>C (p.Gly311Ala)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292448	NM_181703.4(GJA5):c.995G>A (p.Arg332His)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292450	NM_181703.4(GJA5):c.353G>A (p.Arg118Gln)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292451	NM_181703.4(GJA5):c.342C>G (p.Ala114=)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292453	NM_181703.4(GJA5):c.13A>G (p.Ser5Gly)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
577662	NM_181703.4(GJA5):c.973A>C (p.Asn325His)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876990	NM_181703.4(GJA5):c.348G>A (p.Glu116=)	GJA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001932	NM_181703.4(GJA5):c.941A>G (p.Gln314Arg)	GJA5	Uncertain significance	criteria provided, single submitter
1018451	NM_181703.4(GJA5):c.199G>A (p.Asp67Asn)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034934	NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter)	GJA5	Uncertain significance	criteria provided, single submitter
1038988	NM_181703.4(GJA5):c.278T>C (p.Met93Thr)	GJA5	Uncertain significance	criteria provided, single submitter
1056660	NM_181703.4(GJA5):c.1024C>T (p.Arg342Ter)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1062702	NM_181703.4(GJA5):c.170T>G (p.Ile57Ser)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
126903	NM_181703.4(GJA5):c.223A>T (p.Ile75Phe)	GJA5	Uncertain significance	criteria provided, single submitter
1316153	NM_181703.4(GJA5):c.977G>C (p.Gly326Ala)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1316776	NM_181703.4(GJA5):c.53C>T (p.Ser18Leu)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1317232	NM_181703.4(GJA5):c.359C>G (p.Ser120Cys)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1317266	NM_181703.4(GJA5):c.724C>T (p.Arg242Trp)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1318650	NM_181703.4(GJA5):c.356G>A (p.Gly119Asp)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1345427	NM_181703.4(GJA5):c.893C>G (p.Thr298Ser)	GJA5	Uncertain significance	criteria provided, single submitter
1347734	NM_181703.4(GJA5):c.229T>C (p.Tyr77His)	GJA5	Uncertain significance	criteria provided, single submitter
1357441	NM_181703.4(GJA5):c.700A>T (p.Ile234Phe)	GJA5	Uncertain significance	criteria provided, single submitter
1358271	NM_181703.4(GJA5):c.304A>T (p.Met102Leu)	GJA5	Uncertain significance	criteria provided, single submitter
1365094	NM_181703.4(GJA5):c.526G>A (p.Gly176Arg)	GJA5	Uncertain significance	criteria provided, single submitter
1370893	NM_181703.4(GJA5):c.709C>T (p.Arg237Ter)	GJA5	Uncertain significance	criteria provided, single submitter
1380742	NM_181703.4(GJA5):c.1028G>A (p.Arg343His)	GJA5	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GJA5	Orphanet:3303	Tetralogy of Fallot
GJA5	Orphanet:334	Hereditary atrial fibrillation

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
GJA5	HGNC:4279	ENSG00000265107	P36382	Gap junction alpha-5 protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GJA5	Gap junction alpha-5 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

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)
GJA5	Other/Unknown	no		Connexin, Connexin40, Connexin_N

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
left coronary artery	1
placenta	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GJA5	190	broad	marker	placenta, right coronary artery, left coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GJA5	1,476

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GJA5	P36382	70.35

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Gap junction assembly	1	292.8×	0.003	GJA5

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
mitral valve development	1	16852.0×	3e-04	GJA5
septum primum development	1	16852.0×	3e-04	GJA5
atrial ventricular junction remodeling	1	16852.0×	3e-04	GJA5
positive regulation of cell communication by chemical coupling	1	16852.0×	3e-04	GJA5
atrial cardiac muscle cell to AV node cell communication by electrical coupling	1	16852.0×	3e-04	GJA5
Purkinje myocyte to ventricular cardiac muscle cell communication by electrical coupling	1	16852.0×	3e-04	GJA5
regulation of Purkinje myocyte action potential	1	16852.0×	3e-04	GJA5
regulation of renin secretion into blood stream	1	16852.0×	3e-04	GJA5
vasomotion	1	16852.0×	3e-04	GJA5
pulmonary valve formation	1	8426.0×	4e-04	GJA5
cell communication by chemical coupling	1	8426.0×	4e-04	GJA5
foramen ovale closure	1	8426.0×	4e-04	GJA5
SA node cell to atrial cardiac muscle cell communication by electrical coupling	1	8426.0×	4e-04	GJA5
AV node cell to bundle of His cell communication by electrical coupling	1	8426.0×	4e-04	GJA5
bundle of His cell to Purkinje myocyte communication by electrical coupling	1	8426.0×	4e-04	GJA5
regulation of bundle of His cell action potential	1	8426.0×	4e-04	GJA5
regulation of AV node cell action potential	1	5617.3×	5e-04	GJA5
regulation of atrial cardiac muscle cell action potential	1	5617.3×	5e-04	GJA5
negative regulation of glomerular filtration	1	4213.0×	6e-04	GJA5
regulation of membrane depolarization during cardiac muscle cell action potential	1	4213.0×	6e-04	GJA5
regulation of ventricular cardiac muscle cell membrane depolarization	1	2808.7×	8e-04	GJA5
SA node cell action potential	1	2808.7×	8e-04	GJA5
regulation of cell communication by electrical coupling	1	2407.4×	9e-04	GJA5
atrial septum development	1	2106.5×	9e-04	GJA5
gap junction assembly	1	2106.5×	9e-04	GJA5
regulation of atrial cardiac muscle cell membrane depolarization	1	1872.4×	1e-03	GJA5
cell communication by electrical coupling involved in cardiac conduction	1	1404.3×	0.001	GJA5
endothelium development	1	1296.3×	0.001	GJA5
atrial septum morphogenesis	1	1296.3×	0.001	GJA5
cardiac conduction system development	1	1053.2×	0.002	GJA5

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
GJA5	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	GJA5

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)
GJA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.