Atrial fibrillation, familial, 12

Summary

Atrial fibrillation, familial, 12 (MONDO:0013545) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 56

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 12
Mondo ID	MONDO:0013545
OMIM	614050
UMLS	C3279695
MedGen	481325
GARD	0015748
Is cancer (heuristic)	no

Also known as: ABCC9 familial atrial fibrillation · ATFB12 · atrial fibrillation, familial, 12 · atrial fibrillation, familial, type 12 · familial atrial fibrillation caused by mutation in ABCC9

Data availability: 56 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › cardiac rhythm disease › atrial fibrillation › familial atrial fibrillation › atrial fibrillation, familial, 12

Related subtypes (17): atrial fibrillation, familial, 3, atrial fibrillation, familial, 1, atrial fibrillation, familial, 2, atrial fibrillation, familial, 4, atrial fibrillation, familial, 5, atrial fibrillation, familial, 6, atrial fibrillation, familial, 7, atrial fibrillation, familial, 8, atrial fibrillation, familial, 9, atrial fibrillation, familial, 10, atrial fibrillation, familial, 11, atrial fibrillation, familial, 13, atrial fibrillation, familial, 14, atrial fibrillation, familial, 15, atrial fibrillation, familial, 18, atrial fibrillation, familial, 17, atrial fibrillation, familial, 16

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

56 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 21 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1163346	NM_020297.4(ABCC9):c.1129A>G (p.Ile377Val)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1303112	NM_020297.4(ABCC9):c.3061G>A (p.Glu1021Lys)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1741141	NM_020297.4(ABCC9):c.4512T>C (p.Ala1504=)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179983	NM_020297.4(ABCC9):c.4196dup (p.Ser1400fs)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191584	NM_020297.4(ABCC9):c.3594G>A (p.Met1198Ile)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197035	NM_020297.4(ABCC9):c.4512+777G>A	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228426	NM_020297.4(ABCC9):c.4512+765C>T	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
393177	NM_020297.4(ABCC9):c.2470C>T (p.Arg824Ter)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
451662	NM_020297.4(ABCC9):c.2080C>T (p.Arg694Ter)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45389	NM_020297.4(ABCC9):c.1603T>C (p.Tyr535His)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45395	NM_020297.4(ABCC9):c.1987C>T (p.Arg663Cys)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45423	NM_020297.4(ABCC9):c.918G>A (p.Leu306=)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464658	NM_020297.4(ABCC9):c.1979G>A (p.Arg660Gln)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
533282	NM_020297.4(ABCC9):c.2857G>A (p.Glu953Lys)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
546502	NM_020297.4(ABCC9):c.1012-2A>G	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
806848	NM_020297.4(ABCC9):c.1743G>A (p.Leu581=)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
834481	NM_020297.4(ABCC9):c.1828_1829del (p.Leu610fs)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
856369	NM_020297.4(ABCC9):c.4512+711G>A	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
860588	NM_020297.4(ABCC9):c.2928_2929dup (p.Met977fs)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177999	NM_020297.4(ABCC9):c.3669G>A (p.Thr1223=)	KCNJ8-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
192108	NM_020297.4(ABCC9):c.4512+746_4512+747insT	KCNJ8-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009218	NM_020297.4(ABCC9):c.2818G>T (p.Ala940Ser)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030958	NM_020297.4(ABCC9):c.3283C>T (p.Arg1095Cys)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035510	NM_020297.4(ABCC9):c.723G>T (p.Lys241Asn)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1399756	NM_020297.4(ABCC9):c.295T>A (p.Ser99Thr)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1421599	NM_020297.4(ABCC9):c.1657G>T (p.Ala553Ser)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1475938	NM_020297.4(ABCC9):c.1147C>T (p.Leu383Phe)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
162692	NM_020297.4(ABCC9):c.1012-7G>A	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1677655	NM_020297.4(ABCC9):c.4014del (p.Gly1339fs)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
179082	NM_020297.4(ABCC9):c.575G>A (p.Arg192Lys)	ABCC9	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · 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
ABCC9	Limited	Unknown	atrial fibrillation, familial, 12	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCC9	Orphanet:130	Brugada syndrome
ABCC9	Orphanet:1517	Cantú syndrome
ABCC9	Orphanet:154	Familial isolated dilated cardiomyopathy
ABCC9	Orphanet:334	Hereditary atrial fibrillation

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABCC9	HGNC:60	ENSG00000069431	O60706	ATP-binding cassette sub-family C member 9	gencc,clinvar
KCNJ8-AS1	HGNC:58193	ENSG00000256615		KCNJ8 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCC9	ATP-binding cassette sub-family C member 9	Subunit of ATP-sensitive potassium channels (KATP).

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCC9	Transporter	yes		ABCC8/9, ABCC9, ABC_transporter-like_ATP-bd
KCNJ8-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
small intestine	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCC9	195	broad	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
KCNJ8-AS1	83		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, small intestine

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC9	1,728
KCNJ8-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABCC9	O60706	81.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	5710.0×	0.002	ABCC9
ATP sensitive Potassium channels	1	2855.0×	0.002	ABCC9
Inwardly rectifying K+ channels	1	713.8×	0.006	ABCC9
ABC transporter disorders	1	439.2×	0.007	ABCC9
Ion homeostasis	1	203.9×	0.013	ABCC9
Disorders of transmembrane transporters	1	139.3×	0.013	ABCC9
Potassium Channels	1	134.3×	0.013	ABCC9
ABC-family protein mediated transport	1	121.5×	0.013	ABCC9
Cardiac conduction	1	108.8×	0.013	ABCC9
Muscle contraction	1	77.2×	0.017	ABCC9
Neuronal System	1	44.3×	0.027	ABCC9
Transport of small molecules	1	25.1×	0.043	ABCC9
Disease	1	13.1×	0.076	ABCC9

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
response to hydrogen sulfide	1	8426.0×	0.004	ABCC9
oxygen metabolic process	1	4213.0×	0.004	ABCC9
cellular response to chemical stress	1	2808.7×	0.004	ABCC9
reactive oxygen species biosynthetic process	1	1872.4×	0.004	ABCC9
cardiac conduction	1	1685.2×	0.004	ABCC9
cardiac muscle cell contraction	1	1685.2×	0.004	ABCC9
response to peptide	1	1123.5×	0.004	ABCC9
fatty acid oxidation	1	1053.2×	0.004	ABCC9
cellular response to potassium ion	1	1053.2×	0.004	ABCC9
response to ATP	1	991.3×	0.004	ABCC9
obsolete inorganic cation transmembrane transport	1	936.2×	0.004	ABCC9
cellular response to ATP	1	887.0×	0.004	ABCC9
negative regulation of blood pressure	1	648.1×	0.004	ABCC9
coronary vasculature development	1	624.1×	0.004	ABCC9
monoatomic cation transmembrane transport	1	624.1×	0.004	ABCC9
regulation of potassium ion transmembrane transport	1	624.1×	0.004	ABCC9
response to hydrogen peroxide	1	468.1×	0.005	ABCC9
ATP metabolic process	1	468.1×	0.005	ABCC9
cellular respiration	1	432.1×	0.005	ABCC9
fibroblast proliferation	1	391.9×	0.005	ABCC9
heart morphogenesis	1	374.5×	0.005	ABCC9
vasodilation	1	366.4×	0.005	ABCC9
potassium ion import across plasma membrane	1	366.4×	0.005	ABCC9
action potential	1	358.6×	0.005	ABCC9
response to estrogen	1	343.9×	0.005	ABCC9
response to activity	1	324.1×	0.005	ABCC9
skeletal muscle tissue development	1	290.6×	0.005	ABCC9
cellular response to xenobiotic stimulus	1	240.7×	0.006	ABCC9
cellular response to calcium ion	1	200.6×	0.007	ABCC9
transport across blood-brain barrier	1	179.3×	0.007	ABCC9

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCC9	PINACIDIL ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC9	5	4
KCNJ8-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PINACIDIL ANHYDROUS	4	ABCC9
GLYBURIDE	4	ABCC9
PROPAFENONE	4	ABCC9
CROMAKALIM	2	ABCC9
CLAMIKALANT	2	ABCC9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABCC9	61	Functional:46, Binding:15

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

5 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.

Compound	Max phase	Cohort target (bioactivity)
PINACIDIL ANHYDROUS	4	ABCC9
GLYBURIDE	4	ABCC9
PROPAFENONE	4	ABCC9
CROMAKALIM	2	ABCC9
CLAMIKALANT	2	ABCC9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC9
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	KCNJ8-AS1

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)
KCNJ8-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.