ABCC9

Chr 12ADAR

ATP binding cassette subfamily C member 9

Also known as: ABC37, ATFB12, CANTU, CMD1O, IDMYS, SUR2

NCBI Gene: 10060ENSG00000069431UniProt: O60706

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein is thought to form ATP-sensitive potassium channels in cardiac, skeletal, and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel-modulating subunit of the extra-pancreatic ATP-sensitive potassium channels. Mutations in this gene are associated with cardiomyopathy dilated type 1O. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2011]

Primary Disease Associations & Inheritance

?Atrial fibrillation, familial, 12MIM #614050
AD
Cardiomyopathy, dilated, 1OMIM #608569
AD
Hypertrichotic osteochondrodysplasia (Cantu syndrome)MIM #239850
AD
Intellectual disability and myopathy syndromeMIM #619719
AR
682
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ABCC9
🧬
Gene-Disease Validity (ClinGen)
hypertrichotic osteochondrodysplasia Cantu type · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

3 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 330 VUS of 682 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.000
Z-score 5.49
OE 0.36 (0.27–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.97Z-score
OE missense 0.52 (0.48–0.56)
432 obs / 836.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.27–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.48–0.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 30 / 84.4Missense obs/exp: 432 / 836.4Syn Z: 0.01

ClinVar Variant Classifications

682 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic8
VUS330
Likely Benign293
Benign7
Conflicting9
35
Pathogenic
8
Likely Pathogenic
330
VUS
293
Likely Benign
7
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
1
21
0
35
Likely Pathogenic
6
2
0
0
8
VUS
16
257
50
7
330
Likely Benign
0
0
139
154
293
Benign
0
0
6
1
7
Conflicting
—9
Total35260216162682

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ABCC9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ABCC9-related intellectual disability, myopathy and white matter abnormalities

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gained

ABCC9-related dilated cardiomyopathy

limited
ADUndeterminedUncertain
Cardiac
G2P ↗

ABCC9-related Cantu Syndrome

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkinSkeletalCardiac
G2P ↗
missense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Atrial fibrillation, familial, 12

MIM #614050

Molecular basis of disorder known

Autosomal dominant

Cardiomyopathy, dilated, 1O

MIM #608569

Molecular basis of disorder known

Autosomal dominant

Hypertrichotic osteochondrodysplasia (Cantu syndrome)

MIM #239850

Molecular basis of disorder known

Autosomal dominant

Intellectual disability and myopathy syndrome

MIM #619719

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ABCC9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report.
Nelson PT et al.·Brain
2019
Determining the Likelihood of Disease Pathogenicity Among Incidentally Identified Genetic Variants in Rare Dilated Cardiomyopathy-Associated Genes.
Yang Q et al.·J Am Heart Assoc
2022
Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.
Efthymiou S et al.·Brain
2024
Genomic landscape of TCRαβ and TCRγδ T-large granular lymphocyte leukemia.
Cheon H et al.·Blood
2022
Clinical-Genetic Approach to Conditions with Macrocephaly and ASD/Behaviour Abnormalities: Variants in PTEN and PPP2R5D Are the Most Recurrent Gene Mutations in a Patient-Oriented Diagnostic Strategy.
L'Erario FF et al.·Genes (Basel)
2025
Three-dimensional facial morphology in Cantú syndrome.
Roessler HI et al.·Am J Med Genet A
2020
[Clinical characteristics and genetic analysis of a child with Cantú syndrome due to variant of ABCC9 gene].
Xiao M et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2024Case report
ATP-binding cassette transporters in the heart.
Solbach TF et al.·Trends Cardiovasc Med
2006Review
Generalized hypertrichosis syndromes in Mexico.
Aguayo-Orozco TA et al.·Am J Med Genet C Semin Med Genet
2020
Novel human ABCC9/SUR2 brain-expressed transcripts and an eQTL relevant to hippocampal sclerosis of aging.
Nelson PT et al.·J Neurochem
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools