ABCC6

Chr 16ARAD

ATP binding cassette subfamily C member 6

NCBI Gene: 368ENSG00000091262UniProt: O95255

ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of glutathione conjugates such as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS) (in vitro), and an anionic cyclopentapeptide endothelin antagonist, BQ-123 (PubMed:11880368, PubMed:12414644). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Does not appear to actively transport drugs outside the cell. Confers low levels of cellular resistance to etoposide, teniposide, anthracyclines and cisplatin (PubMed:12414644)

Primary Disease Associations & Inheritance

Arterial calcification, generalized, of infancy, 2MIM #614473
AR
Pseudoxanthoma elasticumMIM #264800
AR
Pseudoxanthoma elasticum, forme frusteMIM #177850
AD
2215
ClinVar variants
59
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— ABCC6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 260 VUS of 2215 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.03LOEUF
pLI 0.000
Z-score 1.36
OE 0.83 (0.67–1.03)
Tolerant

Highly tolerant — LoF variants common in population

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.
-1.09Z-score
OE missense 1.11 (1.05–1.17)
926 obs / 837.4 exp
Tolerant

Tolerant to missense variation

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.0.83 (0.67–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.05–1.17)
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.1.07
0≤1.21.6
LoF obs/exp: 60 / 72.5Missense obs/exp: 926 / 837.4Syn Z: -1.09

ClinVar Variant Classifications

2215 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic27
VUS260
Likely Benign130
Benign25
Conflicting9
32
Pathogenic
27
Likely Pathogenic
260
VUS
130
Likely Benign
25
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
2
18
0
32
Likely Pathogenic
13
6
8
0
27
VUS
2
219
30
9
260
Likely Benign
0
4
55
71
130
Benign
0
0
25
0
25
Conflicting
—9
Total2723113680483

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

View in ClinVar →

Protein Context — Lollipop Plot

ABCC6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ABCC6-related pseudoxanthoma elasticum

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

ABCC6-related arterial calcification, generalized, of infancy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Arterial calcification, generalized, of infancy, 2

MIM #614473

Molecular basis of disorder known

Autosomal recessive

Pseudoxanthoma elasticum

MIM #264800

Molecular basis of disorder known

Autosomal recessive

Pseudoxanthoma elasticum, forme fruste

MIM #177850

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic heterogeneity of heritable ectopic mineralization disorders in a large international cohort.
Saeidian AH et al.·Genet Med
2022Cohort
Pseudoxanthoma elasticum - Genetics, pathophysiology, and clinical presentation.
Pfau K et al.·Prog Retin Eye Res
2024Review
Diverse Genetic Landscape of Suspected Retinitis Pigmentosa in a Large Korean Cohort.
Kim YJ et al.·Genes (Basel)
2021Cohort
Reassessment of causality of ABCC6 missense variants associated with pseudoxanthoma elasticum based on Sherloc.
Verschuere S et al.·Genet Med
2021
Pseudoxanthoma elasticum.
Germain DP·Orphanet J Rare Dis
2017Review
The Human Face of ABCC6.
Terry SF·FEBS Lett
2020Review
ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions.
Shimada BK et al.·Int J Mol Sci
2021Review
[Pseudoxanthoma elasticum].
Ladewig MS et al.·Ophthalmologe
2006Review
Generalized Arterial Calcification of Infancy (GACI).
Baujat G et al.·Arch Pediatr
2024Review
Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients.
Park HK et al.·Ann Neurol
2023Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Multi-State Structural Genomics Enables Large-Scale, Mechanistic, and Context-Specific Classification of ABCC6 Genetic Variants Implicated in Calcification Diseases.
Wagenknecht JB et al.·Int J Mol Sci
2026🔓 Open Access
Loss of ABCC6 in Human Mesenchymal Stem Cells Leads to Elevated Reactive Oxygen Species Formation and a Senescence-like Phenotype.
Osterhage MR et al.·Antioxidants (Basel)
2026
ABCC6 Heterozygosity as Genetic Predisposition to Cerebrovascular Disease Across Ages.
Amico G et al.·Genes (Basel)
2026
ABCC6 pathogenic variants are associated with hemorrhagic phenotypes in Japanese patients with severe cerebral small vessel disease.
Kitahara S et al.·Sci Rep
2026🔓 Open AccessCohort
Identification of a Novel Pathogenic ABCC6 Mutation Through Familial Genetic Analysis in Pseudoxanthoma Elasticum: A Case Report.
Liang L et al.·Cureus
2026🔓 Open AccessCase report
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Pseudoxanthoma ElasticumAngioid StreaksPeau d&#39;Orange

Progression Assessment of PXE-associated Alterations

RECRUITING
NCT07048106University Hospital, BonnStarted 2024-09-01
Pseudoxanthoma Elasticum

PPI Supplementation to Fight ECtopIc Calcification in PXE

RECRUITING
NCT04868578Phase NACentre Hospitalier Universitaire de NiceStarted 2022-12-13
study treatment PPIPlacebo comparator
Pseudoxanthoma Elasticum

Purinergic Compounds in Pseudoxanthoma Elasticum

NOT YET RECRUITING
NCT07323082Phase NACentre Hospitalier Universitaire de NiceStarted 2026-01-15
supplementary tubesSCANNER
Gene MutationsPseudoxanthoma ElasticumArterial Calcification

ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency

RECRUITING
NCT06462547Phase PHASE2Inozyme PharmaStarted 2024-06-19
INZ-701

External Resources

Links to major genomics databases and tools