ABCC6

Chr 16ARAD

ATP binding cassette subfamily C member 6

Also known as: ABC34, ARA, EST349056, GACI2, MLP1, MOAT-E, MOATE, MRP6

The ABCC6 protein is an ATP-dependent transporter that actively extrudes physiological compounds and xenobiotics from cells, including glutathione conjugates and other organic compounds. Mutations cause pseudoxanthoma elasticum (a connective tissue disorder affecting skin, eyes, and cardiovascular system) and generalized arterial calcification of infancy, both involving abnormal calcium deposition in elastic tissues. Inheritance is typically autosomal recessive, though autosomal dominant forms also occur.

OMIMResearchSummary from OMIM, UniProt
LOFmechanismAR/ADLOEUF 1.033 OMIM phenotypes
Clinical SummaryABCC6
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Gene-Disease Validity (ClinGen)
inherited pseudoxanthoma elasticum · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.36
OE 0.83 (0.671.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.09Z-score
OE missense 1.11 (1.051.17)
926 obs / 837.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.83 (0.671.03)
00.351.4
Missense OE1.11 (1.051.17)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 60 / 72.5Missense obs/exp: 926 / 837.4Syn Z: -1.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveABCC6-related pseudoxanthoma elasticumLOFAR
definitiveABCC6-related arterial calcification, generalized, of infancyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7228th %ile
GOF
0.73top 25%
LOF
0.2871th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFHu et al. (2003) suggested that the PXE phenotype of the R1141X mutation most likely results from complete loss of function or functional haploinsufficiency of ABCC6.PMID:12714611

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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