ABCC6 R1268Q - GET-Evidence


ABCC6 R1268Q

(ABCC6 Arg1268Gln)

Short summary

This common polymorphism appears to not have a significant phenotypic impact. A few studies report weak but significant associations with plasma lipids (in Inuits) and thalidomide toxicity.

Variant evidence
Computational -1

Not a disruptive amino acid change according to BLOSUM100, Polyphen predicts this is benign.

Functional -
Case/Control 3

Some report weak but statistically significant associations to lipids or drug interactions.

See 10913334, Wang J et al. 2001 (11776382), 20038957.


No familial data

Clinical importance
Severity 1
Penetrance 1


Low clinical importance, Uncertain pharmacogenetic

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • T @ chr16:16251599: 21.9% (2355/10758) in EVS
  • T @ chr16:16159099: 13.3% (17/128) in GET-Evidence
  • Frequency shown in summary reports: 21.9% (2355/10758)


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PubMed PMID: 10811882

This variant is described as being compound heterozygous in three of eight families with PXE.

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PubMed PMID: 10913334

The authors report noticing this variant in a large Pseudoxanthoma elasticum (PXE) pedigree and, upon following up, finding in an unrelated partner and at a relatively high frequency in their Caucasian controls (62 subjects). Three healthy volunteers were homozygous for this variant. They conclude that the variant does not cause PXE although it could have a modifier role.

Wang J, Near S, Young K, Connelly PW, Hegele RA. ABCC6 gene polymorphism associated with variation in plasma lipoproteins. J Hum Genet. 2001;46(12):699-705. PubMed PMID: 11776382.

In a study of 216 Inuit, the authors report that this variant is associated with lower plasma triglycerides and higher plasma HDL cholesterol (p = 0.012 and p = 0.045, respectively). They magnitude of the effect is not reported, and the authors do not report on how much of overall variance this variant would explain.

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PubMed PMID: 20038957

This variant has a weak but statistically significant association with toxicity of thalidomide, but it’s unclear from the publication whether carriers of the variant are more or less susceptible.


hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het T @ chr16:16251599



hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het T @ chr16:16251599


hu2DBF2D - CGI sample GS01173-DNA_G02 from PGP sample 67180598
het T @ chr16:16251599



hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het T @ chr16:16251599


hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
het T @ chr16:16251599


hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het T @ chr16:16251599


hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het T @ chr16:16251599


hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het T @ chr16:16251599


hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het T @ chr16:16251599




huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het T @ chr16:16251599


huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr16:16251599


huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het T @ chr16:16251599


huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het T @ chr16:16251599


huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
het T @ chr16:16251599


GS07357 - var-GS07357-1100-36-ASM
hom T @ chr16:16159100


GS10851 - var-GS10851-1100-36-ASM
het T @ chr16:16159100


GS12004 - var-GS12004-1100-36-ASM
hom T @ chr16:16159100


GS18502 - var-GS18502-1100-36-ASM
het T @ chr16:16159100


GS19239 - var-GS19239-1100-36-ASM
het T @ chr16:16159100


GS19669 - var-GS19669-1100-36-ASM
hom T @ chr16:16159100


GS19701 - var-GS19701-1100-36-ASM
het T @ chr16:16159100


GS20509 - var-GS20509-1100-36-ASM
het T @ chr16:16159100


Other external references

  • rs2238472
  • [Prostatic Neoplasms]
    [docetaxel; thalidomide]
    Risk or phenotype-associated allele: G Phenotype: The ABCC6 rs2238472 G variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.006 Type of association: CO; TOX
    Web search results (93 hits -- see all)
  • Template Paper
    In this study we investigated the association of the ABCC6 gene and AS. ... In conclusion, the missense mutation R1268Q in the ABCC6 gene is not a specific marker of PXE, but is ...
  • Four most Frequent PXE Mutations in the ABCC6 Gene are not ...
    Background: Mutations in ABCC6 cause Pseudoxanthoma elasticum (PXE), a mendelian disorder ... Q378X) and two SNP (V614A, R1268Q) in a total of 3316 participants ...
  • Directory of open access journals
    In this study we investigated the association of the ABCC6 gene and AS. ... In conclusion, the missense mutation R1268Q in the ABCC6 gene is not a specific marker of PXE, but is ...
  • Retina International's Scientific Newsletter - ABCC6 Mutations
    R1268Q, single heterozygote (1) PXE. Arg 1141 ter. C-T. 3421. 24. BsiYI ... Base-Pair Substitutions in the ABCC6 Gene Results in Pseudoxanthoma Elasticum. ...
  • Pharma DMET - SNPedia
    Gene Symbol Marker Name Translation Table Name Category Marker Type ... snp rs6416668 ABCC6 ABCC6_53629C>T(P945P) noncore snp rs2856585 ABCC6 ABCC6_65693G>A(R1268Q) noncore snp ...
  • ABCC6 Gene - GeneCards | MRP6 Protein | MRP6 Antibody
    Complete information for ABCC6 gene (protein-coding), ATP-binding cassette, sub-family C (CFTR/MRP), member 6
  • A Spectrum of ABCC6 Mutations Is Responsible for ...
    A Spectrum of ABCC6 Mutations Is Responsible for Pseudoxanthoma Elasticum ... X (2000) Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum ...
  • Mendelian Inheritance in Man Document Reader
    The ABCC6 protein consists of 1,503 amino acids with a molecular weight of 165 ... high expression of ABCC6 in liver and kidney, ABCC6 substrates may be ...

Other in silico analyses

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 4

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Gene search

"GENE" or "GENE A123C":

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