ABCG8 R543S - GET-Evidence



(ABCG8 Arg543Ser)

Short summary

This variant is predicted to cause sitosterolemia (inability to break down plant sterols) in a recessive manner, although this finding lacked statistical significance. Sitosterolemia may be underdiagnosed as it has symptoms similar to hypercholesterolemia and hyperlipidemia.

Variant evidence
Computational 3

Other variants in this gene cause the disease, Polyphen 2 predicts damaging effect

Functional -

p = 0.18

See Lu K et al. 2001 (11452359).

Familial -
Clinical importance
Severity 3


Treatability 4

dietary elimination of plant sterols, cholesterol absorption inhibitor

Penetrance 5

Presumed high penetrance



High clinical importance, Uncertain pathogenic

(The "high 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 @ chr2:44102425: 0.0% (2/10758) in EVS
  • T @ chr2:43955928: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.0% (2/10758)


Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H, Ose L, Stalenhoef AF, Mietinnen T, Bjorkhem I, Bruckert E, Pandya A, Brewer HB Jr, Salen G, Dean M, Srivastava A, Patel SB. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet. 2001 Aug;69(2):278-90. Epub 2001 Jul 9. PubMed PMID: 11452359; PubMed Central PMCID: PMC1201544.

This paper implicates mutations in ABCG5 and ABCG8 as causing sitosterolemia. Out of 37 families, one US family case is reported to be compound heterozygous for this variant and a nonsense mutation (Gln172X). All families were found to have mutations in either ABCG5 or ABCG8, strong evidence for both genes is presented.

The evidence for this particular variant is weak. The variant was not seen in controls, which included 69 US individuals and 95 Finnish individuals. Assuming these caucasian controls can be combined, this is case+: 1, case-: 36, case+: 0, case-: 164. This gives p=0.18 with two-tailed fisher’s exact test.


hu0D879F - CGI sample GS00253-DNA_G01_200_37
het T @ chr2:44102425


Other external references

  • Score: 1.0 (probably damaging)

Other in silico analyses

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 4

Edit history

Gene search

"GENE" or "GENE A123C":

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