ELAC2 S217L - GET-Evidence


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(ELAC2 Ser217Leu)

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Short summary

Reported to be associated with increased susceptibility to prostate cancer, but later studies weaken the hypothesis. Xu et al.‘s meta-analysis concludes that there is a small but significant increased risk (OR = 1.13). Assuming a lifetime risk of 16% for prostate cancer we calculate this leads to an increased risk of ~1.5% (17.5% total).

Variant evidence
Computational 1

Other variants in this gene are associated with prostate cancer, disruptive amino acid change, but Polyphen 2 predicts it to be benign

Functional -
Case/Control 3

See Xu B et al. 2010 (20231859).


No familial evidence.

Clinical importance
Severity 3

There is a low risk of mortality caused by prostate cancer, even if untreated

Treatability 3
Penetrance 2

~1.5% attributable increased risk

See Xu B et al. 2010 (20231859), unpublished research (below).



Low clinical importance, Uncertain pathogenic

(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

Case/control numbers are used from cases referenced by Xu et al. (where they note that they only use numbers from the most recent publication when multiple publications used the same data source). Case+ and case- are counting the instances of the variant allele vs. reference allele in cases.

Using PGP calculator and an estimated lifetime risk of prostate cancer of 16%, this variant has ~1.5% attributable increased risk (17.5% total).

Total cases/controls case+ case– control+ control– p-value odds ratio
Prostate cancer
178 1116 242 1262 0.0894 0.832


Allele frequency

  • A @ chr17:12915009: 27.3% (2942/10758) in EVS
  • A @ chr17:12855733: 24.6% (31/126) in GET-Evidence
  • Frequency shown in summary reports: 27.3% (2942/10758)


Shea PR, Ferrell RE, Patrick AL, Kuller LH, Bunker CH. ELAC2 and prostate cancer risk in Afro-Caribbeans of Tobago. Hum Genet. 2002 Oct;111(4-5):398-400. Epub 2002 Aug 21. PubMed PMID: 12384782.

In a study of Afro-Caribbean males from Tobago, S217L and A514T polymorphisms were genotyped in cases and controls. (A514T was homozygous for reference/low-risk allele in all cases and controls.) For S217L the case/control numbers are: case S/S: 71, case S/L: 43, case L/L: 5. Control S/S: 130, control S/L: 82, Control L/L: 11.

Cases/controls case+ case– control+ control– p-value odds ratio
Prostate cancer
53 185 104 342 0.7755 0.942


Yokomizo A, Koga H, Kinukawa N, Tsukamoto T, Hirao Y, Akaza H, Mori M, Naito S. HPC2/ELAC2 polymorphism associated with Japanese sporadic prostate cancer. Prostate. 2004 Nov 1;61(3):248-52. PubMed PMID: 15368467.

A screen of 285 sporadic prostate cancer cases in Japanese patients and 233 matched controls for S217L and A541T. case S/S: 271, S/L: 14, L/L: 0. Control S/S: 224, S/L: 9, L/L: 0.

Cases/controls case+ case– control+ control– p-value odds ratio
Prostate cancer
14 556 9 457 0.6736 1.279


Robbins CM, Hernandez W, Ahaghotu C, Bennett J, Hoke G, Mason T, Pettaway CA, Vijayakumar S, Weinrich S, Furbert-Harris P, Dunston G, Powell IJ, Carpten JD, Kittles RA. Association of HPC2/ELAC2 and RNASEL non-synonymous variants with prostate cancer risk in African American familial and sporadic cases. Prostate. 2008 Dec 1;68(16):1790-7. PubMed PMID: 18767027.

A study in African American families found little correlation between S217L and prostate cancer (they note a p=0.03 difference in heterozygote sporadic cases). Sporadic cases: L/L: 3, S/L: 69, S/S: 83. Familial cases: L/L: 3, S/L: 30, S/S: 55. Controls: L/L: 15, S/L: 99, S/S: 182. Combined numbers, counting alleles is used below.

Cases/controls case+ case– control+ control– p-value odds ratio
Prostate cancer
111 375 129 463 0.7131 1.062


Xu B, Tong N, Li JM, Zhang ZD, Wu HF. ELAC2 polymorphisms and prostate cancer risk: a meta-analysis based on 18 case-control studies. Prostate Cancer Prostatic Dis. 2010 Mar 16. [Epub ahead of print] PubMed PMID: 20231859.

The most recent meta-analysis of ELAC2 polymorphisms Ser217Leu and Ala541Thr, this concludes that these are associated with prostate cancer and may be “low-penetrance susceptibility markers of prostate cancer”. They note that there is publication bias for results supporting pathogenicity (p = 0.006) but that no single paper is necessary for their conclusion of pathogenicity (ie removal of any single paper doesn’t change this result).

The meta-analysis combines data from many studies and their combine OR is 1.13 with a 95% confidence interval of 1.03 to 1.24.


hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het A @ chr17:12915009


hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr17:12915009


hu9385BA - CGI sample GS00253-DNA_E01_200_37
het A @ chr17:12915009


huC30901 - CGI sample GS00253-DNA_B01_200_37
het A @ chr17:12915009


Added in this revision:

GS06985 - var-GS06985-1100-36-ASM
het A @ chr17:12855734


GS06994 - var-GS06994-1100-36-ASM
het A @ chr17:12855734


GS07357 - var-GS07357-1100-36-ASM
het A @ chr17:12855734


GS10851 - var-GS10851-1100-36-ASM
het A @ chr17:12855734


GS18502 - var-GS18502-1100-36-ASM
het A @ chr17:12855734
















Other external references

  • rs4792311
  • Score: 0.025 (benign)
    Web search results (50 hits -- see all)
  • ELAC2 and prostate cancer risk in Afro-Caribbeans of Tobago.
    ELAC2 and prostate cancer risk in Afro-Caribbeans of Tobago. ... The frequency of the high-risk Leu allele at the S217L site was the same in cases and controls. ...
  • Mendelian Inheritance in Man Document Reader
    ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent ... reported missense changes, S217L and A541T, were identified ...
  • ELAC2 (elaC homolog 2 (E. coli))
    ELAC2 (elaC homolog 2 (E. coli)), Authors: Yang Chen, Sean Tavtigian, Donna Shattuck. Published in: Atlas Genet Cytogenet Oncol Haematol.
  • Table 1
    dietary fats; may account for 20% of. Alzheimer disease. Age-related ... ELAC2. S217L. Prostate cancer. 0.30 and 0.04. Increased risk. Odds ratio 2.4-3.1. and A541T ...
  • AceView: Gene:ELAC2, a comprehensive annotation of human ...
    AceView offers a comprehensive annotation of human, mouse and nematode genes reconstructed by co-alignment and clustering of all publicly available mRNAs and ESTs on ...
  • Characterization of TRZ1 , a yeast homolog of the human ...
    In humans, mutation of ELAC2 is associated with an increased risk of prostate cancer. ... ELAC2 (S217L) No. ELAC2 (A541T) No. ELAC2 (R781H) No. ELAC2 (1641insG) No. ELAC1. No. TRZ1 WT ...
  • Selected article
    Science, global weekly of science ... S217L. A541T. Japanese. 350 sporadic. 242 control. prostate cancer risk. 95. A541T. Japanese. 285 sporadic. 233 control. OR 4.02 (1.50, 10.8) ...
  • Polymorphisms in the Prostate Cancer Susceptibility Gene HPC2 ...
    ... HPC2/ELAC2 that throws translation out of frame after amino acid 547 and that ... The S217L variation was detected as follows: 37 ng of genomic DNA was amplified ...

Other in silico analyses

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 3

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Gene search

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