RNASEL R462Q - GET-Evidence



(RNASEL Arg462Gln)

Short summary

Associated with increased risk of prostate cancer in individuals who already have a family history of prostate cancer, but studies have been unable to replicate this finding in sporadic (non-familial) prostate cancer cases.

Variant evidence
Computational 1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 2

p=0.011 reported in a family-based study (using siblings as controls), but population-level studies are unable to reproduce the result. p = 0.07 for familial cases in Rokman et al, p = 0.03 for familial cases in Wang et al.

See 11941539, Wang L et al. 2002 (12022038), 12415269, Daugherty SE et al. 2007 (17407163).


No LOD scores reported

See 12415269.

Clinical importance
Severity 4
Treatability 4
Penetrance 2

May increase risk, up to twofold, in individuals with a family history of prostate cancer.



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


Allele frequency

  • T @ chr1:182554557: 27.8% (2991/10758) in EVS
  • T @ chr1:180821179: 21.1% (27/128) in GET-Evidence
  • Frequency shown in summary reports: 27.8% (2991/10758)


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PubMed PMID: 11941539

In a study of 116 families with hereditary prostate cancer (HPC), in 492 patients with unselected prostate cancer (PRCA), and in 566 controls, this variant had no significantly higher concentration in PRCA cases (14.4%) vs. controls (13.1%). Concentration in HPC cases was more significant but still very weak (p = 0.07, 22.7% allele frequency).

Wang L, McDonnell SK, Elkins DA, Slager SL, Christensen E, Marks AF, Cunningham JM, Peterson BJ, Jacobsen SJ, Cerhan JR, Blute ML, Schaid DJ, Thibodeau SN. Analysis of the RNASEL gene in familial and sporadic prostate cancer. Am J Hum Genet. 2002 Jul;71(1):116-23. Epub 2002 May 17. Erratum in: Am J Hum Genet 2002 Aug;71(2):449. PubMed PMID: 12022038; PubMed Central PMCID: PMC384968.

In familial cases the variant is again associated with prostate cancer risk (p = 0.03), especially for earlier onset cases (< 64 years). However, association was not found for sporadic cases — this variant seems to be associated with risk in familial cases only.

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PubMed PMID: 12415269

The authors report investigating RNASEL variants in a kindred with prostate cancer and report not seeing any “clearly inactivating mutations” but report two variants, Arg462Gln and Asp541Glu, seen with some suggestive allele frequencies of 35% and 59%. Investigating impact on function, they found that R462Q had three times lower enzyme activity.

To investigate further, they conducted a family-based case/control study with 423 cases and 454 sibling controls. They found a p = 0.011 significance for higher frequency of the variant in cases vs. controls, suggesting 50% increased risk of prostate cancer in heterozygotes and twofold risk in homozygotes.

Daugherty SE, Hayes RB, Yeager M, Andriole GL, Chatterjee N, Huang WY, Isaacs WB, Platz EA. RNASEL Arg462Gln polymorphism and prostate cancer in PLCO. Prostate. 2007 Jun 1;67(8):849-54. PubMed PMID: 17407163.

Comparison of 1,317 prostate cancer cases and 1,842 controls was made. Among the combined group of non-hispanic whites & blacks, cases: Arg/Arg: 536, Gln/Arg: 528, Gln/Gln: 150, and controls: Arg/Arg: 831, Gln/Arg: 700, Gln/Gln: 193.

The most dramatic difference would be expected to be between the homozygotes, based on the hypothesis made by Casey et al., but no statistically significant difference can be seen. The authors note that this is consistent with other attempts to replicate the findings of Casey et al.: “Several other studies, including a population-based study conducted in Sweden, have not found an association between the Arg462Gln polymorphism and sporadic prostate cancer [11,14,16]. The strongest evidence for an association …. has been among hereditary prostate cancer cases …. even these associations are somewhat inconsistent [11,13,14].”


hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het T @ chr1:182554557


hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr1:182554557


hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het T @ chr1:182554557



hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
hom T @ chr1:182554557


hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het T @ chr1:182554557



hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het T @ chr1:182554557


hu43860C - CGI sample GS00253-DNA_A01_200_37
het T @ chr1:182554557


hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het T @ chr1:182554557


hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
hom T @ chr1:182554557


hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het T @ chr1:182554557


hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
het T @ chr1:182554557


hu9385BA - CGI sample GS00253-DNA_E01_200_37
het T @ chr1:182554557


huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het T @ chr1:182554557



huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het T @ chr1:182554557


huAE6220 - CGI sample GS00253-DNA_H01_200_37
hom T @ chr1:182554557


huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr1:182554557


huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het T @ chr1:182554557


huC30901 - CGI sample GS00253-DNA_B01_200_37
het T @ chr1:182554557


huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
hom T @ chr1:182554557


huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het T @ chr1:182554557


huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
het T @ chr1:182554557


huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het T @ chr1:182554557


GS06985 - var-GS06985-1100-36-ASM
het T @ chr1:180821180


GS06994 - var-GS06994-1100-36-ASM
hom T @ chr1:180821180


GS07357 - var-GS07357-1100-36-ASM
het T @ chr1:180821180


GS18537 - var-GS18537-1100-36-ASM
het T @ chr1:180821180


GS18558 - var-GS18558-1100-36-ASM
het T @ chr1:180821180


GS18956 - var-GS18956-1100-36-ASM
het T @ chr1:180821180


GS19649 - var-GS19649-1100-36-ASM
het T @ chr1:180821180


GS19703 - var-GS19703-1100-36-ASM
het T @ chr1:180821180


GS20502 - var-GS20502-1100-36-ASM
het T @ chr1:180821180


GS20509 - var-GS20509-1100-36-ASM
het T @ chr1:180821180


Other external references

  • rs486907
  • Score: 0.964 (probably damaging)
    Web search results (978 hits -- see all)
  • Life Extension Daily News
    Life Extension Daily News ... increased risk of advanced prostate cancer: modification by RNASEL R462Q variant. Carcinogenesis, 2007;28(6):1232-6) ...
  • Prostate Cancer - Research reports on prostate cancer from ...
    NewsRx is the leading source of news and information on Prostate Cancer ... increased risk of advanced prostate cancer: modification by RNASEL R462Q variant. ...
  • Trans Fatty Acid Intake and Increased Risk of Advanced ...
    Trans Fatty Acid Intake and Increased Risk of Advanced Prostate Cancer: Modification by RNASEL R462Q Variant ... cancer may be modified by the functional RNASEL variant R462Q. ...
  • Identification of a Novel Gammaretrovirus in Prostate Tumors ...
    zygous R462Q; QR, RNASEL heterozygous R462Q; RNase L, Ribonuclease L; RR, ... role of RNASEL, the authors sought to examine if a virus might be ...
  • Involvement of the RNAse L gene in prostate cancer
    The RNASEL gene codes for a 80 kDa endoribonuclease, RNAse L, composed ... Analysis of the RNAseL R462Q polymorphism in patients. with sporadic prostate cancer in ...
  • trans-Fatty acid intake and increased risk of advanced ...
    RNASEL R462Q and advanced prostate cancer using unconditional logistic ... RNASEL R462Q modiļ¬es the effect of trans-fatty acids on prostate cancer ...
  • Identification of a Novel Gammaretrovirus in Prostate Tumors ...
    Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant ... prostate cancer risk in patients with the R462Q RNASEL variant. ...
  • Effects of RNase L Mutations Associated with Prostate Cancer ...
    In contrast, the R462Q variant, previously implicated in up to 13% of ... For example, we recently implicated the R462Q variant of RNASEL (1385GA) in unselected (including both ...
  • Free Association: RNase L revisited
    Adding to concerns over RNASEL as a prostate cancer susceptibility gene was the nature of its function. ... to show conclusively that the RNASEL R462Q variant is a risk factor ...
  • Genetic mutation can double prostate cancer risk in some men
    ... a mutation of the RNASEL gene known as R462Q, making R462Q one of the most ... that the R462Q variant cripples the normal function of RNASEL, but does not stop ...

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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