MSR1 R293X - GET-Evidence


MSR1 R293X

(MSR1 Arg293Stop)

Short summary

Associated with increased risk of Barrett’s esophagus and/or esophageal cancer. Our very rough estimate is that the increased risk may be around 4x (25% risk of Barrett’s esophagus, assuming population average is 5%, and 1.2% lifetime risk of esophageal cancer compared to average .4% risk).

Variant evidence
Computational 2

Severe disruptive effect

Functional -
Case/Control 4

See Orloff M et al. 2011 (21791690).

Familial -
Clinical importance
Severity 4

Esophageal cancer

Treatability 3
Penetrance 2

See unpublished research (below).



Low clinical importance, Likely pathogenic

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

Inheritance pattern


Summary of published research, and additional commentary

Orloff et al. report 6.8% of Barrett’s esophagus & esophageal cancer cases carrying this variant, while EVS data has 1.4% of the population as carriers on average. Assuming 5% of the population has Barrett’s, this implies 0.34% (.068 * 5) of the population is both a carrier and has this phenotype — and thus, that 24% of carriers have the phenotype (.34 / 1.4). So carriers are estimated to have ~20% increased risk of Barrett’s esophagus (4x).

If a similar risk effect applies to esophageal cancer, this implies ~1% increased attributable risk of esophageal cancer (assuming about 1 in 250 lifetime risk on average).

Allele frequency

  • A @ chr8:16012594: 0.7% (80/10758) in EVS
  • Frequency shown in summary reports: 0.7% (80/10758)


Xu J, Zheng SL, Komiya A, Mychaleckyj JC, Isaacs SD, Hu JJ, Sterling D, Lange EM, Hawkins GA, Turner A, Ewing CM, Faith DA, Johnson JR, Suzuki H, Bujnovszky P, Wiley KE, DeMarzo AM, Bova GS, Chang B, Hall MC, McCullough DL, Partin AW, Kassabian VS, Carpten JD, Bailey-Wilson JE, Trent JM, Ohar J, Bleecker ER, Walsh PC, Isaacs WB, Meyers DA. Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nat Genet. 2002 Oct;32(2):321-5. Epub 2002 Sep 16. PubMed PMID: 12244320.

In a study of 159 families affected with hereditary prostate cancer, they identified six with this variants in families. They also screen non-hereditary prostate cancer patients and find it in 8 out of 317 cases, and 1 out of 256 controls. They report this as p = 0.047 with Fisher’s Exact text, however notably multiple hypotheses were being tested (eight different variants listed in Table 1).

Wang L, McDonnell SK, Cunningham JM, Hebbring S, Jacobsen SJ, Cerhan JR, Slager SL, Blute ML, Schaid DJ, Thibodeau SN. No association of germline alteration of MSR1 with prostate cancer risk. Nat Genet. 2003 Oct;35(2):128-9. Epub 2003 Sep 7. PubMed PMID: 12958598.

Trying to replicate Xu et al, these authors find no evidence supporting MSR1 mutations being a risk factor for prostate cancer.

Orloff M, Peterson C, He X, Ganapathi S, Heald B, Yang YR, Bebek G, Romigh T, Song JH, Wu W, David S, Cheng Y, Meltzer SJ, Eng C. Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA. 2011 Jul 27;306(4):410-9. PubMed PMID: 21791690.

Eight of 116 patients with Barrett’s esophagus or esophageal adenocarcinoma carried the MSR1-R392X mutation, which was not found in 239 matched controls (p = 0.0001).


Other external references

  • rs41341748

Other in silico analyses

  • NBLOSUM100 score = 10
  • GET-Evidence autoscore = 4

Edit history

Gene search

"GENE" or "GENE A123C":

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