ClinGen Dosage Sensitivity Curation Page

GREM1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

no evidence for haploinsufficiency

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Although a duplication in exons 3-6 of SCG5 is shown in multiple publications to cause GREM1 increased expression and segregate with colorectal cancer and polyps, as well as interpreted as "Strong" evidence for gene-disease validity in the ClinGen Hereditary Colon Cancer Gene curation group, there is currently no evidence of a whole gene duplication of GREM1 causing a similar phenotype. Based on this, the triplosensitivity of GREM1 is scored as 0. Below are referenced publications on the upstream duplication of exons in SCG5 in relation to GREM1. PMID:26493165 Rohlin et al 2016 describes a family (non-Ashkenazi descent) with a duplication in a gene upstream of GREM1 (SCG5 Exons 3-6), where one carrier was affected with Colorectal Cancer and 6 carriers were affected with colorectal polyps (to such an extent 3 of the 6 received colectomies). PMID:21128281 Venkatachalam et al (2011) describes a 35yo patient with CRC and carrying a duplication in a gene upstream of GREM1 (SCG5 Exons 3-6). The patient has a first degree relative with Colorectal Cancer. PMID:22561515 Jager et al (2012) identifies three families from Ashkenazi or Ashkenazi - descendent lineage, with duplications upstream in SCG5 Exons 3-6 and a history of colorectal adenomas (affected is defined as 3 or more). The initial publication of a large family bearing this same duplication but not as granularly mapped is PMID:12696020 Jaeger et al 2003. The authors include experimental data showing significantly increased expression of GREM1 in normal epithelium and unaffected expression of SCG5.