• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
RET (HGNC:9967) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
ret proto-oncogene
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
HSCR1, MEN2A, MTC1, MEN2B
Alias symbols
PTC, CDHF12, RET51, CDHR16
%HI
1.58(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.12(Read more about gnomAD LOEUF score)
Cytoband
10q11.21
Genomic Coordinates
GRCh37/hg19: chr10:43572517-43625799 NCBI Ensembl UCSC
GRCh38/hg38: chr10:43077069-43130351 NCBI Ensembl UCSC
MANE Select Transcript
NM_020975.6 ENST00000355710.8 (Read more about MANE Select)
Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis du... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-13234
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
08/26/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 11694544
    Amiel & Lyonnet 2001 wrote "Hirschsprung disease, associated syndromes, and genetics: a review" describing over 80 variants in RET (including large deletions encompassing the enire gene, microdeletions and insertions, nonsense, missense and splicing mutations identified in individuals with Hirschsprung disease (PMIDs 7633441, 8654369 and 9090527). The authors described haploinsufficiency as the most likely disease mechanism.
  • PUBMED: 11953745
    Gabriel et al. 2002 described four probands with RET nonsense or frameshift mutations, and three families harbored sequence alterations that could affect normal RET splicing. They also showed that other probands and families had other heterozygous RET mutations or RET-dependent loci described as RET expression modifiers.
  • PUBMED: 30970187
    Tilghman et al. 2019 genotyped and exome-sequenced samples from 190 patients with Hirschsprung's disease to quantify the genetic burden in patients with this condition. At least one identifiable genetic risk factor was found in 72.1% of the patients, and at least 48.4% of patients had a heterozygous structural or regulatory deficiency in the gene encoding RET gene. According to the authors, this finding highlights the fact that reduced RET expression is the predominant cause of Hirschsprung’s disease.
HI Evidence Comments:
Deletions and loss of function mutations are associated with both familial and sporadic Hirschsprung disease. A complete review is available online in Gene Reviews and PMIDs 11694544, 15617541, and 17965226. IMPORTANT: Deletions and loss of function mutations are NOT associated with MEN (Multiple endocrine neoplasia) type 2A, 2B, and Familial Medullary Thyroid Cancer. According to GeneReviews, these other health conditions are associated with RET gain-of-function mutations: (https://www.ncbi.nlm.nih.gov/books/NBK1257/).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000010.10) (NC_000010.11)