RET |
- 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:
- Hirschsprung disease Monarch
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)