ret ret proto-oncogene receptor tyrosine kinase [Danio rerio (zebrafish)] - Gene

Summary

Official Symbol: retprovided by ZNC
Official Full Name: ret proto-oncogene receptor tyrosine kinaseprovided by ZNC
Primary source: ZFIN:ZDB-GENE-980526-307
See related: Ensembl:ENSDARG00000055305 AllianceGenome:ZFIN:ZDB-GENE-980526-307
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Danio rerio
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; Danionidae; Danioninae; Danio
Also known as: cret; ret1; c-ret; wu:fd13h01; etID315074.13
Summary: Enables protein homodimerization activity. Acts upstream of or within several processes, including autonomic nervous system development; axon extension; and branchiomeric skeletal muscle development. Predicted to be located in endomembrane system and membrane. Predicted to be part of receptor complex. Predicted to be active in axon and plasma membrane. Is expressed in several structures, including embryonic structure; nervous system; pharyngeal arch; pronephros; and vagal neural crest. Used to study Hirschsprung's disease. Human ortholog(s) of this gene implicated in several diseases, including Hirschsprung's disease; familial medullary thyroid carcinoma; multiple endocrine neoplasia type 2A; multiple endocrine neoplasia type 2B; and pheochromocytoma. Orthologous to human RET (ret proto-oncogene). [provided by Alliance of Genome Resources, Jul 2025]
Orthologs: all
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Genomic context

Location:: chromosome: 13

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2025_04	current	GRCz12tu (GCF_049306965.1)	13	NC_133188.1 (28802763..28850939, complement)
RS_2024_08	previous assembly	GRCz11 (GCF_000002035.6)	13	NC_007124.7 (25584660..25632756, complement)

Chromosome 13 - NC_133188.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Sequencing the Zebrafish transcriptome from a range of tissues and developmental stages
Description: Sequencing the Zebrafish transcriptome from a range of tissues and developmental stages
BioProject: PRJEB1986
Analysis date: Fri Dec 8 19:48:10 2017

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A two-site flexible clamp mechanism for RET-GDNF-GFRalpha1 assembly reveals both conformational adaptation and strict geometric spacing.
Title: A two-site flexible clamp mechanism for RET-GDNF-GFRα1 assembly reveals both conformational adaptation and strict geometric spacing.
Authors observed no interaction between efn-A5b and RET from zebrafish, this lack of association indicates how complex efn-A signaling is and suggests that there may be other molecules involved in efn-A5-induced RET signaling.
Title: Binding of EphrinA5 to RET receptor tyrosine kinase: An in vitro study.
These data provide the first evidence for a physiologic role of these isoforms in RET pathway function.
Title: Exon Skipping in the RET Gene Encodes Novel Isoforms That Differentially Regulate RET Protein Signal Transduction.
Significantly, we show that introduction of mapk10 mutations into ret heterozygotes enhanced the ENS deficit, supporting MAPK10 as a Hirschsprung disease (HSCR) susceptibility locus. Our studies demonstrate that ret heterozygous zebrafish is a sensitized model, with many significant advantages over existing murine models, to explore the pathophysiology and complex genetics of HSCR.
Title: A Novel Zebrafish ret Heterozygous Model of Hirschsprung Disease Identifies a Functional Role for mapk10 as a Modifier of Enteric Nervous System Phenotype Severity.
RET expression is investigated within the brain of zebrafish; both RET protein and mRNA are observed.
Title: GDNF family ligand RET receptor in the brain of adult zebrafish.
In animals lacking Ret or Gfra3 function, myogenic gene expression is reduced in forming opercular muscles, but not in non-opercular muscles derived from the same muscle anlagen.
Title: Ret signalling integrates a craniofacial muscle module during development.
genes beyond RET may be implicated in the genesis of sporadic cases of HD
Title: Studies of RET gene expression and acetylcholinesterase activity in a series of sporadic Hirschsprung's disease.
evaluation of noncoding sequences at the zebrafish ret locus conserved among teleosts, and at the human RET locus, conserved among mammals
Title: Conservation of RET regulatory function from human to zebrafish without sequence similarity.

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General gene information

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Markers

fc36a03.y1 (e-PCR)
- UniSTS:193650

fd13h01.x1 (e-PCR)
- UniSTS:204154

ret1 (e-PCR), detects polymorphism
- UniSTS:187026

Gene Ontology Provided by ZFIN

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane receptor protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within branchiomeric skeletal muscle development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within enteric nervous system development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within enteric nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in homophilic cell-cell adhesion	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neural crest cell migration involved in autonomic nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuron projection development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within pronephros morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein-containing complex assembly	IPI Inferred from Physical Interaction more info	PubMed

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of signaling receptor complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: proto-oncogene tyrosine-protein kinase receptor Ret

Names: receptor tyrosine kinase

NP_858048.2

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_181662.2 → NP_858048.2 proto-oncogene tyrosine-protein kinase receptor Ret precursor

Status: PROVISIONAL

Source sequence(s)

JBMGRA010000013

UniProtKB/TrEMBL

A0A8N1Z2F3, A0ACM8QQR2, A8E7C6

Related

ENSDARP00000072093.5, ENSDART00000077627.7

Conserved Domains (3) summary

cd05045
Location:715 → 1004

PTKc_RET; Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein

smart00112
Location:186 → 256

CA; Cadherin repeats

pfam07714
Location:716 → 997

Pkinase_Tyr; Protein tyrosine kinase

RefSeqs of Annotated Genomes: GCF_049306965.1-RS_2025_04

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCz12tu Primary Assembly

Genomic

NC_133188.1 Reference GRCz12tu Primary Assembly

Range

28802763..28850939 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_131365.1: Suppressed sequence

Description

NM_131365.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.