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Aliases for RET Gene

Aliases for RET Gene

  • Ret Proto-Oncogene 2 3 5
  • Cadherin-Related Family Member 16 2 3
  • Rearranged During Transfection 2 3
  • RET Receptor Tyrosine Kinase 2 3
  • Cadherin Family Member 12 3 4
  • Proto-Oncogene C-Ret 3 4
  • EC 2.7.10.1 4 56
  • CDHF12 3 4
  • CDHR16 3 4
  • PTC 3 4
  • Ret Proto-Oncogene (Multiple Endocrine Neoplasia And Medullary Thyroid Carcinoma 1, Hirschsprung Disease) 3
  • Multiple Endocrine Neoplasia And Medullary Thyroid Carcinoma 1 2
  • Proto-Oncogene Tyrosine-Protein Kinase Receptor Ret 3
  • Hirschsprung Disease 1 2
  • EC 2.7.10 56
  • RET-ELE1 3
  • HSCR1 3
  • MEN2A 3
  • MEN2B 3
  • RET51 4
  • MTC1 3

External Ids for RET Gene

Previous HGNC Symbols for RET Gene

  • HSCR1
  • MEN2A
  • MTC1
  • MEN2B

Previous GeneCards Identifiers for RET Gene

  • GC10P042861
  • GC10P043347
  • GC10P042856
  • GC10P042892
  • GC10P043572
  • GC10P040098

Summaries for RET Gene

Entrez Gene Summary for RET Gene

  • This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]

CIViC summary for RET Gene

  • RET mutations and the RET fusion RET-PTC lead to activation of this tyrosine kinase receptor and are associated with thyroid cancers. RET point mutations are the most common mutations identified in medullary thyroid cancer (MTC) with germline and somatic mutations in RET associated with hereditary and sporadic forms, respectively. The most common somatic form mutation is M918T (exon 16) and a variety of other mutations effecting exons 10, 11 and 15 have been described. The prognostic significance of these mutations have been hotly debated in the field, however, data suggests that some RET mutation may confer drug resistence. No RET-specific agents are currently clinically available but several promiscuous kinase inhibitors that target RET, among others, have been approved for MTC treatment.

GeneCards Summary for RET Gene

RET (Ret Proto-Oncogene) is a Protein Coding gene. Diseases associated with RET include Thyroid Carcinoma, Familial Medullary and Multiple Endocrine Neoplasia, Type Iia. Among its related pathways are RET signaling and Cytokine Signaling in Immune system. Gene Ontology (GO) annotations related to this gene include calcium ion binding and protein kinase activity. An important paralog of this gene is KDR.

UniProtKB/Swiss-Prot for RET Gene

  • 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 during embryonic life, and promotes the formation of Peyers patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.

Tocris Summary for RET Gene

Gene Wiki entry for RET Gene

Additional gene information for RET Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RET Gene

Genomics for RET Gene

GeneHancer (GH) Regulatory Elements for RET Gene

Promoters and enhancers for RET Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10I043076 Promoter 1.5 EPDnew Ensembl 550.8 +0.2 174 0.8 KLF1 MAZ SIN3A ZIC2 RFX5 E2F1 CTBP1 GLIS2 HDAC2 MTA1 RET CSGALNACT2 PIR60596
GH10I043077 Enhancer 0.6 ENCODE 550.8 -0.5 -489 0.1 CTCF ZIC2 E2F1 CTBP1 GLIS2 HDAC2 ZNF341 ZBTB26 ZBTB17 EZH2 RET CSGALNACT2 GC10M043057
GH10I043104 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE 12.8 +28.3 28341 1.6 ARID4B SIN3A ZNF2 GLIS2 ZNF213 ARID2 ZNF207 ZNF143 KLF7 ATF7 CSGALNACT2 RET RASGEF1A PIR60596 GC10M043121
GH10I042951 Enhancer 1.3 VISTA Ensembl ENCODE 7.4 -124.7 -124737 1.8 CTCF KLF1 MAX SIN3A ZIC2 EGR1 EZH2 MAZ MNT NR2F2 RET ENSG00000259869 LINC00839 ZNF33B LINC01264 GC10M042909
GH10I042932 Enhancer 0.8 Ensembl ENCODE 11.5 -143.3 -143286 2.3 NFIB ETV1 CEBPB INSM2 CEBPG ZIC2 ZFHX2 POLR2A ZNF629 CREB1 RET CSGALNACT2 LOC441666 ENSG00000259869 ZNF33B GC10M042909 LINC01264
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around RET on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RET gene promoter:

Genomic Locations for RET Gene

Genomic Locations for RET Gene
chr10:43,077,027-43,130,351
(GRCh38/hg38)
Size:
53,325 bases
Orientation:
Plus strand
chr10:43,572,475-43,625,799
(GRCh37/hg19)

Genomic View for RET Gene

Genes around RET on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RET Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RET Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RET Gene

Proteins for RET Gene

  • Protein details for RET Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P07949-RET_HUMAN
    Recommended name:
    Proto-oncogene tyrosine-protein kinase receptor Ret
    Protein Accession:
    P07949
    Secondary Accessions:
    • A8K6Z2
    • Q15250
    • Q9BTB0
    • Q9H4A2

    Protein attributes for RET Gene

    Size:
    1114 amino acids
    Molecular mass:
    124319 Da
    Quaternary structure:
    • Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5. The phosphorylated form interacts with PLCG1 and GRB7. Interacts (not phosphorylated) with PTK2/FAK1 (via FERM domain). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas. Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex. Binds to ARTN. Interacts (inactive) with CBLC and CD2AP; dissociates upon activation by GDNF which increases CBLC:CD2AP interaction.
    Miscellaneous:
    • Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC).
    SequenceCaution:
    • Sequence=AAA36524.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=AAA36786.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=CAA33787.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=CAC14882.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RET Gene

    Alternative splice isoforms for RET Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RET Gene

Selected DME Specific Peptides for RET Gene

P07949:
  • RDLAARN
  • VAVKMLK
  • WMAIESL

Post-translational modifications for RET Gene

  • Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. Dephosphorylated by PTPRJ on Tyr-905, Tyr-1015 and Tyr-1062.
  • Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell-membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons.
  • Glycosylation at isoforms=298, isoforms=2151, isoforms=2199, Asn336, Asn343, isoforms=2361, Asn367, Asn377, Asn394, Asn448, isoforms=2468, and Asn554

Domains & Families for RET Gene

Gene Families for RET Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Graphical View of Domain Structure for InterPro Entry

P07949

UniProtKB/Swiss-Prot:

RET_HUMAN :
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
genes like me logo Genes that share domains with RET: view

Function for RET Gene

Molecular function for RET Gene

GENATLAS Biochemistry:
glial cell line derived neurotrophic factor (GDNF) receptor component,homodimerizing and binding the GDNF-GFRA complex,expressed in the developing kidney,the presumptive enteric neuroblats,cranial ganglia (VII,VIII,IX and X) and in the presumptive motor neurons of the spinal cord,interacting with SHC1 transduction adaptor protein,potentially involved in peripheral nerve repair
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Repressed by 4-(3-hydroxyanilino)-quinolines derivatives, indolin-2-one-derivatives, 2-(alkylsulfanyl)-4-(3-thienyl) nicotinonitrile analogs, 3- and 4-substituted beta-carbolin-1-ones, vandetanib, motesanib, sorafenib (BAY 43-9006), cabozantinib (XL184), sunitinib, and withaferin A (WA). Inactivation by sorafenib both reduces kinase activity and promotes lysosomal degradation.
UniProtKB/Swiss-Prot 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 during embryonic life, and promotes the formation of Peyers patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.
UniProtKB/Swiss-Prot Induction:
Positively regulated by NKX2-1, PHOX2B, SOX10 and PAX3.

Enzyme Numbers (IUBMB) for RET Gene

Phenotypes From GWAS Catalog for RET Gene

Gene Ontology (GO) - Molecular Function for RET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA --
GO:0004713 protein tyrosine kinase activity TAS 7824936
GO:0004714 transmembrane receptor protein tyrosine kinase activity TAS --
GO:0004872 receptor activity TAS 7824936
genes like me logo Genes that share ontologies with RET: view
genes like me logo Genes that share phenotypes with RET: view

Human Phenotype Ontology for RET Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RET Gene

MGI Knock Outs for RET:

Clone Products

  • Addgene plasmids for RET

No data available for Transcription Factor Targets and HOMER Transcription for RET Gene

Localization for RET Gene

Subcellular locations from UniProtKB/Swiss-Prot for RET Gene

Cell membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RET gene
Compartment Confidence
plasma membrane 5
cytosol 5
endosome 5
extracellular 3
cytoskeleton 2
nucleus 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Plasma membrane (3)
  • Vesicles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
GO:0005829 cytosol IDA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 19823924
genes like me logo Genes that share ontologies with RET: view

Pathways & Interactions for RET Gene

SuperPathway Contained pathways
1 RET signaling
2 Developmental Biology
3 Cytokine Signaling in Immune system
4 Innate Immune System
5 Signaling by GPCR
genes like me logo Genes that share pathways with RET: view

SIGNOR curated interactions for RET Gene

Activates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for RET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0001657 ureteric bud development IEA --
GO:0001755 neural crest cell migration IEA --
GO:0001838 embryonic epithelial tube formation IEA --
GO:0006468 protein phosphorylation TAS 7824936
genes like me logo Genes that share ontologies with RET: view

Drugs & Compounds for RET Gene

(74) Drugs for RET Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, FDA Approved Drugs, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Vandetanib Approved April 2011 Pharma Target, inhibitor, Biomarker VEGFR, EGFR, and RET inhibitor, EGFR Inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
cabozantinib Approved, Investigational Pharma Target, antagonist, inhibitor Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
regorafenib Approved Pharma Target, inhibitor Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
imatinib Approved Pharma Target, inhibitor Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors 0
Sorafenib Approved, Investigational Pharma Target, inhibitor, inhibitors Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 717

(20) Additional Compounds for RET Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0

(12) ApexBio Compounds for RET Gene

Compound Action Cas Number
Amuvatinib (MP-470, HPK 56) Tyrosine kinase inhibitor 850879-09-3
Apatinib VEGFR2 inhibitor, orally bioavailable, selective 811803-05-1
AST 487 RET kinase inhibitor 630124-46-8
Cabozantinib (XL184, BMS-907351) VEGFR2/Met/Ret/Kit/FLT//AXL inhibitor 849217-68-1
Danusertib (PHA-739358) Pan-aurora kinase inhibitor 827318-97-8
Motesanib Diphosphate (AMG-706) VEGFR/ PDGFR/c-Kit/Ret inhibitor 857876-30-3
Regorafenib Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1 755037-03-7
Regorafenib hydrochloride 835621-07-3
Regorafenib monohydrate Tyrosine kinase inhibitor 1019206-88-2
SU5416 VEGF receptor inhibitor and AHR agonist 204005-46-9
Sunitinib malate VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor 341031-54-7
TG101209 JAK2/3 inhibitor 936091-14-4
genes like me logo Genes that share compounds with RET: view

Drug Products

Transcripts for RET Gene

Unigene Clusters for RET Gene

Ret proto-oncogene:
Representative Sequences:

Clone Products

  • Addgene plasmids for RET

Alternative Splicing Database (ASD) splice patterns (SP) for RET Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20
SP1: -
SP2:
SP3: - - - - - - - - -
SP4: - - - - - - - -

Relevant External Links for RET Gene

GeneLoc Exon Structure for
RET
ECgene alternative splicing isoforms for
RET

Expression for RET Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RET Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RET Gene

This gene is overexpressed in Brain - Substantia nigra (x7.2).

Protein differential expression in normal tissues from HIPED for RET Gene

This gene is overexpressed in Cervix (61.5) and Peripheral blood mononuclear cells (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for RET Gene



Protein tissue co-expression partners for RET Gene

NURSA nuclear receptor signaling pathways regulating expression of RET Gene:

RET

SOURCE GeneReport for Unigene cluster for RET Gene:

Hs.350321

Evidence on tissue expression from TISSUES for RET Gene

  • Nervous system(4.8)
  • Blood(4.4)
  • Thyroid gland(3.7)
  • Adrenal gland(2.9)
  • Intestine(2.4)
  • Lymph node(2.3)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RET Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • larynx
  • lip
  • mandible
  • maxilla
  • meninges
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • parathyroid
  • pituitary gland
  • skull
  • thyroid
  • tongue
  • vocal cord
Thorax:
  • breast
  • chest wall
  • clavicle
  • diaphragm
  • esophagus
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
  • trachea
Abdomen:
  • adrenal gland
  • duodenum
  • intestine
  • kidney
  • large intestine
  • pancreas
  • small intestine
  • stomach
Pelvis:
  • ovary
  • pelvis
  • placenta
  • rectum
  • ureter
  • urethra
  • urinary bladder
  • uterus
  • vagina
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • sweat gland
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with RET: view

No data available for mRNA Expression by UniProt/SwissProt for RET Gene

Orthologs for RET Gene

This gene was present in the common ancestor of animals.

Orthologs for RET Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RET 33 34
  • 96.18 (n)
cow
(Bos Taurus)
Mammalia RET 33 34
  • 87.04 (n)
dog
(Canis familiaris)
Mammalia RET 33 34
  • 86.4 (n)
rat
(Rattus norvegicus)
Mammalia Ret 33
  • 83.33 (n)
mouse
(Mus musculus)
Mammalia Ret 33 16 34
  • 82.78 (n)
oppossum
(Monodelphis domestica)
Mammalia RET 34
  • 74 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RET 34
  • 59 (a)
OneToOne
chicken
(Gallus gallus)
Aves RET 33 34
  • 66.44 (n)
lizard
(Anolis carolinensis)
Reptilia RET 34
  • 60 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ret 33
  • 64.3 (n)
African clawed frog
(Xenopus laevis)
Amphibia ret-A 33
zebrafish
(Danio rerio)
Actinopterygii ret 33 34
  • 63.74 (n)
ret1 33
fruit fly
(Drosophila melanogaster)
Insecta tor 35
  • 49 (a)
Ret 35 34
  • 40 (a)
worm
(Caenorhabditis elegans)
Secernentea R151.4 35
  • 39 (a)
C24G6.2a 35
  • 37 (a)
C24G6.2b 35
  • 37 (a)
kin-9 35
  • 36 (a)
F09A5.2 35
  • 33 (a)
kin-16 35
  • 33 (a)
ver-4 35
  • 33 (a)
Y50D4B.6 35
  • 33 (a)
Y38H6C.20 35
  • 31 (a)
F59A3.8 35
  • 30 (a)
W01B6.5 35
  • 30 (a)
R09D1.12 35
  • 29 (a)
F09G2.1 35
  • 27 (a)
Species where no ortholog for RET was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RET Gene

ENSEMBL:
Gene Tree for RET (if available)
TreeFam:
Gene Tree for RET (if available)

Paralogs for RET Gene

genes like me logo Genes that share paralogs with RET: view

Variants for RET Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for RET Gene

RET_HUMAN-P07949
The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease.

Sequence variations from dbSNP and Humsavar for RET Gene

SNP ID Clin Chr 10 pos Variation AA Info Type
rs1006106202 uncertain-significance, Pheochromocytoma, Renal adysplasia, Multiple endocrine neoplasia, Hirschsprung Disease, Dominant 43,102,600(+) A/G coding_sequence_variant, missense_variant
rs1010091281 uncertain-significance, Multiple endocrine neoplasia, type 2, not specified 43,120,127(+) G/A coding_sequence_variant, missense_variant
rs1011350432 uncertain-significance, Multiple endocrine neoplasia, Pheochromocytoma, Renal adysplasia, Hirschsprung Disease, Dominant 43,077,127(+) G/T 5_prime_UTR_variant
rs1014122393 uncertain-significance, Multiple endocrine neoplasia, type 2 43,126,712(+) C/A/G/T coding_sequence_variant, missense_variant, synonymous_variant
rs1031388542 uncertain-significance, Multiple endocrine neoplasia, type 2 43,113,610(+) G/T coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for RET Gene

Variant ID Type Subtype PubMed ID
nsv951564 CNV deletion 24416366
nsv825350 CNV gain 20364138
nsv550695 CNV gain 21841781
nsv522592 CNV loss 19592680
nsv522566 CNV loss 19592680
nsv1161940 CNV duplication 26073780
nsv1143500 CNV deletion 24896259
nsv1052276 CNV gain 25217958
nsv1042310 CNV loss 25217958
nsv1038102 CNV gain 25217958
esv275022 CNV gain+loss 21479260
dgv727n100 CNV gain 25217958
dgv726n100 CNV gain 25217958
dgv725n100 CNV gain 25217958
dgv724n100 CNV gain 25217958
dgv723n100 CNV gain 25217958

Variation tolerance for RET Gene

Residual Variation Intolerance Score: 11.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.47; 77.48% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RET Gene

Human Gene Mutation Database (HGMD)
RET
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RET

Disorders for RET Gene

MalaCards: The human disease database

(81) MalaCards diseases for RET Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
thyroid carcinoma, familial medullary
  • mtc
multiple endocrine neoplasia, type iia
  • men2a
multiple endocrine neoplasia, type iib
  • men2b
hirschsprung disease 1
  • hirschsprung disease, susceptibility to, 1
pheochromocytoma
  • pheochromocytoma, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search RET in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RET_HUMAN
  • Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The disease may be caused by mutations affecting the gene represented in this entry.
  • Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269 PubMed:12086152, ECO:0000269 PubMed:14566559, ECO:0000269 PubMed:9497256}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Hirschsprung disease 1 (HSCR1) [MIM:142623]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. {ECO:0000269 PubMed:10090908, ECO:0000269 PubMed:10484767, ECO:0000269 PubMed:10618407, ECO:0000269 PubMed:22174939, ECO:0000269 PubMed:7581377, ECO:0000269 PubMed:7633441, ECO:0000269 PubMed:7704557, ECO:0000269 PubMed:7881414, ECO:0000269 PubMed:8114938, ECO:0000269 PubMed:8114939, ECO:0000269 PubMed:9043870, ECO:0000269 PubMed:9090527, ECO:0000269 PubMed:9094028, ECO:0000269 PubMed:9259198, ECO:0000269 PubMed:9384613, ECO:0000269 Ref.56}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Medullary thyroid carcinoma (MTC) [MIM:155240]: Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation. {ECO:0000269 PubMed:10323403, ECO:0000269 PubMed:10826520, ECO:0000269 PubMed:11692159, ECO:0000269 PubMed:7784092, ECO:0000269 PubMed:7845675, ECO:0000269 PubMed:7849720, ECO:0000269 PubMed:7874109, ECO:0000269 PubMed:7881414, ECO:0000269 PubMed:7915165, ECO:0000269 PubMed:8103403, ECO:0000269 PubMed:8557249, ECO:0000269 PubMed:8625130, ECO:0000269 PubMed:8807338, ECO:0000269 PubMed:9223675, ECO:0000269 PubMed:9259198, ECO:0000269 PubMed:9398735, ECO:0000269 PubMed:9452077, ECO:0000269 PubMed:9506724, ECO:0000269 PubMed:9621513, ECO:0000269 PubMed:9677065}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Multiple neoplasia 2A (MEN2A) [MIM:171400]: The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism. {ECO:0000269 PubMed:10522989, ECO:0000269 PubMed:7860065, ECO:0000269 PubMed:7874109, ECO:0000269 PubMed:7881414, ECO:0000269 PubMed:7915165, ECO:0000269 PubMed:8099202, ECO:0000269 PubMed:8103403, ECO:0000269 PubMed:8626834, ECO:0000269 PubMed:8807338, ECO:0000269 PubMed:9097963, ECO:0000269 PubMed:9384613, ECO:0000269 PubMed:9452064}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Multiple neoplasia 2B (MEN2B) [MIM:162300]: Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases. {ECO:0000269 PubMed:7906417, ECO:0000269 PubMed:7906866, ECO:0000269 PubMed:7911697, ECO:0000269 PubMed:8595427, ECO:0000269 PubMed:8807338, ECO:0000269 PubMed:9294615, ECO:0000269 PubMed:9360560}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=Mutations in RET have been detected in patients with renal agenesis suggesting a possible involvement of this gene in disease pathogenesis.
  • Note=Various chromosomal aberrations involving RET are known. Some of them have been found in papillary thyroid carcinomas (PTCs) (PubMed:12787916, PubMed:2406025, PubMed:10980597, PubMed:10439047). Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene (PubMed:2406025). Inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene. Translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene (PubMed:2734021). Translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion (PubMed:10980597). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the Delta RFP/RET oncogene (PubMed:12787916). Translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene (PubMed:10439047). Translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene (PubMed:10439047). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the TRIM27/RET oncogene (PubMed:3037315). {ECO:0000269 PubMed:10439047, ECO:0000269 PubMed:10980597, ECO:0000269 PubMed:12787916, ECO:0000269 PubMed:2406025, ECO:0000269 PubMed:2734021, ECO:0000269 PubMed:3037315}.
  • Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269 PubMed:12000816}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for RET

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Tumor Gene Database
(TGDB)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with RET: view

No data available for Genatlas for RET Gene

Publications for RET Gene

  1. Germ-line mutations in nonsyndromic pheochromocytoma. (PMID: 12000816) Neumann HP … Freiburg-Warsaw-Columbus Pheochromocytoma Study Group (The New England journal of medicine 2002) 3 4 22 44 58
  2. Reduced RET expression in gut tissue of individuals carrying risk alleles of Hirschsprung's disease. (PMID: 20089534) Miao X … Garcia-Barceló M (Human molecular genetics 2010) 3 22 44 58