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RET Gene

protein-coding GIFtS: 73

GC10P040098

ret proto-oncogene
(Previous names: multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease 1 )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database
(Previous symbols: HSCR1, MEN2A, MTC1, MEN2B)

		Products

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase)
About This Section

Aliases & Descriptions
ret proto-oncogene¹ ²		cadherin-related family member 16²
CDHF12¹ ² ³		proto-oncogene tyrosine-protein kinase receptor Ret²
RET51¹ ²		RET transforming sequence²
CDHR16¹ ²		RET-ELE1²
PTC¹ ²		hydroxyaryl-protein kinase²
Cadherin family member 12² ³		HSCR1²
Proto-oncogene c-Ret² ³		receptor tyrosine kinase²
MEN2A² ⁵		OTTHUMP00000216967²
Hirschsprung disease 1¹		MEN2B²
multiple endocrine neoplasia and medullary thyroid carcinoma 1¹		MTC1²
ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease)²		EC 2.7.10.1³

External Ids:	HGNC: 9967¹	Entrez Gene: 5979²	Ensembl: ENSG00000165731⁷	UniProtKB: P07949³

Export aliases for RET gene to outside databases

Previous GC identifers: GC10P042861 GC10P043040 GC10P043347 GC10P042856 GC10P042892 GC10P043572

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for RET:

This gene, a member of the cadherin superfamily, encodes one of the receptor tyrosine kinases, which are cell-surface

molecules that transduce signals for cell growth and differentiation. This gene plays a crucial role in neural crest

development, and it can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement. Mutations in

this gene are associated with the disorders multiple endocrine neoplasia, type IIA, multiple endocrine neoplasia, type

IIB, Hirschsprung disease, and medullary thyroid carcinoma. Two transcript variants encoding different isoforms have

been found for this gene. Additional transcript variants have been described but their biological validity has not

been confirmed. (provided by RefSeq)

UniProtKB/Swiss-Prot: RET_HUMAN, P07949

Function: Probable receptor with tyrosine-protein kinase activity; important for development

Gene Wiki entry for RET (RET proto-oncogene)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 60), Regulatory elements and Epigenetics data according to Qiagen and/or SABiosciences)
About This Section

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the RET gene promoter:
         NF-kappaB1   AP-1   STAT5A   c-Jun   c-Fos   HSF1 (long)   Elk-1   STAT5B   NF-kappaB   STAT3
         Other transcription factors

Search SABiosciences Chromatin IP Primers for RET

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays for RET

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 10q11.2 Ensembl cytogenetic band: 10q11.21 HGNC cytogenetic band: 10q11.2

RET Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RET gene location

GeneLoc gene densities for chromosome 10 GeneLoc Exon Structure

GeneLoc location for GC10P040098: view genomic region (about GC identifiers)

Start:	40,098,756 bp from pter
End:	40,151,896 bp from pter
Size:	53,141 bases
Orientation:	plus strand

1 alternative location:

Chr10+ 43,572,475-43,625,799

RefSeq DNA sequence:

NC_000010.10 NT_033985.7

(According to ¹UniProtKB, neXtProt, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Millipore, Sigma-Aldrich, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, and/or ProSpec,
Biochemical Assays by Millipore, Sigma-Aldrich, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Dec 2010 and Entrez Gene, Antibodies by Millipore, Sigma-Aldrich, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, and/or Epitomics)
About This Section

UniProtKB/Swiss-Prot: RET_HUMAN, P07949 (See protein sequence)

Recommended Name: Proto-oncogene tyrosine-protein kinase receptor Ret precursor

Size: 1114 amino acids; 124319 Da

Subunit: Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5 (By similarity)

Subcellular location: Membrane; Single-pass type I membrane protein

Sequence caution: Sequence=AAA36524.1; Type=Erroneous initiation; Sequence=CAA33787.1; Type=Erroneous initiation;

Sequence=CAC14882.1; Type=Erroneous initiation;

PDB structures from and Proteopedia :

1XPD (3D)

2IVS (3D)

2IVT (3D)

2IVU (3D)

2IVV (3D)

2X2K (3D)

2X2L (3D)

2X2M (3D)

2X2U (3D)

Secondary accessions: Q15250 Q9H4A2

Explore the universe of human proteins at neXtProt for RET: NX_P07949

Post-translational modifications:

Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation¹

View phosphorylation sites using PhosphoSite²

REFSEQ proteins (2 alternative transcripts):

NP_065681.1 NP_066124.1

ENSEMBL proteins:

ENSP00000347942 ENSP00000419080 ENSP00000344798

Human Recombinant Proteins

	Millipore Purified and/or Recombinant RET Protein
	Sigma-Aldrich Proteins for RET
	R&D Systems Recombinant & Natural Proteins for RET
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells Browse OriGene Protein Over-expression Lysates
	GenScript Purified and Recombinant Proteins for RET
	Novus Biologicals Proteins for RET
	Novus Biologicals Lysate for RET
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins

2 Gene Ontology (GO) cellular component terms (GO ID links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0016020	membrane	IEA	--
GO:0016021	integral to membrane	IEA	--

About this table

RET for ontologies About GeneDecksing

Antibodies for RET:

	Millipore Mono- and Polyclonal Antibodies for the study of RET
	Sigma-Aldrich Antibodies for RET
	R&D Systems Antibodies for RET
	Cell Signaling Technology (CST) Antibodies for RET
	OriGene Antibodies: RET
	GenScript Superior Antibodies for RET
	Novus Biologicals Antibodies for RET
	Epitomics antibodies for RET

Assays for RET:

	Millipore Kits and Assays for the Analysis of RET
	Browse ELISAs at Sigma-Aldrich
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for RET
	GenScript RET-Activity-based Kinase Assay for Compound Screening
	Cell Signaling Technology (CST) Sandwich ELISA Kits for RET
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for RET

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

RET for domains About GeneDecksing

5/11 InterPro domains/families (see all 11):

IPR017441 Protein_kinase_ATP_BS

IPR020685 Tyr_prot_kinase

IPR015777 Tyr_kinase_Ret_rcpt-like

IPR001245 Ser-Thr/Tyr-Pkinase

IPR002126 Cadherin

Graphical View of Domain Structure for InterPro Entry P07949

ProtoNet protein and cluster: P07949

2 Blocks protein families:

IPB002126 Cadherin

IPB008266 Tyrosine protein kinase

UniProtKB/Swiss-Prot: RET_HUMAN, P07949

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family

Similarity: Contains 1 cadherin domain

Similarity: Contains 1 protein kinase domain

(According to UniProtKB, IUBMB,and/or Genatlas, Animal models from MGI Dec 24 2010,
shRNA from OriGene, Sigma-Aldrich, RNAi from Millipore, siRNAs from Sigma-Aldrich, OriGene, Qiagen, Super-pooled esiRNAs from Sigma-Aldrich, microRNA from Sigma-Aldrich, Qiagen, SABiosciences, Clones from Millipore, Sigma-Aldrich, OriGene, GenScript, Sino Biological, Cell Lines from GenScript, Ontologies according to Gene Ontology Consortium 01 Dec 2010 via Entrez Gene.)
About This Section

UniProtKB/Swiss-Prot: RET_HUMAN, P07949

Function: Probable receptor with tyrosine-protein kinase activity; important for development

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

Enzyme Number (IUBMB): EC 2.7.10.1

Inhib. RNA:		Millipore RNAi Products for the Analysis of RET Gene knock-down
		Sigma-Aldrich Nano Scale siRNA for RET Sigma-Aldrich siRNA Panels and esiRNA and siRNA for RET Sigma-Aldrich shRNA Panels and shRNA for RET
		OriGene 29mer shRNA kits in GFP-retroviral vector (see all 4): RET OriGene shRNA RFP (see all 4): RET OriGene basic RS shRNA (see all 4): RET OriGene siRNA (see all 4): RET
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing of RET

miRNA:		Sigma-Aldrich microRNA Mimics for RET Browse microRNA target validation systems at Sigma-Aldrich
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of RET
		8/12 SABiosciences Assays for microRNAs that regulate RET (see all 12):
		hsa-miR-495 hsa-miR-520d-5p hsa-miR-15a hsa-miR-128 hsa-miR-885-5p hsa-miR-497 hsa-miR-218 hsa-miR-424

Gene
Editing:

Sigma-Aldrich CompoZr Knockout ZFN for RET

Clones:		Browse Clones for the Expression of Recombinant Proteins Available from Millipore
		Browse iPSC Reprogramming Factors at Sigma-Aldrich
		OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): RET OriGene Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): RET OriGene untagged cDNA clones in CMV expression vector (see all 2): RET OriGene 3'-UTR clone (see all 2): RET Browse MicroRNA Expression Plasmids
		GenScript Custom cDNA clone Services for RET
		Browse Sino Biological Human cDNA Clones

Cell
Lines:

GenScript Custom overexpressing Cell Line Services for RET

Genatlas biochemistry entry for RET:

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

5/10 Gene Ontology (GO) molecular function terms (GO ID links to tree view) (see all 10):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000166	nucleotide binding	IEA	--
GO:0004672	protein kinase activity	--	--
GO:0004674	protein serine/threonine kinase activity	--	--
GO:0004713	protein tyrosine kinase activity	TAS	7824936
GO:0004714	transmembrane receptor protein tyrosine kinase activity	IEA	--

About this table

RET for ontologies About GeneDecksing

Animal Models: 15/20 MGI mutant phenotypes (inferred from 40 alleles) (MGI details for Ret) (see all 20):

behavior/neurological	cardiovascular system	cellular	digestive/alimentary	embryogenesis
endocrine/exocrine gland	growth/size	homeostasis/metabolism	lethality-postnatal	lethality-prenatal/perinatal
life span-post-weaning/aging	limbs/digits/tail	muscle	nervous system	no phenotypic analysis

RET for phenotypes About GeneDecksing

(Pathways according to Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB, Sets of similar genes according to GeneDecks, PCR Arrays from SABiosciences, Proteins Network according to SABiosciences, Sigma-Aldrich, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Dec 2010 via Entrez Gene).
About This Section

RET for pathways About GeneDecksing

2 Millipore Pathways for RET

	Development GDNF family signaling
	G-protein signaling H-RAS regulation pathway

1 Sigma-Aldrich "Your Favorite Gene" (powered by Ingenuity) Pathway for RET

Thyroid Cancer Signaling

2 Cell Signaling Technology (CST) Pathways for RET

	Translational Control: Regulation of eIF4E and p70 S6 Kinase
	Protein Acetylation

3 Kegg Pathways (Kegg details for RET):

	hsa04144 Endocytosis
	hsa05200 Pathways in cancer
	hsa05216 Thyroid cancer

SABiosciences Pathway-Focused PCR Array including RET: PAHS-502A

Sigma-Aldrich "Your Favorite Gene" (powered by Ingenuity) Molecular Interaction Network for RET

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for RET

5/40 Interacting proteins for RET (P07949² ENSP00000344798³) via UniProtKB, MINT, and/or STRING (see all 40)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CBL	P22681², ENSP00000264033³	MINT-50071 MINT-60976 MINT-60969 MINT-50072 MINT-60970 MINT-60968 STRING: ENSP00000264033
STAT3	P40763², ENSP00000264657³	MINT-8033149 MINT-8037607 STRING: ENSP00000264657
GRB2	P62993², ENSP00000339007³	MINT-60975 STRING: ENSP00000339007
SHC1	P29353², ENSP00000357432³	MINT-60981 STRING: ENSP00000357432
PLCG1	P19174², ENSP00000362369³	MINT-8034153 STRING: ENSP00000362369

About this table

5/12 Gene Ontology (GO) biological process terms (GO ID links to tree view) (see all 12):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000165	MAPKKK cascade	IEA	--
GO:0001657	ureteric bud development	IEA	--
GO:0001755	neural crest cell migration	IEA	--
GO:0001838	embryonic epithelial tube formation	IEA	--
GO:0006468	protein phosphorylation	IEA	--

About this table

RET for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

RET for compounds About GeneDecksing

Browse Small Molecules at Sigma-Aldrich

Enzo Life Sciences drugs & compounds for RET

Browse Tocris compounds for RET
10/46 Novoseek chemical compound relationships for RET gene (see all 46)

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tyrosine	83.5	488	7678053 (4), 8363602 (4), 11564708 (4), 8114938 (3) (see all 99)
zd6474	77.5	25	19029224 (4), 18245671 (3), 20225331 (2), 15867345 (2) (see all 13)
cysteine	58.5	100	16732321 (3), 20119574 (3), 9097963 (3), 12734540 (2) (see all 67)
succinate	50.8	22	12419172 (1), 17264467 (1), 18334619 (1), 15988378 (1) (see all 17)
sunitinib	48.7	9	19887470 (2), 19453268 (1), 17505827 (1), 19188185 (1) (see all 8)
phosphotyrosine	41.1	7	16847065 (2), 8812115 (1), 10728700 (1), 18756447 (1) (see all 5)
sodium iodide	32.1	1	17391636 (1)
threonine	30.6	10	9075701 (4), 7559902 (1), 11356339 (1), 11351254 (1) (see all 7)
methionine	29.6	6	7559902 (1), 11356339 (1), 11351254 (1), 8884827 (1) (see all 6)
cipa	29.4	4	8957089 (1), 12652644 (1)

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 228 Homo sapiens; Dec 8 2010) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Millipore,
siRNAs from Sigma-Aldrich, OriGene, Qiagen, Super-pooled esiRNAs from Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene, microRNA from Sigma-Aldrich, Qiagen, SABiosciences,
Tagged/untagged cDNA clones from OriGene, Sigma-Aldrich, GenScript, Primers from OriGene and/or SABiosciences)
About This Section

Inhib. RNA:		Millipore RNAi Products for the Analysis of RET Gene knock-down
		Sigma-Aldrich Nano Scale siRNA for RET Sigma-Aldrich siRNA Panels and esiRNA and siRNA for RET Sigma-Aldrich shRNA Panels and shRNA for RET
		OriGene 29mer shRNA kits in GFP-retroviral vector (see all 4): RET OriGene shRNA RFP (see all 4): RET OriGene basic RS shRNA (see all 4): RET OriGene siRNA (see all 4): RET
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing of RET

miRNA:		Sigma-Aldrich microRNA Mimics for RET Browse microRNA target validation systems at Sigma-Aldrich
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of RET
		8/12 SABiosciences Assays for microRNAs that regulate RET (see all 12):
		hsa-miR-495 hsa-miR-520d-5p hsa-miR-15a hsa-miR-128 hsa-miR-885-5p hsa-miR-497 hsa-miR-218 hsa-miR-424

Clones:		Browse FLAG tag genes at Sigma-Aldrich
		OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): RET OriGene Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): RET OriGene untagged cDNA clones in CMV expression vector (see all 2): RET OriGene 3'-UTR Clone (see all 2): RET Browse OriGene MicroRNA Expression Plasmids
		GenScript Custom cDNA clone Services for RET

Primers:		OriGene genome-wide validated SYBR primer pairs: RET Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay for RET: PPH00102A

REFSEQ mRNAs for RET gene (2 alternative transcripts):

NM_020630.4 NM_020975.4

Additional cDNA sequence:

AJ844649.1 AK291807.1 AK294827.1 BC003072.2 BC004257.1 X15262.1 Y12528.1

9 DOTS entries:

DT.40222723 DT.121287046 DT.121287035 DT.95362735 DT.97823574 DT.95362738 DT.100783057 DT.100783060

DT.100807107

24/93 AceView cDNA sequences (see all 93):

BM664772 AI167534 AI204150 AL514642 H24996 NM_020975 NM_020630 AI263439

AA716772 BM703293 BX376397 BX451803 CD630508 CD630504 BQ720918 AL523813

BE261914 BX283168 BF311917 BI195263 CD630494 AW628757 BX501190 AI825524

highest scoring ESTs for RET:

AA983685 BF311917 BF316920 BI195797 BQ279180 BQ720918 CA489570 F07297 X12949 AA716772

Unigene Cluster for RET:

Ret proto-oncogene

Hs.350321 [show with all ESTs]

Unigene Representative Sequence: NM_020975

GeneLoc Exon Structure

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

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:			-		-		-		-		-		-		-		-

About this scheme

ECgene alternative splicing isoforms for RET
4 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000355710(uc001jal.2) ENST00000498820 ENST00000340058(uc001jak.1 uc010qez.1)

ENST00000479913

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 228 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Primers from OriGene and/or SABiosciences )
About This Section

RET expression in normal and diseased human tissues

¹ / ² / ³

11 probe-sets matching RET gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
1823_g_at²^{, 3}	U95-A	1	0.88	1.00	0.90	0.57	HG4677-HT5102	0.20	1.00	0.72	1
1822_at²^{, 3}	U95-A	1	0.69	1.00	0.93	1.00	HG4677-HT5102	0.20	1.00	0.72	1
160028_s_at²^{, 3}	U95-A	1	0.62	1.00	0.86	1.03	X12949	0.80	1.00	0.91	1
91896_at²^{, 3}	U95-D	1	0.50	1.00	0.80	1.73	AA983685	0.80	1.00	0.91	1
1745_at²^{, 3}	U95-A	1	0.44	1.00	0.95	0.87	HG4679-HT5104	0.20	1.00	0.72	1
205879_x_at²^{, 3}	U133-A	1	0.82	1.00	--	--	BC004257	0.60	1.00	0.82	1
215771_x_at²^{, 3}	U133-A	1	0.64	1.00	--	--	X15786	0.40	0.67	0.55	1
211421_s_at²^{, 3}	U133-A	1	0.46	1.00	--	--	M31213	0.20	1.00	0.72	1
205879_x_at²	U133Plus2	1	0.82	1.00	--	--	--	--	--	--	--
215771_x_at²	U133Plus2	1	0.64	1.00	--	--	--	--	--	--	--
211421_s_at²	U133Plus2	1	0.46	1.00	--	--	--	--	--	--	--

About this table

RET for expression About GeneDecksing

Data from Genenote (Publications) and GNF BioGPS
About these images

About these images

CGAP SAGE TAG: --

SOURCE GeneReport for Unigene cluster: Hs.350321

Expression variation in blood from EXPOLDB for RET

Primers:		OriGene genome-wide validated SYBR primer pairs: RET Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay for RET: PPH00102A

SABiosciences Expression via Pathway-Focused PCR Array including RET: PAHS-502A

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Dec 24 2010, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for RET gene from 5/8 species (see all 8)

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	RET¹	--	ret proto-oncogene	87.16(n) 87.96(a)	403494 XM_543915.2 XP_543915.2
rat (Rattus norvegicus)	Ret¹	--	ret proto-oncogene	83.21(n) 84.98(a)	24716 NM_012643.1 NP_036775.1
mouse (Mus musculus)	Ret^{1 , 5}	6 (55.86 cM)⁵	ret proto-oncogene^{1, 5}	82.78(n)¹ 83.47(a)¹	19713¹ NM_009050.2¹ NP_033076.2¹ AF209436⁵ AK044686⁵ (see all 11)
chicken (Gallus gallus)	RET¹	--	ret proto-oncogene	66.13(n) 67.21(a)	396107 NM_205190.1 NP_990521.1
zebrafish (Danio rerio)	ret1²	--	receptor tyrosine kinase	77.47(n)	30512 AF007949.1

About this table Species with no ortholog for RET

ENSEMBL Gene Tree for RET (if available)

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
About This Section

Paralogs for RET gene

FGFR4² TIE1² FGFR1² FGFR2² FGFR3² FLT3² TEK²

RET for paralogs About GeneDecksing

(SNPs according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Resequencing Primers from Qiagen)
About This Section

UniProtKB/Swiss-Prot: RET_HUMAN, P07949

Polymorphism: The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease

SNP ID	Valid	Chr 10 pos	Sequence	Recs	AA Chg	Type	More	Recs	Allele freq	Pop	Total sample	More
Genomic Data				Transcription Related Data				Allele Frequencies
			--	--	--		--	--
rs17028^1,2	C,F,H,	43623812(+)	`TTGGCC/TGAGCC`	1	--	ut3¹		21		EA MN NA NS	2652
rs715106^1,2	C,F,O,A,H,	43616751(+)	`GTGTTA/CCAACC`	2	--	int¹		20		NA EA NS WA	1244
rs741968^1,2	C,F,A,H,	43611708(+)	`TAGTCG/AGAGGT`	2	--	int¹		10		NS NA EA WA	400
rs752975^1,2	C,F,O,A,	43588313(+)	`GCTCTA/GTCCTG`	2	--	int¹		10		NA WA	208
rs752976^1,2	--	43588378(+)	`CCCCGC/TCCCCT`	2	--	int¹		0	--	--	--	--
rs752977^1,2	C,F,A,H,	43588381(+)	`CGTCCC/TCTTAC`	2	--	int¹		13		NS EA NA WA	552
rs752978^1,2	C,F,A,H,	43588429(+)	`GTGCCC/TAGCCC`	2	--	int¹		21		NS EA NA WA	1224
rs760466^1,2	C,	43612226(+)	`CGGGGC/TGGGGG`	2	--	int¹		2		NA	4
rs1799939^1,2	C,F,O,	43610119(+)	`CTTCCG/AGTGCC`	4	/S /G	mis¹ ref¹ ese³		16		EA MN NA NS	2530
rs1800858^1,2	C,F,O,A,	43595968(+)	`CAGGCG/AGCCGG`	4	/A	syn¹ ref¹		12		EU NS EA NA WA	766

About this table

HapMap Linkage Disequilibrium images for RET (up to first 250kb)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for RET: --

QIAGEN SeqTarget long-range PCR primers for resequencing RET

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, LSDB, HGMD, GAD, HuGE Navigator, and/or TGDB.)
About This Section

RET for disorders About GeneDecksing

OMIM: 164761 disorders: 171400 155240 162300 142623 209880 171300 191830

UniProtKB/Swiss-Prot: RET_HUMAN, P07949

Defects in RET may be a cause of colorectal cancer (CRC) [MIM:114500]

Defects in RET are a cause of Hirschsprung disease (HSCR) [MIM:142623]. HSCR is a genetic disorder of neural

crest development characterized by the absence of intramural ganglion cells in the hindgut, often resulting in

intestinal obstruction. Occasionally, MEN2A or FMTC occur in association with HSCR

Defects in RET are the cause of medullary thyroid carcinoma (MTC) [MIM:155240]. MTC is a 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

Defects in RET are the cause of multiple neoplasia type 2B (MEN2B) [MIM:162300]. MEN2B is an uncommon

inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with

marfanoid habitus, mucosal neuromas, skeletal and ophtalmic 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

Defects in RET are a cause of susceptibility to 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

Defects in RET are the cause of multiple neoplasia type 2A (MEN2A) [MIM:171400]; also known as multiple

neoplasia type 2 (MEN2). MEN2A is the most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer

syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism

Defects in RET are a cause of thyroid papillary carcinoma (TPC) [MIM:188550]. TPC is a common tumor of the

thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary

carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of

fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=Chromosomal aberrations

involving RET are found in thyroid papillary carcinomas. Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1)

oncogene; 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; translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET

fusion; translocation t(6;10)(p21.3;q11.2) with RFP generates the Delta RFP/RET oncogene; translocation

t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene; translocation t(7;10)(q32;q11) with TIF1

generates the TIF1/RET (PTC6) oncogene. The PTC5 oncogene has been found in 2 cases of PACT in children exposed to

radioactive fallout after Chernobyl

Defects in RET are a cause of renal adysplasia [MIM:191830]; also known as renal agenesis or renal aplasia.

Renal agenesis refers to the absence of one (unilateral) or both (bilateral) kidneys at birth. Bilateral renal

agenesis belongs to a group of perinatally lethal renal diseases, including severe bilateral renal dysplasia,

unilateral renal agenesis with contralateral dysplasia and severe obstructive uropathy

Defects in RET are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:209880]; also known as

congenital failure of autonomic control or Ondine curse. CCHS is a 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

10/94 Novoseek disease relationships for RET gene (see all 94)

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
men 2a	98.4	707	8849577 (6), 8556060 (6), 9620546 (5), 17573899 (5) (see all 99)
thyroid carcinoma medullary	98	409	7627269 (5), 7864888 (3), 12694233 (3), 16451770 (3) (see all 99)
multiple endocrine neoplasia	98	333	8895732 (2), 9067749 (2), 16343738 (2), 11103773 (2) (see all 99)
thyroid carcinoma, familial medullary	97.6	140	11502806 (3), 14602786 (3), 10323403 (2), 8829625 (2) (see all 99)
hirschsprung disease	95	341	9824583 (6), 17108762 (4), 11955539 (4), 9384613 (4) (see all 99)
men 3	94.5	290	11245446 (8), 9620546 (5), 17573899 (5), 1979053 (4) (see all 99)
thyroid papillary carcinoma	93	251	8626874 (5), 9589668 (4), 17718263 (4), 10337992 (4) (see all 99)
pheochromocytoma	91.3	299	8912182 (7), 14739491 (7), 10953992 (5), 9761126 (5) (see all 99)
germ-line mutation	85.7	62	8895732 (2), 19484261 (2), 9179691 (2), 16419493 (2) (see all 53)
colonic aganglionosis	80.3	9	17640327 (1), 14715928 (1), 7478601 (1), 18081917 (1) (see all 9)

About this table

GeneTests: RET

Hirschsprung Disease

Locus Specific Mutation Databases (LSDB): RET
Human Gene Mutation Database (HGMD): RET
Genetic Association Database (GAD): RET
Human Genome Epidemiology (HuGE) Navigator: RET (128 documents)
Tumor Gene Database (TGDB): RET

Export disorders and mutations for RET gene to outside databases

(Possibly Related Articles in Doctor's Guide)
About This Section

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶UniProtKB/TrEMBL, and/or ⁷Novoseek)
About This Section

10/1483 PubMed articles for RET gene, integrated from 7 sources (see all 1483):
(articles sorted by number of sources associating them with RET)

A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene. (PubMed id 10522989)^{1, 2, 4, 7} Tessitore A.... Colantuoni V. (1999)
Germ-line mutations in nonsyndromic pheochromocytoma. (PubMed id 12000816)^{1, 2, 4, 7} Neumann H.P.H.... Eng C. (2002)
TTF-1 and RET promoter SNPs: regulation of RET transcription in Hirschsprung's disease. (PubMed id 15548547)^{1, 4, 7} Garcia-Barcelo M....Tam P.K. (2005)
Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation. (PubMed id 9384613)^{1, 2, 7} Decker R.A.... Watson P. (1998)
RET exon 11 (G691S) polymorphism is significantly more frequent in sporadic medullary thyroid carcinoma than in the general population. (PubMed id 15240649)^{1, 4, 7} Elisei R....Pinchera A. (2004)
Identification of RET autophosphorylation sites by mass spectrometry. (PubMed id 14711813)^{1, 2, 7} Kawamoto Y.... Nakashima I. (2004)
Two distinct mutations of the RET receptor causing Hirschsprung's disease impair the binding of signalling effectors to a multifunctional docking site. (PubMed id 10484767)^{1, 2, 7} Geneste O.... Billaud M. (1999)
Renal aplasia in humans is associated with RET mutations. (PubMed id 18252215)^{1, 2, 7} Skinner M.A....Freemerman A.J. (2008)
Tyrosines 1015 and 1062 are in vivo autophosphorylation sites in ret and ret-derived oncoproteins. (PubMed id 11061555)^{1, 2, 7} Salvatore D.... Santoro M. (2000)
Mutation analysis of the RET, the endothelin-B receptor, and the endothelin-3 genes in sporadic cases of Hirschsprung's disease. (PubMed id 9094028)^{1, 2, 7} Kusafuka T.... Puri P. (1997)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 5979	HGNC: 9967	AceView: RET	Ensembl:ENSG00000165731	euGenes: HUgn5979
ECgene: RET	Kegg: 5979	H-InvDB: RET

(According to HUGE)
About This Section

(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
ATLAS Chromosomes in Cancer entry for RET	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RET
MEN2 RET database	http://www.arup.utah.edu/database/MEN2/MEN2_welcome.php

Intellectual Property for RET gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from XenneX, Inc.)

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Patent Information for RET gene:
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GeneCards and IP:
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protein-coding GIFtS: 73

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RET (Gene Symbol)
ret proto-oncogene
CDHF12
RET51
CDHR16
PTC
Cadherin family member 12
Proto-oncogene c-Ret
MEN2A
Hirschsprung disease 1
multiple endocrine neoplasia and medullary thyroid carcinoma 1
ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease)
cadherin-related family member 16
proto-oncogene tyrosine-protein kinase receptor Ret
RET transforming sequence
RET-ELE1
hydroxyaryl-protein kinase
HSCR1
receptor tyrosine kinase
OTTHUMP00000216967
MEN2B
MTC1
EC 2.7.10.1

Congenital Disorders
Genetic Susceptibility
von Hippel-Lindau Disease
SHAH-WAARDENBURG SYNDROME
MEN 2a
THYROID CARCINOMA ANAPLASTIC
Obstipation
THYROID FOLLICULAR CARCINOMA
Thyroid Nodule
aggressiveness
PARATHYROID ADENOMA
multiple disorders
PARATHYROID CARCINOMA
Edema
Waardenburgs Syndrome
THYROID CARCINOMA MEDULLARY
Amyloidosis
Cancer
somatic mutations
Endocrine Cancer
motility disorder
polyposis
MEN 3
endocrine neoplasm
Germ-Line Mutation
Thyroid Neoplasms
Hypoparathyroidism
GENITOURINARY ANOMALY
Multiple Endocrine Neoplasia Type 1
Neurofibromatosis Type 1
Tumors
Pheochromocytoma
Metastasis
CENTRAL HYPOVENTILATION SYNDROME, CONGENITAL
molecular pathology
Parathyroid Diseases
Islet Cell Tumor
ENDOCRINE DISORDER
neoplastic transformation
Cushing Syndrome
Developmental Disabilities
Renal dysplasia
glaucoma
Adenoma Follicular
COWDEN DISEASE
parathyroid hyperplasia
Hyperplasia
PITUITARY ADENOMA
HRPT2
Goiter Nodular
Medullary Tumors
Multiple Endocrine Neoplasia
Hirschsprung Disease
Carcinoma
Hyperparathyroidism
Thyroid Cancer
Congenital absence
Allelic Loss
AMYLOIDOSIS, PRIMARY CUTANEOUS
congenital malformation
Carcinoma Papillary
Carcinoid
THYROID PAPILLARY CARCINOMA
Carcinoma Anaplastic
Carcinoma Renal Cell
Pancreatic Cancer
Goiter
Paraganglioma
Neurofibromatosis
Neuroendocrine Tumors
THYROID ADENOMA
Pancreatic tumor
Cancer Syndromes Hereditary
Adenoma
Ganglioneuroma
Total intestinal aganglionosis
Carcinoma Medullary
Enterocolitis
Colonic Aganglionosis
Thyroid Diseases
Renal Agenesis
papillary thyroid cancer
HYPERPARATHYROIDISM PRIMARY
ADRENAL TUMOR
Allelic Imbalance
neoplastic disease
Neuroma
THYROID CARCINOMA, FAMILIAL MEDULLARY
Hashimotos Thyroiditis
genetic disorder
THYROID CARCINOMA
RENAL ANOMALY
Neoplastic Processes
Paraganglioma Extra-Adrenal

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RET Gene

protein-coding GIFtS: 73

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