RET protein expression summary - The Human Protein Atlas

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RET

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RET

RET INFORMATION
Proteinⁱ Full gene name according to HGNC.	Ret proto-oncogene
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	RET (CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1, PTC, RET51)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s). Read more	Cancer-related genes Disease related genes Enzymes FDA approved drug targets Human disease related genes Plasma proteins Transporters
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	8
Protein interactions	Interacting with 4 proteins

PROTEIN EXPRESSION AND LOCALIZATION
Tissue profileⁱ A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource. "Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.	Cytoplasmic expression at variable levels in several tissues, mainly in parathyroid gland.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Localized to the Golgi apparatus, Cytosol In addition localized to the Plasma membrane
Brain cellular locationⁱ Manually selected location of the protein positivity, observed by immunofluorescence staining in mouse brain.	Soma and synapse in neurons. Circumventricular organs of ependymal cells.
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.	Membrane, Intracellular (different isoforms)

TISSUE RNA EXPRESSION
Tissue specificityⁱ The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.	Tissue enhanced (Adrenal gland, Parathyroid gland)
Tissue expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Parathyroid gland - Mixed function (mainly)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category	Low human brain regional specificity
Brain expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Monoamines - Neurotransmitter signalling (mainly)

CELL TYPE RNA EXPRESSION
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Cell type enhanced (Adrenal medulla cells, Respiratory ionocytes, Retinal horizontal cells, Breast lactating cells, Fibro-adipogenic progenitors, Corticotrophs, Myosatellite cells)
Single cell type expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Neurons - Neuronal signaling (mainly)
Tissue cell type classificationⁱ Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.	Cell type enriched (Adrenal gland - Adrenal medulla cells, Colon - Colon enteroendocrine cells, Pituitary gland - Corticotropes, Testis - Spermatogonia)
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Not detected in immune cells
Immune cell expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Not detected - no cluster assigned

CANCER & CELL LINES
Prognostic summary	RET is not prognostic
Cancer specificityⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.	Cancer enhanced (Breast Invasive Carcinoma)
Cell line expression clusterⁱ The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Thyroid cancer - Neuronal signaling (mainly)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Group enriched (Neuroblastoma, Thyroid cancer)

PROTEINS IN BLOOD
Upregulated in diseaseⁱ A gene is classified as upregulated in a disease if the average concentration of all samples of that disease is significantly higher (adj P-value<0.005 and NPX difference>=1) than the average concentration of samples of all diseases as measured by PEA . For gender specific diseases the analysis includes only samples corresponding to the same gender from the other diseases.	No
Disease prediction modelⁱ The disease(s) the gene is associated with and able to predict according to glmnet prediction models. To be included the gene has to be upregulated according to differential expression analysis and have more than 50% overall importance as indicated by the prediction models.	Type 2 diabetes (Class,All other diseases), Multiple sclerosis (Class), Coronary artery calcification (All other diseases), E.coli pyelonephritis (Class,All other diseases), MASLD (All other diseases), Metabolic syndrome (Class)
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics dataset obtained from the PeptideAtlas. Read more	Yes
Proximity extension assayⁱ Indicates whether the protein has been measured (Data available) or not (Not available) using the Olink Explore HT proximity extension assay platform. Read more	Data available
SomaScanⁱ Indicates whether the protein has been measured (Data available) or not (Not available) using the SomaScan 11K platform. Read more	Data available

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation 11, 12, 13, 14, 15. GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways 16, 17, 18, 19, 20, 21, 22. Acts as a dependence receptor via the GDNF-GFRA1 signaling: 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 23, 24. Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses 25, 26, 27. 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 28, 29. Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage 30. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors 31. Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 32.... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Cell adhesion
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	ATP-binding, Nucleotide-binding
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	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]... show less

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