Gene
ret
- ID
- ZDB-GENE-980526-307
- Name
- ret proto-oncogene receptor tyrosine kinase
- Symbol
- ret Nomenclature History
- Previous Names
- Type
- protein_coding_gene
- Location
- Chr: 13 Mapping Details/Browsers
- Description
- 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).
- Genome Resources
- Note
- None
- Comparative Information
-
- All Expression Data
- 43 figures from 32 publications
- Cross-Species Comparison
- High Throughput Data
- Thisse Expression Data
- No data available
Wild Type Expression Summary
- All Phenotype Data
- 26 figures from 15 publications
- Cross-Species Comparison
- Alliance
Phenotype Summary
Mutations
| Allele | Type | Localization | Consequence | Mutagen | Supplier |
|---|---|---|---|---|---|
| hu2846 | Allele with one point mutation | Unknown | Premature Stop | ENU | |
| ihb309 | Allele with one deletion | Exon 4 | Unknown | CRISPR | |
| ihb310 | Allele with one delins | Exon 4 | Unknown | CRISPR | |
| la018487Tg | Transgenic insertion | Unknown | Unknown | DNA | |
| sa2684 | Allele with one point mutation | Unknown | Premature Stop | ENU | |
| sa15240 | Allele with one point mutation | Unknown | Premature Stop | ENU | |
| sa22307 | Allele with one point mutation | Unknown | Premature Stop | ENU | |
| sa35492 | Allele with one point mutation | Unknown | Splice Site | ENU | |
| sa42210 | Allele with one point mutation | Unknown | Premature Stop | ENU | |
| wmr1 | Allele with one deletion | Exon 8 | Unknown | CRISPR |
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| Targeting Reagent | Created Alleles | Citations |
|---|---|---|
| CRISPR1-ret | Lopez-Rivera et al., 2017 | |
| CRISPR2-ret | (3) | |
| CRISPR3-ret | (2) | |
| CRISPR4-ret | Moreno-Campos et al., 2024 | |
| MO1-ret | N/A | (2) |
| MO2-ret | N/A | (7) |
| MO3-ret | N/A | (3) |
| MO4-ret | N/A | Heanue et al., 2008 |
| MO5-ret | N/A | (2) |
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Human Disease
| Disease Ontology Term | Multi-Species Data | OMIM Term | OMIM Phenotype ID |
|---|---|---|---|
| familial medullary thyroid carcinoma | Alliance | Medullary thyroid carcinoma | 155240 |
| multiple endocrine neoplasia type 2A | Alliance | Multiple endocrine neoplasia IIA | 171400 |
| multiple endocrine neoplasia type 2B | Alliance | Multiple endocrine neoplasia IIB | 162300 |
| pheochromocytoma | Alliance | Pheochromocytoma | 171300 |
| {Hirschsprung disease, protection against} | 142623 |
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| Human Disease | Fish | Conditions | Citations |
|---|---|---|---|
| Hirschsprung's disease | retwmr1/+; em2Tg/em2Tg | standard conditions | Baker et al., 2022 |
| Hirschsprung's disease | rethu2846/+ | standard conditions | Heanue et al., 2016 |
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Domain, Family, and Site Summary
| Type | InterPro ID | Name |
|---|---|---|
| Active_site | IPR008266 | Tyrosine-protein kinase, active site |
| Binding_site | IPR017441 | Protein kinase, ATP binding site |
| Domain | IPR000719 | Protein kinase domain |
| Domain | IPR001245 | Serine-threonine/tyrosine-protein kinase, catalytic domain |
| Domain | IPR002126 | Cadherin-like |
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Domain Details Per Protein
| Protein | Additional Resources | Length | Cadherin-like | Cadherin-like superfamily | Protein kinase, ATP binding site | Protein kinase domain | Protein kinase-like domain superfamily | Receptor Tyrosine Kinase | Ret, cadherin like domain 1 | RET, cadherin-like domain 4 | RET, cysteine rich domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | Tyrosine-protein kinase, active site | Tyrosine-protein kinase, catalytic domain | Tyrosine-protein kinase receptor Ret, cadherin like domain 3 | Tyrosine-protein kinase, Ret receptor |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| UniProtKB:A8E7C6 | InterPro PDB | 1106 |
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Interactions and Pathways
No data available
| Name | Type | Antigen Genes | Isotype | Host Organism | Assay | Source | Citations |
|---|---|---|---|---|---|---|---|
| Ab1-ret | polyclonal | Rabbit |
|
Santa Cruz Biotechnology, Inc.
|
4 |
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Plasmids
No data available
| Construct | Regulatory Region | Coding Sequence | Species | Tg Lines | Citations |
|---|---|---|---|---|---|
| TgBAC(ret:EGFP) |
|
| 1 | Bandla et al., 2022 | |
| Tg(ret1:GFP) |
|
| 1 | (5) |
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| Relationship | Marker Type | Marker | Accession Numbers | Citations |
|---|---|---|---|---|
| Contained in | BAC | DKEY-192P21 | ZFIN Curated Data | |
| Encodes | EST | fd13h01 |
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| Type | Accession # | Sequence | Length (nt/aa) | Analysis |
|---|---|---|---|---|
| RNA | RefSeq:NM_131365 (1) | 4145 nt | ||
| Genomic | GenBank:AC124155 (1) | 173037 nt | ||
| Polypeptide | UniProtKB:A8E7C6 (1) | 1106 aa |
- Moreno-Campos, R., Singleton, E.W., Uribe, R.A. (2024) A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system. PLoS One. 19:e0303914e0303914
- Ren, M., Chen, X., Dai, L., Tu, J., Hu, H., Sun, X., Luo, J., Li, P., Fu, Y., Zhu, Y., Sun, W., Tang, Z., Liu, M., Ren, X., Lu, Q. (2024) Knockout of dhx38 Causes Inner Ear Developmental Defects in Zebrafish. Biomedicines. 13:
- Chi, S., Li, S., Cao, G., Guo, J., Han, Y., Zhou, Y., Zhang, X., Li, Y., Luo, Z., Li, X., Rong, L., Zhang, M., Li, L., Tang, S. (2023) The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung's disease. Frontiers in cell and developmental biology. 11:11847991184799
- Kuil, L.E., Chauhan, R.K., de Graaf, B.M., Cheng, W.W., Kakiailatu, N.J.M., Lasabuda, R., Verhaeghe, C., Windster, J.D., Schriemer, D., Azmani, Z., Brooks, A.S., Edie, S., Reeves, R.H., Eggen, B.J.L., Shepherd, I.T., Burns, A.J., Hofstra, R.M.W., Melotte, V., Brosens, E., Alves, M.M. (2023) ATP5PO levels regulate enteric nervous system development in zebrafish, linking Hirschsprung disease to Down Syndrome. Biochimica et biophysica acta. Molecular basis of disease. 1870(3):166991
- Baker, P.A., Ibarra-García-Padilla, R., Venkatesh, A., Singleton, E.W., Uribe, R.A. (2022) In Toto imaging of early enteric nervous system Development reveals that gut colonization is tied to proliferation downstream of ret. Development (Cambridge, England). 149(21)
- Bandla, A., Melancon, E., Taylor, C.R., Davidson, A.E., Eisen, J.S., Ganz, J. (2022) A New Transgenic Tool to Study the Ret Signaling Pathway in the Enteric Nervous System. International Journal of Molecular Sciences. 23(24):
- Feng, G., Sun, Y. (2022) The Polycomb group gene rnf2 is essential for central and enteric neural system development in zebrafish. Frontiers in neuroscience. 16:960149
- Xiao, J., Meng, X., Chen, K., Wang, J., Wu, L., Chen, Y., Yu, X., Feng, J., Li, Z. (2022) Down-Regulation of Double C2 Domain Alpha Promotes the Formation of Hyperplastic Nerve Fibers in Aganglionic Segments of Hirschsprung's Disease. International Journal of Molecular Sciences. 23(18)
- Adams, S.E., Purkiss, A.G., Knowles, P.P., Nans, A., Briggs, D.C., Borg, A., Earl, C.P., Goodman, K.M., Nawrotek, A., Borg, A.J., McIntosh, P.B., Houghton, F.M., Kjær, S., McDonald, N.Q. (2021) A two-site flexible clamp mechanism for RET-GDNF-GFRα1 assembly reveals both conformational adaptation and strict geometric spacing. Structure (London, England : 1993). 29(7):694-708.e7
- Kuil, L.E., MacKenzie, K.C., Tang, C.S., Windster, J.D., Le, T.L., Karim, A., de Graaf, B.M., van der Helm, R., van Bever, Y., Sloots, C.E.J., Meeussen, C., Tibboel, D., de Klein, A., Wijnen, R.M.H., Amiel, J., Lyonnet, S., Garcia-Barcelo, M.M., Tam, P.K.H., Alves, M.M., Brooks, A.S., Hofstra, R.M.W., Brosens, E. (2021) Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development. PLoS Genetics. 17:e1009698
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