GFRA1 Gene

Name	GDNF family receptor alpha 1
Description	This gene encodes a member of the glial cell line-derived neurotrophic factor receptor (GDNFR) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature receptor. Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. This receptor is a glycosylphosphatidylinositol (GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for Hirschsprung disease. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The glial cell line‐derived neurotrophic factor (GDNF) family receptor α1 (GFRA1) plays a central role as a specificity‐conferring co‐receptor for GDNF in multiple biological systems. In the testis, GFRA1 is selectively expressed by a subpopulation of spermatogonial stem cells (SSCs) where it partners with the transmembrane receptor RET to mediate GDNF signaling that is essential for SSC self‐renewal, proliferation, and maintenance of an undifferentiated state. This activity is critical for postnatal spermatogenesis and fertility, and GFRA1 expression has even been exploited to isolate and characterize SSCs (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in the germline, GFRA1 is implicated in tumor biology. In triple‐negative breast cancer, for example, a circular RNA derived from the GFRA1 locus (circGFRA1) functions as a competing endogenous RNA by sponging miR‐34a, thereby modulating GFRA1 expression and promoting cancer cell proliferation, survival, and poor clinical outcome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, in osteosarcoma, cisplatin treatment induces GFRA1 expression, which in turn contributes to chemoresistance by regulating autophagy via AMPK‐dependent pathways that operate independently of RET kinase activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the enteric nervous system, GFRA1 works together with RET to transduce GDNF signals that are necessary for proper neuronal circuitry formation and gastrointestinal motility; disruptions in this pathway can impair neuromuscular function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Recent genome‐wide association analyses have also suggested that genetic variants near GFRA1 may contribute to the risk of complex neuropsychiatric traits, such as suicidal behavior in the context of depression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the multifaceted functions of GFRA1—as a key mediator of GDNF signaling, a marker for stem cell populations, and a modulator of cellular responses in cancer and neuronal systems. Its ability to precisely regulate cell fate decisions and survival across diverse tissues highlights GFRA1 as a promising target for therapeutic intervention in reproductive, oncological, and neuropsychiatric disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Cathy K Naughton, Sanjay Jain, Amy M Strickland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.105.047365"}], "href": "https://doi.org/10.1095/biolreprod.105.047365"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16237148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16237148"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marie-Claude Hofmann, Laura Braydich-Stolle, Martin Dym "}, {"type": "b", "children": [{"type": "t", "text": "Isolation of male germ-line stem cells; influence of GDNF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2004.12.006"}], "href": "https://doi.org/10.1016/j.ydbio.2004.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15708562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15708562"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anyanee Buageaw, Meena Sukhwani, Ahmi Ben-Yehudah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GDNF family receptor alpha1 phenotype of spermatogonial stem cells in immature mouse testes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.105.043810"}], "href": "https://doi.org/10.1095/biolreprod.105.043810"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16014811"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16014811"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zuping He, Jiji Jiang, Maria Kokkinaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gdnf upregulates c-Fos transcription via the Ras/Erk1/2 pathway to promote mouse spermatogonial stem cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1634/stemcells.2007-0436"}], "href": "https://doi.org/10.1634/stemcells.2007-0436"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17962702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17962702"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rongfang He, Peng Liu, Xiaoming Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-017-0614-1"}], "href": "https://doi.org/10.1186/s13046-017-0614-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29037220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29037220"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mihwa Kim, Ji-Yeon Jung, Seungho Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2016.1239676"}], "href": "https://doi.org/10.1080/15548627.2016.1239676"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27754745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27754745"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Paola Brun, Maria Cecilia Giron, Marsela Qesari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2013.08.047"}], "href": "https://doi.org/10.1053/j.gastro.2013.08.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23994200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23994200"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Alexandra Schosser, Amy W Butler, Marcus Ising, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomewide association scan of suicidal thoughts and behaviour in major depression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0020690"}], "href": "https://doi.org/10.1371/journal.pone.0020690"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21750702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21750702"}]}]}]}
Synonyms	GDNFRA, RET1L, GDNFR, RETL1, TRNR1, GFR-ALPHA-1
Proteins	GFRA1_HUMAN
NCBI Gene ID	2674
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GFRA1 has 7,705 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for GFRA1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GFRA1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GFRA1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of GFRA1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of GFRA1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of GFRA1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of GFRA1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GFRA1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of GFRA1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GFRA1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GFRA1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of GFRA1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GFRA1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of GFRA1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GFRA1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GFRA1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GFRA1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GFRA1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of GFRA1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GFRA1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GFRA1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GFRA1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing GFRA1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GFRA1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with GFRA1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of GFRA1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GFRA1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GFRA1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GFRA1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GFRA1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GFRA1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with GFRA1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GFRA1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with GFRA1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with GFRA1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GFRA1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GFRA1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GFRA1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GFRA1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing GFRA1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GFRA1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with GFRA1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.