GFRAL
GDNF family receptor alpha-like
Also known as: bA360D14.1, C6orf144, GFRAL_HUMAN, GRAL, UNQ9356
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q6UXV0
- Gene
- GFRAL
- Ensembl
- ENSG00000187871
- Chromosome
- 6
- Canonical length
- 394 aa
- Protein class
- Predicted membrane proteins
- Subcellular location
- Nucleoplasm,Plasma membrane,Actin filaments,Focal adhesion sites
OverviewNCBI Gene
Enables glial cell-derived neurotrophic factor receptor activity and receptor tyrosine kinase binding activity. Involved in GDF15-GFRAL signaling pathway; positive regulation of MAPK cascade; and positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction. Located in several cellular components, including actin cytoskeleton; focal adhesion; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]
Canonical amino-acid sequenceUniProt
394 residues, UniProt reviewed canonical sequence.
>Q6UXV0|GFRAL
1 MIVFIFLAMG LSLENEYTSQ TNNCTYLREQ CLRDANGCKH AWRVMEDACN DSDPGDPCKM
61 RNSSYCNLSI QYLVESNFQF KECLCTDDFY CTVNKLLGKK CINKSDNVKE DKFKWNLTTR
121 SHHGFKGMWS CLEVAEACVG DVVCNAQLAS YLKACSANGN PCDLKQCQAA IRFFYQNIPF
181 NIAQMLAFCD CAQSDIPCQQ SKEALHSKTC AVNMVPPPTC LSVIRSCQND ELCRRHYRTF
241 QSKCWQRVTR KCHEDENCIS TLSKQDLTCS GSDDCKAAYI DILGTVLQVQ CTCRTITQSE
301 ESLCKIFQHM LHRKSCFNYP TLSNVKGMAL YTRKHANKIT LTGFHSPFNG EVIYAAMCMT
361 VTCGILLLVM VKLRTSRISS KARDPSSIQI PGELLocalizationUniProt · AlphaFold · HPA
Whether an antibody against GFRAL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.39
- Highest tissue expression
- 0.3 nTPM
Expression across tissuesHPA
Tissue
- liver: 0.3 nTPM
- adipose tissue: 0.1 nTPM
- testis: 0.1 nTPM
- adrenal gland: 0 nTPM
- amygdala: 0 nTPM
- appendix: 0 nTPM
Single-cell type
- fibro-adipogenic progenitors: 9.9 nCPM
- hepatic stellate cells: 6.5 nCPM
- bergmann glia: 4.8 nCPM
- epicardial cells: 4.5 nCPM
- pituitary stem cells: 4.2 nCPM
- pericytes: 3 nCPM
Immune cell
- neutrophil: 0.2 nTPM
- basophil: 0.1 nTPM
- memory B-cell: 0.1 nTPM
- naive B-cell: 0.1 nTPM
- plasmacytoid DC: 0.1 nTPM
- classical monocyte: 0 nTPM
Brain region
- cerebellum: 1.1 nTPM
- cerebral cortex: 1.1 nTPM
- thalamus: 1.1 nTPM
- amygdala: 0.9 nTPM
- white matter: 0.9 nTPM
- basal ganglia: 0.8 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.26
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.63
- DepMap mean gene effect
- 0.13
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- GDF15-GFRAL signaling pathway
- negative regulation of appetite
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- negative regulation of neuron apoptotic process
- nervous system development
- positive regulation of MAPK cascade
- positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- reduction of food intake in response to dietary excess
- response to metformin
- stress-activated protein kinase signaling cascade
Molecular functions
- glial cell-derived neurotrophic factor receptor activity
- hormone activity
- receptor tyrosine kinase binding
- signaling receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of GFRAL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads GFRAL as an antibody target. Whether an autoantibody or antibody against GFRAL could matter depends on whether native GFRAL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
GFRAL is annotated at the cell surface, where native GFRAL is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label GFRAL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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