GFRA3
protein-codingGDNF family receptor alpha 3
Gene summary
The protein encoded by this gene is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor and a member of the GDNF receptor family. It forms a signaling receptor complex with RET tyrosine kinase receptor and binds the ligand, artemin. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GFRA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001496.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 47 | 3 | 50 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 47 | 4 | 1 | 52 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001487.2 | 8 | MANE Select | |
| Ensembl | ENSP00000274721.3 | 8 | MANE Select | |
| Ensembl | ENSP00000367613.3 | 7 | Standard | |
| Ensembl | ENSP00000367613.3 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gfra3 | Danio rerio | Structure: adductor hyohyoid Quality: lacks parts or has fewer parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Developmental Biology
- Signal Transduction
- RAF/MAP kinase cascade
- MAPK1/MAPK3 signaling
- MAPK family signaling cascades
Biological Process
- MAPK cascade
- neuron migration
- signal transduction
- nervous system development
- axon guidance
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- signaling receptor binding
- protein binding
- axon guidance receptor activity
Cellular Component
- cytosol
- plasma membrane
- external side of plasma membrane
- extrinsic component of membrane
- anchored component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274721
- Coding exons
- 8
- Length
- 22293
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.05 | 153 | 243 | 0.630 | 0.0000146 | 2587 |
| Missense (PolyPhen) | 44 | 92.368 | 0.47635 | 1011 | ||
| Synonymous | 0.837 | 87 | 97.5 | 0.892 | 0.00000582 | 812 |
| Loss of Function | 2.69 | 6 | 18.5 | 0.324 | 0.00000105 | 190 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000054 | 0.000046 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for the glial cell line-derived neurotrophic factor, ARTN (artemin). Mediates the artemin-induced autophosphorylation and activation of the RET receptor tyrosine kinase. {ECO:0000269|PubMed:9883723}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.472
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.802
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |