GFRA2

GDNF family receptor alpha 2

Basic information

Region (hg38): 8:21690397-21812357

Links

ENSG00000168546 ∙ NCBI:2675 ∙ OMIM:601956 ∙ HGNC:4244 ∙ Uniprot:O00451 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFRA2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFRA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			29	1	1	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	29	1	2

Variants in GFRA2

This is a list of pathogenic ClinVar variants found in the GFRA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-21693313-C-T		not specified	Uncertain significance (Jul 13, 2021)
8-21693326-C-T			Benign (Nov 29, 2017)
8-21693346-G-A			Benign (Apr 24, 2018)
8-21693351-G-A		not specified	Uncertain significance (Apr 05, 2023)
8-21693371-G-C		not specified	Likely benign (May 27, 2022)
8-21693388-T-C		not specified	Uncertain significance (Jun 24, 2022)
8-21693396-G-A		not specified	Uncertain significance (Aug 10, 2021)
8-21702881-G-A		not specified	Uncertain significance (Dec 17, 2023)
8-21702894-G-A		not specified	Uncertain significance (Oct 03, 2022)
8-21702974-T-C		not specified	Uncertain significance (Jun 07, 2023)
8-21705039-T-C		not specified	Uncertain significance (May 26, 2023)
8-21705045-C-T		not specified	Uncertain significance (Feb 27, 2024)
8-21705053-C-T		not specified	Uncertain significance (Jun 10, 2024)
8-21705994-G-A		not specified	Uncertain significance (Nov 21, 2023)
8-21705994-G-C		not specified	Uncertain significance (Sep 13, 2023)
8-21706000-T-C		not specified	Uncertain significance (Oct 30, 2023)
8-21706004-A-C		not specified	Uncertain significance (Oct 12, 2022)
8-21706037-G-A		not specified	Uncertain significance (Feb 15, 2023)
8-21750589-G-A		not specified	Uncertain significance (Aug 17, 2022)
8-21750607-G-A		not specified	Uncertain significance (Aug 15, 2023)
8-21750607-G-C		not specified	Uncertain significance (Dec 06, 2021)
8-21750637-G-A		not specified	Uncertain significance (Jul 26, 2021)
8-21750640-T-G		not specified	Uncertain significance (Apr 18, 2023)
8-21750654-T-A		not specified	Uncertain significance (Dec 19, 2022)
8-21750657-G-A		Pazopanib response	drug response (Jul 16, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFRA2	protein_coding	protein_coding	ENST00000524240	9	121955

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0975	0.896	124646	0	6	124652	0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.141	191	197	0.972	0.0000129	3011
Missense in Polyphen		49	68.737	0.71287		1014
Synonymous	-1.44	100	83.3	1.20	0.00000568	914
Loss of Function	2.36	4	13.3	0.302	7.27e-7	237

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000592	0.0000592
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000282	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.0000343	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.
• Pathway: Developmental Biology;Signal Transduction;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;NCAM signaling for neurite out-growth;NCAM1 interactions;RET signaling;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.145

Haploinsufficiency Scores

• pHI: 0.318
• hipred: N
• hipred_score: 0.361
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.865

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Gfra2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: MAPK cascade;transmembrane receptor protein tyrosine kinase signaling pathway;nervous system development;axon guidance;glial cell-derived neurotrophic factor receptor signaling pathway
• Cellular component: plasma membrane;external side of plasma membrane;extrinsic component of membrane;anchored component of membrane;receptor complex
• Molecular function: Ras guanyl-nucleotide exchange factor activity;glial cell-derived neurotrophic factor receptor activity