GFRA1

GDNF family receptor alpha 1

Basic information

Region (hg38): 10:116056924-116276803

Previous symbols: [ "GDNFRA" ]

Links

ENSG00000151892 ∙ NCBI:2674 ∙ OMIM:601496 ∙ HGNC:4243 ∙ Uniprot:P56159 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal hypodysplasia/aplasia 4 (Limited), mode of inheritance: AR
• renal hypodysplasia/aplasia 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal hypodysplasia/aplasia 4	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary; Renal	33020172; 34737117

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFRA1 gene.

• Inborn genetic diseases (17 variants)
• not provided (7 variants)
• Renal hypodysplasia/aplasia 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFRA1 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				4	1	5
missense			18	1	1	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	5	2

Variants in GFRA1

This is a list of pathogenic ClinVar variants found in the GFRA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-116064404-T-C		GFRA1-related disorder	Likely benign (Feb 19, 2019)
10-116064452-C-G			Likely benign (Jul 20, 2018)
10-116064501-GT-G		Renal hypodysplasia/aplasia 4	Pathogenic (May 24, 2022)
10-116065565-A-C		GFRA1-related disorder	Likely benign (Jun 10, 2019)
10-116065595-T-C		not specified	Likely benign (May 08, 2023)
10-116065607-T-G		not specified	Uncertain significance (May 25, 2022)
10-116089768-A-T		not specified	Uncertain significance (Nov 28, 2023)
10-116089793-C-G		not specified	Uncertain significance (Jul 20, 2021)
10-116089842-T-C		GFRA1-related disorder	Benign (Oct 21, 2019)
10-116089901-C-T		not specified	Uncertain significance (Mar 29, 2023)
10-116093715-G-A		GFRA1-related disorder	Benign (Feb 19, 2019)
10-116096646-G-A		GFRA1-related disorder	Likely benign (Jul 02, 2019)
10-116096674-G-A			Likely benign (Jul 12, 2018)
10-116096687-G-T		not specified	Uncertain significance (Mar 02, 2023)
10-116096688-C-T		not specified	Uncertain significance (Mar 02, 2023)
10-116096704-A-G			Likely benign (Mar 02, 2018)
10-116096731-C-A		not specified	Uncertain significance (Nov 09, 2022)
10-116096753-G-A		not specified	Uncertain significance (Sep 14, 2023)
10-116096756-A-G		Hirschsprung disease, susceptibility to, 1	Uncertain significance (Apr 01, 2015)
10-116096759-C-T		not specified	Uncertain significance (Mar 16, 2022)
10-116125216-C-A		GFRA1-related disorder	Likely benign (May 23, 2019)
10-116125236-G-A		GFRA1-related disorder	Likely benign (Mar 21, 2019)
10-116125237-T-C		not specified	Uncertain significance (Oct 27, 2023)
10-116125244-G-A		GFRA1-related disorder	Benign/Likely benign (Feb 01, 2024)
10-116125266-T-C		not specified	Uncertain significance (Sep 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFRA1	protein_coding	protein_coding	ENST00000355422	10	216536

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.117	0.882	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	214	280	0.766	0.0000158	3046
Missense in Polyphen		48	84.405	0.56868		917
Synonymous	-0.967	133	120	1.11	0.00000737	895
Loss of Function	3.24	6	22.6	0.265	0.00000104	270

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor (By similarity). {ECO:0000250}.
• Pathway: Exercise-induced Circadian Regulation;Developmental Biology;Signal Transduction;IL-7 signaling;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;NCAM signaling for neurite out-growth;Posttranslational regulation of adherens junction stability and dissassembly;EPO signaling;Signaling events regulated by Ret tyrosine kinase;NCAM1 interactions;RET signaling;Axon guidance;VEGF (Consensus)

Recessive Scores

• pRec: 0.184

Intolerance Scores

• loftool: 0.565
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.34

Haploinsufficiency Scores

• pHI: 0.286
• hipred: Y
• hipred_score: 0.748
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.510

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gfra1
• Phenotype: 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); cellular 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); muscle phenotype; digestive/alimentary phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; renal/urinary system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: gfra1a
• Affected structure: enteric neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: MAPK cascade;cell surface receptor 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;extracellular exosome
• Molecular function: Ras guanyl-nucleotide exchange factor activity;signaling receptor binding;glial cell-derived neurotrophic factor receptor activity