GFRAL

GDNF family receptor alpha like

Basic information

Region (hg38): 6:55327469-55402493

Previous symbols: [ "C6orf144" ]

Links

ENSG00000187871 ∙ NCBI:389400 ∙ OMIM:617837 ∙ HGNC:32789 ∙ Uniprot:Q6UXV0 ∙ 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 GFRAL gene.

• not_specified (62 variants)
• not_provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFRAL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000207410.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			59	3		62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	59	3	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFRAL	protein_coding	protein_coding	ENST00000340465	9	75025

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.52e-10	0.245	125709	0	33	125742	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.630	230	205	1.12	0.00000976	2609
Missense in Polyphen		59	51.828	1.1384		693
Synonymous	0.0537	69	69.6	0.992	0.00000332	671
Loss of Function	0.698	16	19.3	0.829	8.11e-7	272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000189	0.000185
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Brainstem-restricted receptor for GDF15 which regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). Upon interaction with its ligand, GDF15, interacts with RET and induces cellular signaling through activation of MAPK- and AKT- signaling pathways. {ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886}.

Recessive Scores

• pRec: 0.0689

Intolerance Scores

• loftool: 0.881
• rvis_EVS: 0.95
• rvis_percentile_EVS: 90.06

Haploinsufficiency Scores

• pHI: 0.123
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.171

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gfral
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: activation of MAPK activity;reduction of food intake in response to dietary excess;nervous system development;stress-activated protein kinase signaling cascade;glial cell-derived neurotrophic factor receptor signaling pathway;positive regulation of MAPK cascade;negative regulation of neuron apoptotic process;positive regulation of protein kinase B signaling;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: external side of plasma membrane;integral component of membrane;receptor complex
• Molecular function: protein binding;glial cell-derived neurotrophic factor receptor activity;receptor tyrosine kinase binding