GFRAL

protein-coding

GDNF family receptor alpha like

Gene summary

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 plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C6orf144

MANE transcript

NM_207410.2

Inheritance

—

ClinVar variants

U:62B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr6:55,327,469-55,402,493

External References & Databases

Ensembl (ENSG00000187871)

Transcript & Mutation Effects

hg38 • Region Span ~75.0 kb

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GenCC 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 GFRAL variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207410.2. 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 clinvar	1
missense			62 clinvar	4 clinvar		66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	4	1	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207410.2	RefSeq	NP_997293.2	9	MANE Select
ENST00000340465.2	Ensembl	ENSP00000343636.2	9	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

protein binding
glial cell-derived neurotrophic factor receptor activity
receptor tyrosine kinase binding

Cellular Component

external side of plasma membrane
integral component of membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340465
Coding exons: 9
Length: 75025
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125742
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.630	230	205	1.12	0.00000976	2609
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.171

Gene Damage Prediction

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