FFAR1

protein-coding

free fatty acid receptor 1, the group of Free fatty acid receptors

Gene summary

This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for medium and long chain free fatty acids and may be involved in the metabolic regulation of insulin secretion. Polymorphisms in this gene may be associated with type 2 diabetes. [provided by RefSeq, Apr 2009]

Previous symbols:

GPR40

MANE transcript

NM_005303.3

Inheritance

—

ClinVar variants

U:46B:2

Top phenotype

Hypercholesterolemia, familial, 1

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr19:35,347,902-35,353,864

External References & Databases

Ensembl (ENSG00000126266)

Transcript & Mutation Effects

hg38 • Region Span ~6.0 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 FFAR1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 48

Hypercholesterolemia, familial, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005303.3. 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						0
missense			46 clinvar	2 clinvar		48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	2	0	48

Highest pathogenic variant AF is 0.0000028762495

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005303.3	RefSeq	NP_005294.1	1	MANE Select
ENST00000246553.4	Ensembl	ENSP00000246553.2	1	MANE Select
ENST00000950226.1	Ensembl	ENSP00000620285.1	1	Standard
ENST00000950226.2	Ensembl	ENSP00000620285.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin secretion - Homo sapiens (human)
GPR40 Pathway
GPCRs, Class A Rhodopsin-like
Signaling by GPCR
Signal Transduction

Biological Process

G protein-coupled receptor signaling pathway
insulin secretion
positive regulation of insulin secretion
glucose homeostasis
positive regulation of calcium ion transport

Molecular Function

G protein-coupled receptor activity
guanyl-nucleotide exchange factor activity
lipid binding
bioactive lipid receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246553
Coding exons: 1
Length: 923
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.612	166	190	0.875	0.0000139	1797
Missense (PolyPhen)		64	69.172	0.92523		674
Synonymous	0.209	97	99.7	0.973	0.00000786	715
Loss of Function	0.376	5	5.99	0.834	3.47e-7	52

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose- stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor signaling activates pathways that inhibit osteoclast differentiation (By similarity). Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway. {ECO:0000250|UniProtKB:Q76JU9, ECO:0000269|PubMed:12496284, ECO:0000269|PubMed:17699519, ECO:0000269|PubMed:24130766}.;

Recessive Scores

pRec: 0.129

Intolerance Scores

LoFtool: 0.703
RVIS EVS: 0.24
RVIS percentile EVS: 69.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.224

Gene Damage Prediction

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