FGF21

fibroblast growth factor 21, the group of Fibroblast growth factor family

Basic information

Region (hg38): 19:48755523-48758333

Links

ENSG00000105550 ∙ NCBI:26291 ∙ OMIM:609436 ∙ HGNC:3678 ∙ Uniprot:Q9NSA1 ∙ 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 FGF21 gene.

• Inborn genetic diseases (17 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF21 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				2	2	4
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	2	2

Variants in FGF21

This is a list of pathogenic ClinVar variants found in the FGF21 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-48756245-G-A			Likely benign (May 25, 2018)
19-48756248-C-T			Benign (Jul 19, 2018)
19-48756369-C-T		Congenital fibrosis of extraocular muscles	Uncertain significance (Feb 26, 2024)
19-48756375-C-T		not specified	Uncertain significance (Dec 28, 2023)
19-48756381-C-A		not specified	Uncertain significance (Sep 21, 2023)
19-48756421-A-C		not specified	Uncertain significance (Jun 16, 2023)
19-48756432-G-A		not specified	Uncertain significance (Sep 22, 2022)
19-48756450-G-A		not specified	Uncertain significance (Aug 12, 2022)
19-48756953-C-T		not specified	Uncertain significance (Nov 05, 2021)
19-48756967-A-G		not specified	Uncertain significance (Nov 17, 2022)
19-48756993-C-G		not specified	Uncertain significance (Mar 21, 2023)
19-48757004-G-A		not specified	Uncertain significance (Mar 05, 2024)
19-48757028-C-G		not specified	Uncertain significance (Aug 01, 2022)
19-48757961-G-A		not specified	Uncertain significance (Apr 07, 2022)
19-48757984-T-C		not specified	Uncertain significance (Nov 03, 2023)
19-48758014-C-G		not specified	Uncertain significance (Nov 22, 2022)
19-48758034-G-T			Likely benign (Jun 06, 2018)
19-48758054-A-T		not specified	Uncertain significance (Aug 17, 2022)
19-48758062-C-G		not specified	Uncertain significance (Sep 26, 2023)
19-48758077-C-T		not specified	Uncertain significance (Dec 03, 2021)
19-48758098-C-G		not specified	Uncertain significance (Jan 17, 2024)
19-48758102-C-A		not specified	Uncertain significance (Aug 10, 2023)
19-48758107-G-C		not specified	Uncertain significance (Apr 12, 2022)
19-48758135-C-T		not specified	Uncertain significance (Jun 09, 2022)
19-48758174-G-A		not specified	Uncertain significance (May 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF21	protein_coding	protein_coding	ENST00000593756	3	2772

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0294	0.818	125740	0	7	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.296	139	130	1.07	0.00000818	1303
Missense in Polyphen		42	46.013	0.91278		519
Synonymous	-0.555	66	60.5	1.09	0.00000395	472
Loss of Function	1.10	3	5.89	0.509	2.51e-7	66

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000452	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. {ECO:0000269|PubMed:15902306, ECO:0000269|PubMed:17623664}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Melanoma - Homo sapiens (human);Breast cancer - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Aryl Hydrocarbon Receptor;MAPK Signaling Pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Plasma lipoprotein assembly, remodeling, and clearance;PI3K-Akt Signaling Pathway;Regulation of Actin Cytoskeleton;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;FGF;SLC-mediated transmembrane transport;Transport of small molecules;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Cellular hexose transport;GPCR signaling-G alpha i (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.183
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.56

Haploinsufficiency Scores

• pHI: 0.0790
• hipred: N
• hipred_score: 0.173
• ghis: 0.424

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.105

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgf21
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; skeleton 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); limbs/digits/tail phenotype; normal phenotype

Gene ontology

• Biological process: signal transduction;cell-cell signaling;positive regulation of cell population proliferation;regulation of signaling receptor activity;positive regulation of triglyceride catabolic process;regulation of low-density lipoprotein particle clearance;response to activity;endoplasmic reticulum unfolded protein response;response to nutrient levels;cellular response to drug;positive regulation of low-density lipoprotein particle receptor biosynthetic process;positive regulation of glucose import;positive regulation of ERK1 and ERK2 cascade;cellular response to glucose stimulus;cellular response to glucagon stimulus;cellular response to low-density lipoprotein particle stimulus;endothelial cell apoptotic process;positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway;positive regulation of cold-induced thermogenesis;negative regulation of neuron death;response to methionine;negative regulation of endothelial cell apoptotic process
• Cellular component: extracellular region;extracellular space;cell
• Molecular function: fibroblast growth factor receptor binding;protein binding;growth factor activity