FGF21

Summary

FGF21 (fibroblast growth factor 21, HGNC:3678) is a protein-coding gene on chromosome 19q13.33, encoding Fibroblast growth factor 21 (Q9NSA1). Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression).

Theis gene encodes a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. This protein is a secreted endocrine factor that functions as a major metabolic regulator. The encoded protein stimulates the uptake of glucose in adipose tissue.

Source: NCBI Gene 26291 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_019113

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3678
Approved symbol	FGF21
Name	fibroblast growth factor 21
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105550
Ensembl biotype	protein_coding
OMIM	609436
Entrez	26291

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000222157, ENST00000593756

RefSeq mRNA: 1 — MANE Select: NM_019113 NM_019113

CCDS: CCDS12734

Canonical transcript exons

ENST00000593756 — 4 exons

Exon	Start	End
ENSE00001130538	48756926	48757029
ENSE00003070481	48757930	48758330
ENSE00003147212	48755891	48756471
ENSE00003149416	48755524	48755784

Expression profiles

Bgee: expression breadth broad, 37 present calls, max score 86.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1660 / max 44.1708, expressed in 34 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176822	0.0766	14
176821	0.0509	11
176820	0.0384	8

Top tissues by expression

262 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	86.00	gold quality
liver	UBERON:0002107	76.76	gold quality
type B pancreatic cell	CL:0000169	75.83	gold quality
olfactory bulb	UBERON:0002264	75.55	gold quality
triceps brachii	UBERON:0001509	75.06	gold quality
gluteal muscle	UBERON:0002000	74.38	gold quality
pancreatic ductal cell	CL:0002079	74.14	silver quality
cervix squamous epithelium	UBERON:0006922	72.91	gold quality
parotid gland	UBERON:0001831	72.46	gold quality
vena cava	UBERON:0004087	71.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.62	gold quality
thymus	UBERON:0002370	70.57	gold quality
nasal cavity epithelium	UBERON:0005384	69.75	gold quality
body of tongue	UBERON:0011876	69.29	gold quality
vastus lateralis	UBERON:0001379	69.21	gold quality
lateral globus pallidus	UBERON:0002476	69.00	gold quality
pharyngeal mucosa	UBERON:0000355	68.70	gold quality
male germ cell	CL:0000015	68.64	gold quality
trachea	UBERON:0003126	68.01	gold quality
myocardium	UBERON:0002349	67.99	gold quality
heart right ventricle	UBERON:0002080	67.77	gold quality
tongue	UBERON:0001723	67.76	gold quality
sperm	CL:0000019	67.67	gold quality
subthalamic nucleus	UBERON:0001906	67.65	gold quality
saphenous vein	UBERON:0007318	67.56	gold quality
inferior vagus X ganglion	UBERON:0005363	67.36	gold quality
nipple	UBERON:0002030	67.28	gold quality
pericardium	UBERON:0002407	67.14	gold quality
substantia nigra pars reticulata	UBERON:0001966	67.13	gold quality
cardia of stomach	UBERON:0001162	67.11	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ATF2, ATF4, BHLHA15, CREB3L3, DNMT3A, MLXIPL, NFE2L2, NFIL3, NR1D1, NR1H2, NR1H3, NR4A1, PPARA, PPARG, PPARGC1A, RORA, RXRA, SP1, SREBF1, STAT5A, TCF23, TCF3, THRB

miRNA regulators (miRDB)

12 targeting FGF21, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-4680-5P	96.43	67.15	893

Literature-anchored findings (GeneRIF, showing 40)

• When administered daily for 6 wk to diabetic rhesus monkeys, FGF-21 caused a dramatic decline in fasting plasma glucose, fructosamine, triglycerides, insulin, and glucagon. (PMID:17068132)
• klotho beta functions as a cofactor essential for FGF21 activity (PMID:17452648)
• work suggests a potential role for Fibroplast growth factor 21(FGF-21) in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM) (PMID:17926232)
• FGF21 is a novel adipokine associated with obesity-related metabolic complications in humans. (PMID:18252893)
• reduced plasma FGF21 levels could be involved in the pathophysiology of anorexia nervosa or in a complex adaptive response to this disease. (PMID:18559909)
• The wide interindividual variation and the induction of ketogenesis independent of FGF21 levels indicate that the physiological role of FGF21 in humans may differ from that in mice. (PMID:18680716)
• Data show that increasing concentrations of FGF-21 were independently and significantly associated with T2DM and T2DK. The work suggests that FGF-21 may play a role in the pathogenesis of T2DM and T2DK. (PMID:18722685)
• Both FGF23 and FGF21 require intact alpha or betaKlotho for signaling, respectively, whereas FGF19 can signal through a Klotho chimera consisting of the N terminus of alphaKlotho and the C terminus of betaKlotho. (PMID:18829467)
• FGF21 serum levels increase in chronic hemodialysis patients and are related to markers of renal function in control subjects (PMID:18840768)
• These data demonstrate that the C-terminus of FGF21 is critical for binding to beta-Klotho and the N-terminus is critical for fibroblast growth factor receptor (FGFR) activation. (PMID:19059246)
• Serum levels of FGF21 are closely related to adiposity, lipid metabolism, and biomarkers of liver injury but not insulin secretion and sensitivity in humans. (PMID:19318452)
• Results offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity. (PMID:19401423)
• Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. (PMID:19487637)
• Rosiglitazone may play a role in lowering FGF-21 levels in T2 Diabetes mellitus patients. (PMID:19528204)
• FGF21 does not play a major role in regulating the fasting response or ketosis in man. (PMID:19531592)
• Report increased FGF21 concentrations in both patients with Cushing’s syndrome and obesity relative to lean subjects. (PMID:19681655)
• Fibroblast growth factor 21 is independently associated with markers of insulin resistance and an adverse lipid profile but is not dysregulated in GDM if patients are matched with controls for fasting insulin (PMID:19699495)
• Serum and tissue expression of FGF21 levels were significantly higher in both obese and T2DM patients relative to controls. (PMID:19702724)
• FGF-21 is expressed in human skeletal muscle in response to insulin stimulation, suggesting that FGF-21 is an insulin-regulated myokine. In support, we found an association between chronic hyperinsulinemia and levels of FGF-21. (PMID:19720803)
• FGF-21 may mediate a state of growth hormone resistance in anorexia nervosa. (PMID:19926712)
• a clear link between RORalpha, a key regulator of the mammalian clock, and FGF21, an important hormone regulating glucose and lipid homeostasis. (PMID:20332535)
• The finding that moderate weight loss did not induce changes of FGF-21 levels in humans suggests that FGF-21 is not directly regulated by fat mass. (PMID:20362303)
• FGF21 correlates with BMI and may be a novel biomarker for nonalcoholic fatty liver disease, but is not nutritionally regulated in humans. (PMID:20451522)
• serum FGF21 levels were biochemical indicators correlating to a set of essential metabolic parameters, which was distinct from that correlating to serum adiponectin levels in subjects with type 2 diabetes (PMID:20452080)
• the purified hFGF-21 could stimulate glucose uptake in a dose-dependent manner, and glucose transporters (GLUT1) is the functional unit. (PMID:20566462)
• There is an independent association between serum FGF21 levels and fasting plasma glucose, body mass index, uric acid, and physical activity. (PMID:20566587)
• FGF-21 is an independent risk factor for abdominal obesity. (PMID:20629328)
• role of FGF21 as a key regulator of hepatic lipid metabolism in humans, and suggest that serum FGF21 can be potentially used as a biomarker for NAFLD. (PMID:20675007)
• Impact of diet-induced obesity on human FGF21 signaling and resultant transcriptional events in liver and white adipose tissue in mice. (PMID:20682689)
• Common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk. (PMID:20717167)
• high liver fat and triglycerides rather than overall adiposity associate with high FGF21 levels (PMID:21123446)
• FGF-21 serum levels are increased in coronary heart disease patients and are independently associated with adverse lipid profile (PMID:21206918)
• Plasma FGF21 is increased in T2D patients, and positively correlated with fasting insulin and BMI. FGF21 has direct effects in enhancing skeletal muscle glucose uptake (PMID:21309058)
• Finding opens new routes for the potential use of pharmaceuticals that could induce FGF21 and, hence, activate BAT thermogenesis. (PMID:21373720)
• Human HMGCS2 regulates mitochondrial fatty acid oxidation and FGF21 expression (PMID:21502324)
• FGF21 is a metabolic hormone that is regulated by nutritional status and influences glucose and lipid metabolism. (PMID:21505329)
• A 3-month combined exercise programme decreases the FGF21 levels as well as arterial stiffness in obese Korean women. (PMID:21521346)
• Plasma FGF21 follows a circadian rhythm during a 72-h fast in healthy female subjects. The circadian regulation has a stronger impact on plasma FGF21 than the fasting status over 72-h period. (PMID:21521350)
• Plasma FGF21 levels are significantly increased with the development of early- to end-stage chronic kidney disease and are independently associated with renal function and adverse lipid profiles in Chinese population. (PMID:21525989)
• Serum levels of FGF21 are closely related to liver steatosis in newly diagnosed type 2 DM patients. (PMID:21596453)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fgf21	ENSMUSG00000030827
rattus_norvegicus	Fgf21	ENSRNOG00000020990

Paralogs (21): FGF10 (ENSG00000070193), FGF22 (ENSG00000070388), FGF4 (ENSG00000075388), FGF20 (ENSG00000078579), FGF14 (ENSG00000102466), FGF9 (ENSG00000102678), FGF8 (ENSG00000107831), FGF6 (ENSG00000111241), FGF1 (ENSG00000113578), FGF12 (ENSG00000114279), FGF23 (ENSG00000118972), FGF13 (ENSG00000129682), FGF5 (ENSG00000138675), FGF2 (ENSG00000138685), FGF7 (ENSG00000140285), FGF18 (ENSG00000156427), FGF17 (ENSG00000158815), FGF11 (ENSG00000161958), FGF19 (ENSG00000162344), FGF3 (ENSG00000186895), FGF16 (ENSG00000196468)

Protein

Protein identifiers

Fibroblast growth factor 21 — Q9NSA1 (reviewed: Q9NSA1)

All UniProt accessions (2): Q9NSA1, A0A7U3L5M7

UniProt curated annotations — full annotation on UniProt →

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. Regulates systemic glucose homeostasis and insulin sensitivity.

Subunit / interactions. Interacts (via C-terminus) with KLB; this interaction is direct. Interacts with FGFR4.

Subcellular location. Secreted.

Similarity. Belongs to the heparin-binding growth factors family.

RefSeq proteins (1): NP_061986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily
IPR035444	FGF15/19/21	Family

Pfam: PF00167

UniProt features (25 total): strand 12, helix 3, turn 3, sequence variant 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5VAQ	X-RAY DIFFRACTION	2.61
6M6E	SOLUTION NMR
6M6F	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSA1-F1	77.51	0.48

Antibody-complex structures (SAbDab): 1 — 5VAQ

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-189200	Cellular hexose transport
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes

MSigDB gene sets: 133 (showing top): GOBP_CARBOHYDRATE_TRANSPORT, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_LOW_DENSITY_LIPOPROTEIN_PARTICLE_CLEARANCE, GOBP_CELL_CELL_SIGNALING, GOBP_PLASMA_LIPOPROTEIN_PARTICLE_CLEARANCE, KEGG_PATHWAYS_IN_CANCER, GOBP_RESPONSE_TO_FIBROBLAST_GROWTH_FACTOR, GOBP_D_GLUCOSE_IMPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_RESPONSE_TO_GROWTH_FACTOR

GO Biological Process (12): signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), regulation of low-density lipoprotein particle clearance (GO:0010988), neurogenesis (GO:0022008), regulation of cell migration (GO:0030334), positive regulation of MAPK cascade (GO:0043410), positive regulation of D-glucose import across plasma membrane (GO:0046326), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway (GO:0090080), positive regulation of cold-induced thermogenesis (GO:0120162)

GO Molecular Function (3): fibroblast growth factor receptor binding (GO:0005104), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Plasma lipoprotein remodeling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
MAPK cascade	2
positive regulation of MAPK cascade	2
cellular anatomical structure	2
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
regulation of lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
nervous system development	1
cell differentiation	1
cell migration	1
regulation of cell motility	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
fibroblast growth factor receptor signaling pathway	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
growth factor receptor binding	1
receptor ligand activity	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2114 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF21	KLB	Q86Z14	999
FGF21	FGFR1	P11362	986
FGF21	KL	Q9UEF7	979
FGF21	FGFR4	P22455	977
FGF21	PPARA	Q07869	861
FGF21	FGFR3	P22607	815
FGF21	INS	P01308	802
FGF21	UCP1	P25874	793
FGF21	ADIPOQ	Q15848	781
FGF21	FNDC5	Q8NAU1	774
FGF21	PPARGC1A	Q9UBK2	762
FGF21	ADRB3	P13945	762
FGF21	FGFR2	P18443	748
FGF21	LEP	P41159	727
FGF21	PPARG	P37231	698

IntAct

38 interactions, top by confidence:

A	B	Type	Score
HSPA2	FGF21	psi-mi:“MI:0915”(physical association)	0.610
SGTA	FGF21	psi-mi:“MI:0915”(physical association)	0.560
	FGF21	psi-mi:“MI:0915”(physical association)	0.560
SGTB	FGF21	psi-mi:“MI:0915”(physical association)	0.560
FGF21	CASP6	psi-mi:“MI:0915”(physical association)	0.560
FGF21	FKBP1A	psi-mi:“MI:0915”(physical association)	0.560
FGF21	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	FGF21	psi-mi:“MI:0915”(physical association)	0.560
FGF21	BAG6	psi-mi:“MI:0915”(physical association)	0.560
KLF11	FGF21	psi-mi:“MI:0915”(physical association)	0.560
KLB	FGF21	psi-mi:“MI:0407”(direct interaction)	0.440
TNS2	FGF21	psi-mi:“MI:0915”(physical association)	0.370
FGF21	CDC25A	psi-mi:“MI:0915”(physical association)	0.370
FGF21	CDH7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (12): FGF21 (Two-hybrid), FGF21 (Two-hybrid), FGF21 (Two-hybrid), SGTB (Two-hybrid), FGF21 (Affinity Capture-Western), NFE2L2 (Affinity Capture-Western), FGF21 (Reconstituted Complex), FGF21 (Reconstituted Complex), FGF21 (Affinity Capture-RNA), MAPK7 (Two-hybrid), FGF21 (Two-hybrid), FGF21 (Two-hybrid)

ESM2 similar proteins: A5A8Y8, A7MBM2, E9PY61, O08542, O08545, O08717, O43921, O75888, O77805, O77835, P04087, P05111, P07434, P07994, P17490, P34820, P43031, P52794, P52797, P52798, P52801, P55101, P58166, Q16586, Q24JP5, Q28686, Q5Q0T9, Q5RJL6, Q5SZI1, Q641Q3, Q6PGN1, Q6PRD1, Q6ZVN8, Q7TQ32, Q7Z5Y6, Q80WF4, Q8C1Q4, Q8K1S7, Q8N7M5, Q8NCW0

Diamond homologs: O15520, O35565, O35622, O95750, P05524, P11487, P21781, P36363, P36386, P48801, P48802, P48805, P48806, P48808, P70377, P70379, P70492, P79150, Q02195, Q5D0X0, Q5RAY8, Q5RDS9, Q8R5L7, Q8VI82, Q92913, Q92915, Q9EPC2, Q9ERW3, Q9ESS2, Q9GZV9, Q9JJN1, Q9N198, Q9NSA1, A0MTF4, A6P7H6, M3X9S6, O43320, O54769, O76093, O88182

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ATF2	“up-regulates quantity by expression”	FGF21	“transcriptional regulation”
ATF4	“up-regulates quantity by expression”	FGF21	“transcriptional regulation”
DNMT3A	“down-regulates quantity by repression”	FGF21	“transcriptional regulation”
TFEB	“up-regulates quantity by expression”	FGF21	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

53 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

431 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48756924:A:AG	acceptor_gain	1.0000
19:48756924:AG:A	acceptor_gain	1.0000
19:48756925:G:GA	acceptor_gain	1.0000
19:48756925:GG:G	acceptor_gain	1.0000
19:48756925:GGT:G	acceptor_gain	1.0000
19:48756925:GGTC:G	acceptor_gain	1.0000
19:48756925:GGTCT:G	acceptor_gain	1.0000
19:48757027:TCGGT:T	donor_loss	1.0000
19:48757030:G:C	donor_loss	1.0000
19:48757030:G:GG	donor_gain	1.0000
19:48757031:TGAG:T	donor_loss	1.0000
19:48757928:A:AG	acceptor_gain	1.0000
19:48757929:G:GG	acceptor_gain	1.0000
19:48757929:GCTC:G	acceptor_gain	1.0000
19:48757929:GCTCC:G	acceptor_gain	1.0000
19:48756428:G:GT	donor_gain	0.9900
19:48756429:G:T	donor_gain	0.9900
19:48756468:GAAA:G	donor_gain	0.9900
19:48756470:AA:A	donor_gain	0.9900
19:48756470:AAGT:A	donor_loss	0.9900
19:48756472:G:GG	donor_gain	0.9900
19:48756917:A:AG	acceptor_gain	0.9900
19:48756918:C:G	acceptor_gain	0.9900
19:48757025:GATCG:G	donor_gain	0.9900
19:48757026:ATCG:A	donor_gain	0.9900
19:48757027:TCG:T	donor_gain	0.9900
19:48757032:GAG:G	donor_loss	0.9900
19:48757920:T:TA	acceptor_gain	0.9900
19:48757926:CTAGC:C	acceptor_loss	0.9900
19:48757927:TAGCT:T	acceptor_loss	0.9900

AlphaMissense

1319 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48757958:T:C	F123S	0.995
19:48757958:T:G	F123C	0.995
19:48756991:T:C	F101L	0.994
19:48756993:C:A	F101L	0.994
19:48756993:C:G	F101L	0.994
19:48756968:T:C	I93T	0.992
19:48756424:T:C	I63T	0.990
19:48756999:C:G	C103W	0.990
19:48757952:G:A	C121Y	0.990
19:48757993:T:G	Y135D	0.990
19:48756998:G:A	C103Y	0.989
19:48757953:C:G	C121W	0.989
19:48757957:T:C	F123L	0.988
19:48757959:C:A	F123L	0.988
19:48757959:C:G	F123L	0.988
19:48758081:T:C	F164S	0.988
19:48757951:T:A	C121S	0.987
19:48757952:G:C	C121S	0.987
19:48756436:G:T	G67V	0.986
19:48756997:T:A	C103S	0.986
19:48756998:G:C	C103S	0.986
19:48758080:T:C	F164L	0.986
19:48758082:C:A	F164L	0.986
19:48758082:C:G	F164L	0.986
19:48757025:G:A	G112E	0.985
19:48757952:G:T	C121F	0.982
19:48757993:T:A	Y135N	0.982
19:48758081:T:G	F164C	0.982
19:48756995:T:A	L102Q	0.980
19:48756997:T:C	C103R	0.980

dbSNP variants (sampled 300 via entrez): RS1000350304 (19:48754323 T>C), RS1000666062 (19:48758612 G>A,T), RS1000789993 (19:48758243 C>T), RS1001098075 (19:48758477 T>C), RS1001259416 (19:48754010 C>A,T), RS1001292048 (19:48753723 G>A,T), RS1002370172 (19:48757425 G>A), RS1002871452 (19:48758283 T>C), RS1003159434 (19:48757166 C>A,T), RS1004645117 (19:48758561 G>C), RS1004710578 (19:48753713 G>A), RS1004787941 (19:48754958 G>A), RS1004954214 (19:48758787 A>G), RS1005209068 (19:48753978 G>A), RS1006213222 (19:48757796 C>G,T)

Disease associations

OMIM: gene MIM:609436 | disease phenotypes: MIM:135700

GenCC curated gene-disease

Mondo (1): congenital fibrosis of extraocular muscles (MONDO:0007614)

Orphanet (1): Congenital fibrosis of extraocular muscles (Orphanet:45358)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000847_1	Retinal vascular caliber	2.000000e-25
GCST001241_6	Bipolar disorder	3.000000e-06
GCST001844_2	Dietary macronutrient intake	8.000000e-09
GCST001988_3	Dietary macronutrient intake	3.000000e-07
GCST001988_5	Dietary macronutrient intake	4.000000e-10
GCST004523_5	Resting metabolic rate	5.000000e-06
GCST006388_3	Dietary macronutrient intake	9.000000e-23
GCST006388_4	Dietary macronutrient intake	1.000000e-19
GCST006388_5	Dietary macronutrient intake	5.000000e-28
GCST006613_46	Triglycerides	8.000000e-13
GCST008555_4	Breakfast cereal skipping frequency	2.000000e-08
GCST008556_4	Breakfast skipping	2.000000e-08
GCST008647_36	Urinary sodium excretion	5.000000e-11
GCST010132_5	Processed meat consumption	2.000000e-11
GCST010134_4	Non-oily fish consumption	3.000000e-16
GCST010135_4	Oily fish consumption	2.000000e-16
GCST010136_42	Fruit consumption	3.000000e-10
GCST010137_4	Cooked vegetable consumption	3.000000e-09
GCST010140_48	Pork consumption	2.000000e-16
GCST010142_1	Fish- and plant-related diet	7.000000e-13
GCST010142_45	Fish- and plant-related diet	3.000000e-08
GCST010142_68	Fish- and plant-related diet	6.000000e-10
GCST010143_10	Meat-related diet	4.000000e-09
GCST010143_20	Meat-related diet	8.000000e-12
GCST010173_29	Triglyceride levels	9.000000e-18
GCST010244_59	Triglyceride levels	2.000000e-33
GCST010496_4	Relative sugar intake	3.000000e-20
GCST010497_7	Relative carbohydrate intake	7.000000e-15
GCST010498_5	Relative protein intake	4.000000e-26
GCST90016669_12	Pancreas volume	1.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004731	eye measurement
EFO:0003939	energy intake
EFO:0008004	resting metabolic rate measurement
EFO:0004530	triglyceride measurement
EFO:0010129	breakfast skipping measurement
EFO:0009282	sodium measurement
EFO:0008111	diet measurement
EFO:0010158	sugar consumption measurement
EFO:0010811	carbohydrate intake measurement
EFO:0010810	protein intake measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580012	congenital fibrosis of the extraocular muscles (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
nuciferine	increases expression, decreases expression, increases reaction, decreases reaction	2
Acetaminophen	increases expression, decreases expression	2
Dithiothreitol	increases expression, decreases reaction	2
Glucose	affects uptake, increases expression, decreases reaction	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Palmitic Acid	affects cotreatment, increases expression, increases reaction, decreases expression, decreases reaction	2
bisphenol A	affects expression	1
trichostatin A	increases expression	1
citreoviridin	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression, decreases reaction, decreases secretion, decreases stability	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	increases expression	1
imidazopyrazole	affects expression	1
indolo(3,2-b)carbazole	decreases reaction, increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
arachidonyl-2-chloroethylamide	affects reaction, decreases reaction, increases expression	1
GW 7647	decreases reaction, increases expression	1
dorsomorphin	decreases reaction, increases expression	1
SRT1720	increases expression	1
neohesperidin	increases expression	1
GSK5182	decreases reaction, increases expression	1
Bortezomib	increases expression, increases response to substance	1
Rosiglitazone	increases expression	1
Resveratrol	increases expression	1
Pioglitazone	increases expression	1
Acetylcysteine	decreases expression, decreases reaction, decreases secretion	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1S9	SEES3-1V human FGF21, clone1	Embryonic stem cell	Male
CVCL_A1T0	SEES3-1V human FGF21, clone2	Embryonic stem cell	Male
CVCL_A1T1	SEES3-1V human FGF21, clone3	Embryonic stem cell	Male
CVCL_B9VI	Abcam HeLa FGF21 KO	Cancer cell line	Female

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies