EGR3

Summary

EGR3 (early growth response 3, HGNC:3240) is a protein-coding gene on chromosome 8p21.3, encoding Early growth response protein 3 (Q06889). Probable transcription factor involved in muscle spindle development.

This gene encodes a transcriptional regulator that belongs to the EGR family of C2H2-type zinc-finger proteins. It is an immediate-early growth response gene which is induced by mitogenic stimulation. The protein encoded by this gene participates in the transcriptional regulation of genes in controling biological rhythm. It may also play a role in a wide variety of processes including muscle development, lymphocyte development, endothelial cell growth and migration, and neuronal development. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 1960 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 37 total
• Transcription factor: yes — 34 downstream targets (CollecTRI)
• MANE Select transcript: NM_004430

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3240
Approved symbol	EGR3
Name	early growth response 3
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	PILOT
Ensembl gene	ENSG00000179388
Ensembl biotype	protein_coding
OMIM	602419
Entrez	1960

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000317216, ENST00000518773, ENST00000519492, ENST00000522910, ENST00000524088

RefSeq mRNA: 2 — MANE Select: NM_004430 NM_001199880, NM_004430

CCDS: CCDS56528, CCDS6033

Canonical transcript exons

ENST00000317216 — 2 exons

Exon	Start	End
ENSE00001256735	22687659	22691482
ENSE00001329929	22692791	22693480

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 96.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5493 / max 3235.7903, expressed in 1037 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92260	15.7742	1015
92256	0.9222	231
92259	0.1934	71
92258	0.1787	108
92250	0.1246	59
92255	0.1131	70
92252	0.1044	55
92251	0.0431	29
92254	0.0409	17
92257	0.0365	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	96.85	gold quality
parietal pleura	UBERON:0002400	96.59	gold quality
mucosa of stomach	UBERON:0001199	96.30	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.53	gold quality
mammary duct	UBERON:0001765	95.42	gold quality
upper arm skin	UBERON:0004263	95.07	gold quality
epithelium of mammary gland	UBERON:0003244	94.88	gold quality
sural nerve	UBERON:0015488	94.30	gold quality
pleura	UBERON:0000977	93.81	gold quality
orbitofrontal cortex	UBERON:0004167	93.68	gold quality
frontal pole	UBERON:0002795	93.48	gold quality
periodontal ligament	UBERON:0008266	92.57	gold quality
mucosa of urinary bladder	UBERON:0001259	91.55	gold quality
skin of abdomen	UBERON:0001416	91.49	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.39	gold quality
gall bladder	UBERON:0002110	91.37	gold quality
penis	UBERON:0000989	91.03	gold quality
zone of skin	UBERON:0000014	90.93	gold quality
endothelial cell	CL:0000115	90.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.17	gold quality
skin of leg	UBERON:0001511	90.11	gold quality
blood vessel layer	UBERON:0004797	90.04	gold quality
hair follicle	UBERON:0002073	89.98	gold quality
superior frontal gyrus	UBERON:0002661	89.69	gold quality
nipple	UBERON:0002030	89.56	gold quality
cervix squamous epithelium	UBERON:0006922	89.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.50	gold quality
CA1 field of hippocampus	UBERON:0003881	89.41	gold quality
mammalian vulva	UBERON:0000997	88.91	gold quality
visceral pleura	UBERON:0002401	88.46	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	891.56
E-ANND-3	yes	8.11
E-GEOD-81608	yes	7.29
E-ENAD-27	no	3.35

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

34 targets.

Target	Regulation
ARC	Activation
BCL2L1	Unknown
BDNF
BDNF-AS
BTK
CAT	Activation
CD40LG
CD8A
CREBBP
CSF2
CYP19A1
EGR1	Repression
EGR2
FASLG	Activation
FXN	Activation
GABRA4	Unknown
GABRB3
GADD45B
GRIN1
IFNGR1
IGBP1
IL4	Activation
JUN
NAB2	Activation
NGF
NGFR
NOTCH1
NTRK1
PRL	Activation
SPRY1	Unknown

JASPAR motifs

Motif	Name	Family
MA0732.1	EGR3	Three-zinc finger Kruppel-related
MA0732.2	EGR3	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:7891721

Upstream regulators (CollecTRI, top): CREB1, EGR2, MYC, NAB2, NFATC1, NFATC2, NRG1, SRF, SSRP1, TXK

miRNA regulators (miRDB)

164 targeting EGR3, 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-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter (PMID:11909874)
• Vascularendothelial growth factor induces expression of NR4A nuclear receptors and Egr3 via KDR and KDR-mediated signaling mechanisms. (PMID:14525795)
• data suggest that Egr3 is a target for the estrogen receptor alpha (PMID:15171706)
• Egr-2 and Egr-3 transcription is enhanced by Hepatitis B virus X protein, which induces fasL gene expression (PMID:15173177)
• These findings support the previous genetic association of altered calcineurin signaling with schizophrenia pathogenesis and identify EGR3 as a compelling susceptibility gene. (PMID:17360599)
• findings indicate that Egr3 has an essential downstream role in VEGF-mediated endothelial functions leading to angiogenesis and may have particular relevance for adult angiogenic processes involved in vascular repair and neovascular disease (PMID:18059339)
• Enforced expression of Egr3 transgene, from the CD2 antigen promoter, facilitates development of RAG2-deficient double-negative (DN) stage 3 thymocytes to the DN4 stage and subsequently to the double-positive stage of development. (PMID:19124717)
• Data show that VEGFR1 promoter binding sites for ELF-1, CREB and EGR-1/3 play a positive role in gene transcription in endothelial cells. (PMID:19822898)
• Egr-3 is a critical determinant of VEGF signaling in activated endothelial cells (PMID:19965691)
• Results suggest that in many cells of neuroectodermal and epithelial origin EGR1, EGR2, and EGR3 activate NAB2 transcription which is in turn repressed by NAB2, thus establishing a negative feedback loop. (PMID:20506119)
• This study demoistrated that ERG3 are not genetic risk factors for schizophrenia in japanese. (PMID:20537399)
• SNP rs35201266 in intron 1 of the EGR3 gene showed a significant association with schizophrenia (PMID:20687139)
• EGR3 bound to the TREM-1 promoter. (PMID:21421043)
• Study supports the association of EGR3 with schizophrenia in Han Chinese sample. (PMID:22276163)
• EGR3, a gene that translates environmental stimuli into long-term changes in the brain, may be associated with risk for child bipolar disorder 1. (PMID:22370066)
• EGR3 gene may play an important role in schizophrenia susceptibility (PMID:22425949)
• Egr3 mRNA expression reveals that Egr3 mRNA expression is increased in tumor cells of non-relapsed samples compared to normal prostate cells, but is significantly lower in relapsed samples compared to non-relapse. (PMID:23342084)
• Decreased EGR3 expression might play a critical role in the differentiation, proliferation, metastasis and progression of gastric cancer cells. (PMID:23460371)
• EGR2 and EGR3 are regulated by NFkappaB and MAPK signalling pathways downstream of TNFalpha stimulation in breast adipose fibroblasts, and this in turn is upstream of CYP19A1 transcription via PI.4 (PMID:23485457)
• Our results suggest that Egr-3 is a transcription factor associated with TGF-beta1 expression and in vivo regulatory activity (PMID:23904169)
• These results provide the first evidence that Egr-3, is up-regulated in scleroderma and is necessary and sufficient for profibrotic responses. (PMID:23906810)
• These data suggest that type I IFN stimulation induces a rapid recruitment of a repressive Egr3/Nab1 complex that silences transcription from the ifngr1 promoter. (PMID:23935197)
• Genetic variation in EGR3 may affect prefrontal function through neurodevelopment (PMID:23962955)
• Data shows association of Egr3 genetic polymorphisms and coronary artery disease in the Uygur and Han of China (PMID:24886494)
• EGR3 promotes excessive production of IL6 and IL8 observed during the progression of prostate cancer. (PMID:25633035)
• These findings support previously reported associations between EGR3 and schizophrenia. (PMID:26474411)
• In the PPI network, genes may be involved in Down syndrome (DS) by interacting with others, including nuclear receptor subfamily 4 group A member 2 (NR4A2)early growth response (EGR)2 and NR4A2EGR3. Therefore, RUNX1, NR4A2, EGR2, EGR3 and ID4 may be key genes associated with the pathogenesis of DS. (PMID:27667480)
• Egr2 and Egr3 have emerged as regulatory molecules that suppress excessive immune responses. Mice deficient for Egr2 and Egr3 develop a lupus-like disease with dysregulated activation of effector T cells. Egr2 and Egr3 confer suppressive activity to CD4(+) T cells and regulate the production of inhibitory cytokines such as IL-10 and TGF-beta1. (PMID:27856665)
• miR-718 acts as a tumor suppressive microRNA in hepatocellular carcinoma via regulating the expression of EGR3, which may provide a new diagnostic marker and treatment target for HCC (PMID:28070994)
• EGR3 contributes to cell growth inhibition via upregulation of FasL in Hepatocellular carcinoma. (PMID:28098878)
• KSRP decreased EGR3 mRNA stability in an ARE-independent manner. (PMID:28847731)
• Study demonstrated that EGR3 expression was enhanced in prostate cancer (PC) tissues. EGR3 was proposed as a possible target of miR335, and was negatively regulated by miR335. Silencing EGR3 suppressed the viability and angiogenesis of PC cell line. (PMID:31081063)
• Silencing of miRNA-210 inhibits the progression of liver cancer and Hepatitis B virus-associated liver cancer via up-regulating EGR3. (PMID:32138690)
• Expression and prognostic value of the transcription factors EGR1 and EGR3 in gliomas. (PMID:32518380)
• Schizophrenia risk candidate EGR3 is a novel transcriptional regulator of RELN and regulates neurite outgrowth via the Reelin signal pathway in vitro. (PMID:33113163)
• HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia. (PMID:33485349)
• XIST promotes apoptosis and the inflammatory response in CSE-stimulated cells via the miR-200c-3p/EGR3 axis. (PMID:34243729)
• Egr2 and 3 maintain anti-tumour responses of exhausted tumour infiltrating CD8 + T cells. (PMID:36342511)
• The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome. (PMID:37100882)
• EGR3 and estrone are involved in the tamoxifen resistance and progression of breast cancer. (PMID:37999751)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	egr3	ENSDARG00000089156
mus_musculus	Egr3	ENSMUSG00000033730
rattus_norvegicus	Egr3	ENSRNOG00000017828

Paralogs (4): EGR1 (ENSG00000120738), EGR2 (ENSG00000122877), EGR4 (ENSG00000135625), WT1 (ENSG00000184937)

Protein

Protein identifiers

Early growth response protein 3 — Q06889 (reviewed: Q06889)

Alternative names: Zinc finger protein pilot

All UniProt accessions (2): Q06889, E5RIM5

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcription factor involved in muscle spindle development.

Subcellular location. Nucleus.

Similarity. Belongs to the EGR C2H2-type zinc-finger protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q06889-1	1	yes
Q06889-2	2

RefSeq proteins (2): NP_001186809, NP_004421* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR021849	EGR_N	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF11928

UniProt features (12 total): zinc finger region 3, compositionally biased region 3, sequence conflict 2, region of interest 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06889-F1	50.90	0.14

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription

MSigDB gene sets: 525 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CIRCADIAN_RHYTHM, AHRARNT_01, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, LEE_SP4_THYMOCYTE, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CELL_CHEMOTAXIS, DORN_ADENOVIRUS_INFECTION_12HR_UP, BECKER_TAMOXIFEN_RESISTANCE_UP, CMYB_01

GO Biological Process (15): positive regulation of endothelial cell proliferation (GO:0001938), cell migration involved in sprouting angiogenesis (GO:0002042), regulation of transcription by RNA polymerase II (GO:0006357), neuromuscular synaptic transmission (GO:0007274), peripheral nervous system development (GO:0007422), muscle organ development (GO:0007517), circadian rhythm (GO:0007623), positive regulation of T cell differentiation in thymus (GO:0033089), endothelial cell chemotaxis (GO:0035767), cellular response to vascular endothelial growth factor stimulus (GO:0035924), negative regulation of apoptotic process (GO:0043066), cellular response to fibroblast growth factor stimulus (GO:0044344), regulation of gamma-delta T cell differentiation (GO:0045586), positive regulation of transcription by RNA polymerase II (GO:0045944), system development (GO:0048731)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), synapse (GO:0045202), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cellular response to growth factor stimulus	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
chemical synaptic transmission	1
nervous system development	1
system development	1
animal organ development	1
muscle structure development	1
rhythmic process	1
T cell differentiation in thymus	1
regulation of T cell differentiation in thymus	1
positive regulation of T cell differentiation	1
endothelial cell migration	1
cell chemotaxis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to fibroblast growth factor	1
gamma-delta T cell differentiation	1
regulation of T cell differentiation	1
regulation of gamma-delta T cell activation	1
positive regulation of DNA-templated transcription	1
multicellular organism development	1
anatomical structure development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1

Protein interactions and networks

STRING

1824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EGR3	NAB1	Q13506	950
EGR3	NAB2	Q15742	917
EGR3	FOSB	P53539	845
EGR3	FOS	P01100	821
EGR3	NR4A1	P22736	752
EGR3	GABRA4	P48169	701
EGR3	ATF3	P18847	640
EGR3	PRX	Q9BXM0	584
EGR3	NFATC3	Q12968	552
EGR3	NR4A2	P43354	527
EGR3	IL2	P01585	526
EGR3	DUSP6	Q16828	524
EGR3	SMAD3	P84022	521
EGR3	BTG2	P78543	513
EGR3	SOX10	P56693	503

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
BRCA1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
	JUN	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (2): HIST1H2BD (Cross-Linking-MS (XL-MS)), EGR3 (Two-hybrid)

ESM2 similar proteins: A1XSY8, O08656, O43474, P08046, P08151, P08152, P08154, P09022, P09027, P10070, P11161, P13360, P15976, P17679, P18146, P19544, P22561, P26632, P26633, P31249, P40656, P43300, P43301, P43429, P46153, P47806, P49639, P49952, P50476, P51774, Q05159, Q06889, Q07424, Q08427, Q0VGT2, Q29W20, Q60793, Q61169, Q6NW96, Q6P0J3

Diamond homologs: A1XSY8, A4II20, O73691, O73692, O73693, O73694, P08046, P08152, P08154, P11161, P18146, P26632, P26633, P26634, P26635, P31509, P43300, P43301, P51774, P80944, Q00453, Q00911, Q05159, Q05215, Q06889, Q08427, Q12132, Q18250, Q29419, Q29W20, Q6GQH4, Q6NTY6, Q9GL32, Q9WUF2, A1C6L9, A1DH89, A2QCJ9, B0XSK6, B8NGC8, O14335

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
EGR3	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
EGR3	“down-regulates quantity by repression”	NAB2	“transcriptional regulation”
NAB2	“down-regulates quantity by repression”	EGR3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

338 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22692787:TTA:T	donor_loss	1.0000
8:22692788:TA:T	donor_loss	1.0000
8:22692789:A:C	donor_loss	1.0000
8:22692790:C:G	donor_loss	1.0000
8:22691479:TTCT:T	acceptor_gain	0.9900
8:22691480:TCT:T	acceptor_gain	0.9900
8:22691481:CT:C	acceptor_gain	0.9900
8:22691481:CTC:C	acceptor_gain	0.9900
8:22691482:TCT:T	acceptor_gain	0.9900
8:22691483:C:CC	acceptor_gain	0.9900
8:22691493:C:CT	acceptor_gain	0.9900
8:22691494:G:T	acceptor_gain	0.9900
8:22692789:A:AC	donor_gain	0.9900
8:22692790:C:CC	donor_gain	0.9900
8:22691479:TTCTC:T	acceptor_loss	0.9800
8:22691480:TCTC:T	acceptor_loss	0.9800
8:22691482:TC:T	acceptor_loss	0.9800
8:22691483:C:T	acceptor_loss	0.9800
8:22691484:T:A	acceptor_loss	0.9800
8:22691478:ATTCT:A	acceptor_gain	0.9700
8:22691483:C:G	acceptor_gain	0.9700
8:22692278:C:A	donor_gain	0.9500
8:22692815:C:CT	donor_gain	0.9400
8:22692816:T:TT	donor_gain	0.9400
8:22691784:T:TA	donor_gain	0.9300
8:22692814:A:AC	donor_gain	0.9300
8:22692277:C:CA	donor_gain	0.9200
8:22692786:CTTA:C	donor_gain	0.9200
8:22691486:C:CT	acceptor_gain	0.9100
8:22692785:CCTTA:C	donor_gain	0.9100

AlphaMissense

2566 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22690611:A:C	F342L	1.000
8:22690611:A:T	F342L	1.000
8:22690613:A:G	F342L	1.000
8:22690625:A:G	C338R	1.000
8:22690634:A:G	C335R	1.000
8:22690668:G:C	H323Q	1.000
8:22690668:G:T	H323Q	1.000
8:22690670:G:C	H323D	1.000
8:22690678:A:G	L320P	1.000
8:22690695:G:C	F314L	1.000
8:22690695:G:T	F314L	1.000
8:22690696:A:G	F314S	1.000
8:22690697:A:G	F314L	1.000
8:22690707:G:C	C310W	1.000
8:22690708:C:T	C310Y	1.000
8:22690709:A:G	C310R	1.000
8:22690716:G:C	C307W	1.000
8:22690718:A:G	C307R	1.000
8:22690750:A:G	L296P	1.000
8:22690779:G:C	F286L	1.000
8:22690779:G:T	F286L	1.000
8:22690780:A:G	F286S	1.000
8:22690781:A:G	F286L	1.000
8:22690612:A:G	F342S	0.999
8:22690619:G:T	R340S	0.999
8:22690623:G:C	C338W	0.999
8:22690624:C:G	C338S	0.999
8:22690624:C:T	C338Y	0.999
8:22690625:A:T	C338S	0.999
8:22690632:G:C	C335W	0.999

dbSNP variants (sampled 300 via entrez): RS1000336113 (8:22690439 G>A), RS1000451981 (8:22690289 C>T), RS1000672938 (8:22692112 G>A,C), RS1000787092 (8:22691910 C>G,T), RS1000846963 (8:22695009 G>A), RS1001054016 (8:22688171 A>C,G), RS1001324623 (8:22687252 C>T), RS1001410654 (8:22687816 T>A,C), RS1001780790 (8:22694259 G>T), RS1001789251 (8:22694595 C>T), RS1001904190 (8:22692556 C>T), RS1002281947 (8:22688607 C>A), RS1002610415 (8:22688096 A>G), RS1003688823 (8:22690137 C>A,T), RS1003692482 (8:22687728 T>C)

Disease associations

OMIM: gene MIM:602419 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006291_11	Spherical equivalent or myopia (age of diagnosis)	2.000000e-08
GCST010002_271	Refractive error	2.000000e-17
GCST90014268_20	Cataracts	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases expression, increases reaction, affects cotreatment, decreases expression	14
Valproic Acid	increases expression, affects expression, decreases expression	6
bisphenol A	increases expression	3
arsenite	increases expression, decreases reaction, decreases expression, increases abundance, affects expression	3
Silicon Dioxide	increases expression	3
methylmercuric chloride	increases expression	2
trichostatin A	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Fulvestrant	decreases expression, decreases reaction, increases expression	2
Arsenic	decreases reaction, increases expression, decreases expression, increases abundance	2
Benzene	increases expression	2
Cadmium	decreases expression, increases abundance, decreases reaction, increases expression	2
Diethylstilbestrol	increases expression	2
Estrone	increases expression	2
Formaldehyde	increases expression	2
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Genistein	increases expression	2
Raloxifene Hydrochloride	decreases reaction, increases expression, decreases expression	2
perfluoropentanoic acid	decreases reaction, increases expression	1
urushiol	increases expression	1
ethylbenzene	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
beta-lapachone	increases expression	1
afimoxifene	decreases reaction, increases expression	1
sodium arsenite	decreases expression, increases abundance	1
pyrrolidine dithiocarbamic acid	affects cotreatment, increases expression	1
nonylphenol	increases expression	1

Clinical trials (associated diseases)

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