IRX3

Summary

IRX3 (iroquois homeobox 3, HGNC:14360) is a protein-coding gene on chromosome 16q12.2, encoding Iroquois-class homeodomain protein IRX-3 (P78415). Transcription factor involved in SHH-dependent neural patterning.

IRX3 is a member of the Iroquois homeobox gene family (see IRX1; MIM 606197) and plays a role in an early step of neural development (Bellefroid et al., 1998 [PubMed 9427753]). Members of this family appear to play multiple roles during pattern formation of vertebrate embryos (Lewis et al., 1999 [PubMed 10370142]).

Source: NCBI Gene 79191 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_024336

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14360
Approved symbol	IRX3
Name	iroquois homeobox 3
Location	16q12.2
Locus type	gene with protein product
Status	Approved
Aliases	IRX-1
Ensembl gene	ENSG00000177508
Ensembl biotype	protein_coding
OMIM	612985
Entrez	79191

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000329734, ENST00000558054, ENST00000558180

RefSeq mRNA: 1 — MANE Select: NM_024336 NM_024336

CCDS: CCDS10750

Canonical transcript exons

ENST00000329734 — 4 exons

Exon	Start	End
ENSE00001318461	54285784	54286787
ENSE00001388671	54284497	54285613
ENSE00001722620	54283304	54283740
ENSE00003484314	54284246	54284312

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4718 / max 152.9016, expressed in 1118 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157420	3.5275	992
157418	2.0024	602
157411	0.5306	285
157417	0.4111	263

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	99.37	gold quality
penis	UBERON:0000989	99.02	gold quality
upper arm skin	UBERON:0004263	99.00	gold quality
left ventricle myocardium	UBERON:0006566	99.00	gold quality
bronchial epithelial cell	CL:0002328	98.74	gold quality
bronchus	UBERON:0002185	98.65	gold quality
mammalian vulva	UBERON:0000997	98.40	gold quality
epithelium of mammary gland	UBERON:0003244	98.26	gold quality
mammary duct	UBERON:0001765	98.25	gold quality
trachea	UBERON:0003126	98.11	gold quality
gingival epithelium	UBERON:0001949	97.86	gold quality
renal medulla	UBERON:0000362	97.63	gold quality
heart right ventricle	UBERON:0002080	97.63	gold quality
upper leg skin	UBERON:0004262	97.47	gold quality
urethra	UBERON:0000057	97.41	gold quality
skin of abdomen	UBERON:0001416	97.40	gold quality
parotid gland	UBERON:0001831	96.60	gold quality
skin of hip	UBERON:0001554	96.59	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.51	gold quality
zone of skin	UBERON:0000014	96.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.34	gold quality
epithelium of nasopharynx	UBERON:0001951	96.06	gold quality
gingiva	UBERON:0001828	95.93	gold quality
myocardium	UBERON:0002349	95.86	silver quality
skin of leg	UBERON:0001511	95.71	gold quality
germinal epithelium of ovary	UBERON:0001304	95.70	gold quality
pharyngeal mucosa	UBERON:0000355	95.43	gold quality
mammary gland	UBERON:0001911	94.69	gold quality
saliva-secreting gland	UBERON:0001044	94.66	gold quality
nasal cavity mucosa	UBERON:0001826	94.63	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	438.39
E-ANND-3	yes	22.34
E-MTAB-6701	yes	18.24
E-MTAB-9388	yes	12.34
E-MTAB-6678	yes	10.17
E-CURD-114	no	19.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
GJA1	Repression
GJA5	Activation
KCND2

Upstream regulators (CollecTRI, top): PAX6

miRNA regulators (miRDB)

48 targeting IRX3, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1284	99.67	73.56	1353

Literature-anchored findings (GeneRIF, showing 24)

• IRX3 function may have a direct functional relationship to both obesity and type 2 diabetes. (PMID:20080751)
• data suggest that IRX3 is a functional long-range target of obesity-associated variants within FTO and represents a novel determinant of body mass and composition (PMID:24646999)
• Strategies to pharmacologically regulate Irx3 function in adult endothelial cells may provide new therapies for angiogenesis. (PMID:25512384)
• Genome editing in primary preadipocytes to create the obesity risk allele of rs1421085 caused increased expression of IRX3 and IRX5 during early adipocyte differentiation by disrupting a binding site for the ARID5B repressor. (PMID:26287746)
• Primary preadipocytes from carriers of the obesity risk allele rs1421085, in which expression of IRX3 and IRX5 is increased, displayed excessive accumulation of triglycerides, reduced mitochondrial oxidative capacity, reduced white adipocyte browning, and reduced thermogenesis relative to primary preadipocytes from nonrisk allele carriers. (PMID:26287746)
• This is the first study to reveal that genetic variants of both FTO and IRX3 genes are in high linkage disequilibrium (LD) and are associated with obesity risk in North Indians. (PMID:26440677)
• Downregulation of miR-377 may contribute to the upregulation of IRX3 in HCC. (PMID:27222047)
• the association between FTO and obesity appears to be due to its influence on expression of IRX3 [Figure 1]. Genetic studies indicated FTO as an important gene for obesity risk in various populations but the recent developments suggest that obesity-associated FTO SNPs have long-range interactions with IRX3. (PMID:27241637)
• Increased adipocyte-specific expression of IRX3 correlates with the presence of the FTO obesity risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy. (PMID:27560134)
• IRX3 genetic variants associate with birth weight, body mass index and AST/ALT-related transaminase metabolism, supporting the role of IRX3 as an obesity-associated susceptibility gene. (PMID:28316138)
• Results show that IRX3 deficiency repressed the browning program of white adipocytes partially by regulating UCP1 transcriptional activity. Rare variants of IRX3 were associated with human obesity. (PMID:28988979)
• Promotion of IRX3 signalling or inhibition of IRX5 signalling could be a route towards differentiation therapy for Wilms tumour, in which WNT5A is a candidate molecule for enforced tubular maturation. (PMID:30246301)
• Data show that hypothalamic Irx3 is down-regulated by prolonged fasting and by a high-fat diet. The hypothalamic inhibition of Irx3 results in increased body mass gain due to increased caloric intake and reduced energy expenditure accompanied by reduced BAT thermogenesis. Thus, Irx3 is abnormally regulated in diet-induced obesity, and further reducing its hypothalamic levels results in increased body mass. (PMID:30522931)
• Lifestyle modification may exert its effects on obesity through changes in the expression level of the FTO and IRX3 genes. However, FTO genotype plays a role in the extent of the effect of lifestyle changes on gene expression. (PMID:31126299)
• Irx3 is required for preadipocyte identity and differentiation capacity. (PMID:31751577)
• Hypothalamic IRX3: A New Player in the Development of Obesity. (PMID:32035736)
• Associations of nicotidamide-N-methyltransferase, FTO, and IRX3 genetic variants with body mass index and resting energy expenditure in Mexican subjects. (PMID:32651404)
• Clinical utility of irx3 in keratoconus. (PMID:32924191)
• Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults. (PMID:33232597)
• IRX3 Overexpression Enhances Ucp1 Expression In Vivo. (PMID:33776928)
• Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5. (PMID:34083488)
• The Hematopoietic TALE-Code Shows Normal Activity of IRX1 in Myeloid Progenitors and Reveals Ectopic Expression of IRX3 and IRX5 in Acute Myeloid Leukemia. (PMID:35328612)
• IRX3 plays an important role in the pathogenesis of metabolic-associated fatty liver disease by regulating hepatic lipid metabolism. (PMID:35957832)
• Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess. (PMID:36415696)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	irx3b	ENSDARG00000031138
danio_rerio	irx3a	ENSDARG00000101076
mus_musculus	Irx3	ENSMUSG00000031734
rattus_norvegicus	Irx3	ENSRNOG00000011533

Paralogs (6): IRX4 (ENSG00000113430), MKX (ENSG00000150051), IRX6 (ENSG00000159387), IRX1 (ENSG00000170549), IRX2 (ENSG00000170561), IRX5 (ENSG00000176842)

Protein

Protein identifiers

Iroquois-class homeodomain protein IRX-3 — P78415 (reviewed: P78415)

Alternative names: Homeodomain protein IRXB1, Iroquois homeobox protein 3

All UniProt accessions (2): P78415, J3QR11

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in SHH-dependent neural patterning. Together with NKX2-2 and NKX6-1 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class I proteins of neuronal progenitor factors, which are repressed by SHH signals. Involved in the transcriptional repression of MNX1 in non-motor neuron cells. Acts as a regulator of energy metabolism.

Subcellular location. Nucleus.

Similarity. Belongs to the TALE/IRO homeobox family.

RefSeq proteins (1): NP_077312* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003893	Iroquois_homeo	Domain
IPR008422	KN_HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF05920

UniProt features (11 total): compositionally biased region 3, modified residue 2, sequence variant 2, chain 1, DNA-binding region 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78415-F1	54.98	0.10

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 323, 326

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_METANEPHROS_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_LOOP_OF_HENLE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM

GO Biological Process (18): negative regulation of transcription by RNA polymerase II (GO:0000122), metanephros development (GO:0001656), Purkinje myocyte development (GO:0003165), atrioventricular bundle cell differentiation (GO:0003167), regulation of transcription by RNA polymerase II (GO:0006357), mesoderm development (GO:0007498), neuron differentiation (GO:0030182), negative regulation of neuron differentiation (GO:0045665), positive regulation of neuron differentiation (GO:0045666), positive regulation of transcription by RNA polymerase II (GO:0045944), cell development (GO:0048468), His-Purkinje system cell differentiation (GO:0060932), specification of loop of Henle identity (GO:0072086), energy homeostasis (GO:0097009), regulation of cell communication by electrical coupling involved in cardiac conduction (GO:1901844), positive regulation of gap junction assembly (GO:1903598), regulation of DNA-templated transcription (GO:0006355), proximal/distal pattern formation involved in nephron development (GO:0072047)

GO Molecular Function (6): 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), axon (GO:0030424)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
His-Purkinje system development	2
cell differentiation	2
neuron differentiation	2
regulation of neuron differentiation	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
kidney development	1
ventricular cardiac muscle tissue development	1
bundle of His development	1
His-Purkinje system cell differentiation	1
regulation of DNA-templated transcription	1
tissue development	1
generation of neurons	1
negative regulation of cell differentiation	1
positive regulation of cell differentiation	1
positive regulation of DNA-templated transcription	1
anatomical structure development	1
cellular developmental process	1
cardiac muscle cell differentiation	1
loop of Henle development	1
specification of nephron tubule identity	1
multicellular organismal-level homeostasis	1
regulation of cell communication by electrical coupling	1
cell communication by electrical coupling involved in cardiac conduction	1
gap junction assembly	1
positive regulation of cell junction assembly	1
regulation of gap junction assembly	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
proximal/distal pattern formation	1
nephron development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1

Protein interactions and networks

STRING

1732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IRX3	FTO	Q9C0B1	811
IRX3	NKX2-2	O95096	748
IRX3	AKAP11	Q9UKA4	731
IRX3	OLIG2	Q13516	727
IRX3	SIX3	O95343	696
IRX3	RPGRIP1L	Q68CZ1	671
IRX3	DBX2	Q6ZNG2	644
IRX3	IRX5	P78411	634
IRX3	PAX6	P26367	625
IRX3	ARID5B	Q14865	606
IRX3	NKX6-1	P78426	594
IRX3	DBX1	A6NMT0	580
IRX3	NKX6-2	Q9C056	566
IRX3	GBX2	P52951	553
IRX3	GPC5	P78333	551
IRX3	SMYD1	Q8NB12	551

IntAct

2 interactions, top by confidence:

A	B	Type	Score
HSCB	IRX3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): IRX3 (Affinity Capture-RNA), IRX3 (Negative Genetic), IRX3 (Proximity Label-MS)

ESM2 similar proteins: A2A9A2, A6QQ94, A6YP92, A7MB54, B5RHS5, E9PZZ1, M0R6D8, O02786, O08934, O09029, O35085, P13297, P28360, P46153, P50548, P78413, P78414, P78415, P81067, P81068, P84550, P97830, Q12952, Q13207, Q14549, Q14774, Q2VL76, Q2VL77, Q2VL78, Q2VL79, Q2VL80, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86, Q2VL87, Q2VL88, Q2VWA4, Q5SQQ9

Diamond homologs: A1YGI6, A6NDR6, A8K0S8, A8WL06, B7ZRT8, O00470, O04136, O14770, O22300, O42261, O46339, O65685, O70477, P41779, P41817, P46606, P48000, P48001, P48002, P48731, P53147, P54269, P55347, P56659, P56660, P56664, P56665, P56669, P70284, P78412, P78413, P78414, P78415, P79937, P81067, P81068, P97367, P97368, Q0E3C3, Q0J6N4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IRX3	“down-regulates quantity by repression”	GJA1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

414 predictions. Top by Δscore:

Variant	Effect	Δscore
16:54285778:TCTTA:T	donor_loss	1.0000
16:54285779:CTTAC:C	donor_loss	1.0000
16:54285780:TTACC:T	donor_loss	1.0000
16:54285781:TA:T	donor_loss	1.0000
16:54285783:CCAG:C	donor_gain	1.0000
16:54284244:ACCG:A	donor_gain	0.9900
16:54284245:CCGC:C	donor_gain	0.9900
16:54284323:C:CT	acceptor_gain	0.9900
16:54284324:G:T	acceptor_gain	0.9900
16:54285612:CC:C	acceptor_gain	0.9900
16:54285613:CC:C	acceptor_gain	0.9900
16:54285613:CCTG:C	acceptor_loss	0.9900
16:54285614:CTGT:C	acceptor_loss	0.9900
16:54285615:T:G	acceptor_loss	0.9900
16:54285623:CA:C	acceptor_gain	0.9900
16:54285624:A:C	acceptor_gain	0.9900
16:54285782:A:AC	donor_gain	0.9900
16:54285783:C:CC	donor_gain	0.9900
16:54284312:TC:T	acceptor_loss	0.9800
16:54284313:C:CA	acceptor_loss	0.9800
16:54284314:T:G	acceptor_loss	0.9800
16:54285610:CGCC:C	acceptor_gain	0.9800
16:54285611:GCC:G	acceptor_gain	0.9800
16:54285612:CCC:C	acceptor_gain	0.9800
16:54285619:C:CT	acceptor_gain	0.9800
16:54285782:ACCAG:A	donor_gain	0.9800
16:54285783:CCAGC:C	donor_gain	0.9800
16:54284313:C:CC	acceptor_gain	0.9700
16:54285614:C:CC	acceptor_gain	0.9700
16:54284309:CGAT:C	acceptor_gain	0.9600

AlphaMissense

3176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:54284826:A:T	L352H	1.000
16:54284831:C:A	W350C	1.000
16:54284831:C:G	W350C	1.000
16:54284833:A:G	W350R	1.000
16:54284833:A:T	W350R	1.000
16:54284835:A:C	I349S	1.000
16:54284835:A:G	I349T	1.000
16:54284835:A:T	I349N	1.000
16:54285302:C:A	W193C	1.000
16:54285302:C:G	W193C	1.000
16:54285304:A:G	W193R	1.000
16:54285304:A:T	W193R	1.000
16:54285311:C:A	K190N	1.000
16:54285311:C:G	K190N	1.000
16:54285313:T:C	K190E	1.000
16:54285320:C:A	K187N	1.000
16:54285320:C:G	K187N	1.000
16:54285322:T:C	K187E	1.000
16:54285323:C:A	K186N	1.000
16:54285323:C:G	K186N	1.000
16:54285324:T:A	K186M	1.000
16:54285325:T:C	K186E	1.000
16:54285327:A:G	L185P	1.000
16:54285327:A:T	L185H	1.000
16:54285328:G:A	L185F	1.000
16:54285330:C:G	R184P	1.000
16:54285331:G:A	R184C	1.000
16:54285331:G:C	R184G	1.000
16:54285331:G:T	R184S	1.000
16:54285333:C:G	R183P	1.000

dbSNP variants (sampled 300 via entrez): RS1000287103 (16:54288660 G>A), RS1000658902 (16:54288385 G>T), RS1000679908 (16:54284053 C>T), RS1002352592 (16:54285436 G>A), RS1002416632 (16:54285687 C>A,G,T), RS1002751952 (16:54287187 C>T), RS1004431585 (16:54288303 A>T), RS1006888793 (16:54286446 G>A,C), RS1006921635 (16:54286678 C>T), RS1007217812 (16:54287510 G>A), RS1008889233 (16:54288688 G>A), RS1009066150 (16:54283060 G>T), RS1009425441 (16:54284543 A>G), RS1011067164 (16:54285713 G>A,C,T), RS1011432212 (16:54287427 G>A,T)

Disease associations

OMIM: gene MIM:612985 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001066_13	Dialysis-related mortality	9.000000e-06
GCST005950_1	Body mass index x sex x age interaction (4df test)	2.000000e-187
GCST005951_192	Body mass index	4.000000e-188
GCST005952_1	Body mass index (age>50)	1.000000e-97
GCST007239_23	Ovarian cancer	8.000000e-07
GCST007324_126	Adventurousness	3.000000e-08
GCST007325_113	General risk tolerance (MTAG)	3.000000e-10
GCST008395_11	End-stage kidney disease	8.000000e-07
GCST008595_206	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-08
GCST010151_23	Carotid intima media thickness x smoking interaction	4.000000e-06
GCST011796_15	Lung function (FVC) in asthma	3.000000e-08
GCST90011899_27	Aspartate aminotransferase levels	2.000000e-36
GCST90086158_17	Brugada syndrome	1.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008579	risk-taking behaviour
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0006527	smoking status measurement
EFO:0004312	vital capacity
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation, affects cotreatment, increases expression	7
Tretinoin	increases expression, affects expression, decreases expression	4
trichostatin A	affects cotreatment, increases expression	3
Smoke	decreases expression, increases abundance, increases expression	3
Tetrachlorodibenzodioxin	decreases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
cupric chloride	decreases expression	1
avobenzone	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Zoledronic Acid	decreases expression	1
Arsenic	increases methylation	1

Clinical trials (associated diseases)

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