ARHGEF3

Summary

ARHGEF3 (Rho guanine nucleotide exchange factor 3, HGNC:683) is a protein-coding gene on chromosome 3p14.3, encoding Rho guanine nucleotide exchange factor 3 (Q9NR81). Acts as a guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.

Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 50650 — RefSeq curated summary.

At a glance

• GWAS associations: 62
• Clinical variants (ClinVar): 110 total
• MANE Select transcript: NM_019555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:683
Approved symbol	ARHGEF3
Name	Rho guanine nucleotide exchange factor 3
Location	3p14.3
Locus type	gene with protein product
Status	Approved
Aliases	STA3, XPLN, GEF3, DKFZP434F2429
Ensembl gene	ENSG00000163947
Ensembl biotype	protein_coding
OMIM	612115
Entrez	50650

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000296315, ENST00000338458, ENST00000413728, ENST00000465659, ENST00000468466, ENST00000468727, ENST00000473779, ENST00000477440, ENST00000477833, ENST00000481422, ENST00000486829, ENST00000495373, ENST00000496106, ENST00000497267, ENST00000498517, ENST00000863032, ENST00000863033, ENST00000863034

RefSeq mRNA: 13 — MANE Select: NM_019555 NM_001128615, NM_001128616, NM_001289698, NM_001377407, NM_001377408, NM_001377409, NM_001377410, NM_001377411, NM_001377412, NM_001377413, NM_001377414, NM_001377415, NM_019555

CCDS: CCDS2878, CCDS46854, CCDS46855, CCDS74948, CCDS93293

Canonical transcript exons

ENST00000296315 — 10 exons

Exon	Start	End
ENSE00001079951	56751056	56751132
ENSE00003495357	56737185	56737355
ENSE00003521276	56754981	56755151
ENSE00003524676	56745205	56745462
ENSE00003579181	56732238	56732424
ENSE00003596462	56801703	56801949
ENSE00003662926	56753504	56753566
ENSE00003788180	56773709	56773816
ENSE00003789685	56751300	56751396
ENSE00003902679	56727420	56729622

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8176 / max 468.2735, expressed in 1683 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42628	15.4657	1435
42627	4.0828	905
42633	2.3285	314
42638	1.2039	636
42621	0.9166	269
42639	0.8330	528
42636	0.3771	167
42626	0.1376	57
42637	0.1297	52
42624	0.1045	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal glomerulus	UBERON:0000074	98.17	gold quality
metanephric glomerulus	UBERON:0004736	97.90	gold quality
endothelial cell	CL:0000115	96.67	gold quality
choroid plexus epithelium	UBERON:0003911	96.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.03	gold quality
germinal epithelium of ovary	UBERON:0001304	94.97	gold quality
middle temporal gyrus	UBERON:0002771	94.08	gold quality
granulocyte	CL:0000094	93.55	gold quality
metanephros	UBERON:0000081	93.20	gold quality
kidney epithelium	UBERON:0004819	92.84	gold quality
oral cavity	UBERON:0000167	92.47	gold quality
parietal pleura	UBERON:0002400	92.27	gold quality
cranial nerve II	UBERON:0000941	92.18	gold quality
islet of Langerhans	UBERON:0000006	91.97	gold quality
cerebellar vermis	UBERON:0004720	91.63	gold quality
pericardium	UBERON:0002407	91.49	gold quality
gingival epithelium	UBERON:0001949	91.46	gold quality
vena cava	UBERON:0004087	91.46	gold quality
adrenal cortex	UBERON:0001235	91.44	gold quality
leukocyte	CL:0000738	91.36	gold quality
adrenal gland	UBERON:0002369	91.36	gold quality
gingiva	UBERON:0001828	91.34	gold quality
left adrenal gland	UBERON:0001234	91.30	gold quality
left adrenal gland cortex	UBERON:0035825	91.17	gold quality
superior frontal gyrus	UBERON:0002661	91.13	gold quality
right adrenal gland cortex	UBERON:0035827	91.13	gold quality
right adrenal gland	UBERON:0001233	91.09	gold quality
mononuclear cell	CL:0000842	90.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.91	gold quality
palpebral conjunctiva	UBERON:0001812	90.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	29.45
E-HCAD-10	yes	19.58
E-MTAB-6058	no	30.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting ARHGEF3, 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-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
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-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1236-3P	99.94	68.04	1695

Literature-anchored findings (GeneRIF, showing 14)

• a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC (PMID:12221096)
• genetic variation in ARHGEF3 plays a role in the determination of bone density in Caucasian women. This data implicates the RhoGTPase-RhoGEF pathway in osteoporosis. (PMID:18499081)
• the association between rs7646054 in ARHGEF3 and bone mineral density observed in Caucasians was not replicated in the chinese samples. (PMID:19727905)
• XPLN is an endogenous inhibitor of mTORC2. (PMID:24043828)
• ARHGEF3 and RHOA are potential regulators of a number of genes in bone cells, with influences on ACTA2 evident in both osteoblast-like and osteoclast-like cells. (PMID:24840563)
• ARHGEF3 has a crucial role in myeloid differentiation. (PMID:25494542)
• Our findings suggest that increased expression of ARHGEF3 plays a critical oncogenic role in nasopharyngeal carcinoma pathogenesis (PMID:27028992)
• This is the first study describing the involvement of XPLN in the regulation of the mTORC2-SPARC axis, and these findings may help uncover regulatory mechanisms mediated by XPLN in idiopathic pulmonary fibrosis (PMID:28315487)
• Data suggest that modulation of ARHGEF3 gene expression in humans with a promoter-localized SNP plays a role in human megakaryocytes and human platelet function-a finding resulting from the biological follow-up of human genetic studies. Arhgef3 KO mice partially recapitulate the human phenotype. (PMID:28542600)
• The predicted expression of the ARHGEF3 gene in fibroblasts (effect, -0.48; P = 9.8 x 10-04) was associated with Major Depression. (PMID:29998287)
• Genetic variants in RET, ARHGEF3 and CTNNAL1, and relevant interaction networks, contribute to the risk of Hirschsprung disease. (PMID:32139661)
• Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins. (PMID:34267198)
• ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma. (PMID:34350290)
• ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer. (PMID:36241648)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgef3	ENSDARG00000013834
mus_musculus	Arhgef3	ENSMUSG00000021895
rattus_norvegicus	Arhgef3	ENSRNOG00000014363
drosophila_melanogaster	cyst	FBGN0032796
caenorhabditis_elegans	prhg-1	WBGENE00022391

Paralogs (8): PLEKHG6 (ENSG00000008323), ARHGEF1 (ENSG00000076928), ARHGEF18 (ENSG00000104880), ARHGEF2 (ENSG00000116584), ARHGEF11 (ENSG00000132694), NET1 (ENSG00000173848), ARHGEF12 (ENSG00000196914), ARHGEF28 (ENSG00000214944)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 3 — Q9NR81 (reviewed: Q9NR81)

Alternative names: Exchange factor found in platelets and leukemic and neuronal tissues

All UniProt accessions (10): C9J586, C9J5K8, C9J609, C9JNF2, E7EU49, E9PG37, Q9NR81, F8WC29, F8WDB7, H7C4P0

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.

Subunit / interactions. Interacts with RHOA and RHOB.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed. Highest levels are found in adult brain and skeletal muscle. Lower levels are found in heart and kidney.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NR81-1	1	yes
Q9NR81-2	2
Q9NR81-3	3
Q9NR81-4	4

RefSeq proteins (13): NP_001122087, NP_001122088, NP_001276627, NP_001364336, NP_001364337, NP_001364338, NP_001364339, NP_001364340, NP_001364341, NP_001364342, NP_001364343, NP_001364344, NP_062455* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR044129	PH_RhoGEF3_XPLN	Domain
IPR051480	Endocytic_GEF_Adapter	Family
IPR055251	SOS1_NGEF_PH	Domain

Pfam: PF00621, PF22697

UniProt features (15 total): splice variant 4, domain 2, sequence variant 2, region of interest 2, modified residue 2, chain 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR81-F1	74.88	0.56

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): 47, 70

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 299 (showing top): GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, CACCAGC_MIR138, FOSTER_TOLERANT_MACROPHAGE_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, TGACATY_UNKNOWN, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, TTGGAGA_MIR5155P_MIR519E, BROWN_MYELOID_CELL_DEVELOPMENT_UP, GNF2_SNRK

GO Biological Process (4): Rho protein signal transduction (GO:0007266), positive regulation of Rho protein signal transduction (GO:0035025), regulation of small GTPase mediated signal transduction (GO:0051056), intracellular signal transduction (GO:0035556)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Signal Transduction	3
RHO GTPase cycle	2
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
small GTPase-mediated signal transduction	2
intracellular anatomical structure	2
cellular anatomical structure	2
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
regulation of intracellular signal transduction	1
signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
cytoplasm	1

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF3	RHOB	P01121	852
ARHGEF3	RHOC	P08134	804
ARHGEF3	RICTOR	Q6R327	788
ARHGEF3	MCF2	P10911	678
ARHGEF3	RHOA	P06749	674
ARHGEF3	FGD1	P98174	631
ARHGEF3	RHOG	P35238	628
ARHGEF3	CDC42	P21181	617
ARHGEF3	PLEK	P08567	613
ARHGEF3	ROCK1	Q13464	536
ARHGEF3	MAPKAP1	Q9BPZ7	525
ARHGEF3	DEPTOR	Q8TB45	521
ARHGEF3	MLST8	Q9BVC4	508
ARHGEF3	PLEK2	Q9NYT0	500
ARHGEF3	CFAP251	Q8TBY9	478

IntAct

39 interactions, top by confidence:

A	B	Type	Score
ARHGEF3	TRIM27	psi-mi:“MI:0915”(physical association)	0.830
TRIM27	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.830
ARHGEF3	CEP70	psi-mi:“MI:0915”(physical association)	0.780
CEP70	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.780
ARHGEF3	TRIM23	psi-mi:“MI:0915”(physical association)	0.740
TRIM23	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.740
ARHGEF3	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
DDIT4L	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.560
ARHGEF3	PICK1	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.560
PBX4	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.560
TERF1	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.560
ARHGEF3	CDC42	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ARHGEF3	CEP70	psi-mi:“MI:0915”(physical association)	0.000
ARHGEF3	HSF2BP	psi-mi:“MI:0915”(physical association)	0.000
ARHGEF3	TRIM27	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): ARHGEF3 (Two-hybrid), ARHGEF3 (Two-hybrid), CEP70 (Two-hybrid), ARHGEF3 (Affinity Capture-RNA), ARHGEF3 (Affinity Capture-RNA), ARHGEF3 (Affinity Capture-MS), ARHGEF3 (Affinity Capture-RNA), TRIM23 (Two-hybrid), TRIM27 (Two-hybrid), CEP70 (Two-hybrid), ARHGEF3 (Two-hybrid), ARHGEF3 (Two-hybrid), ARHGEF3 (Two-hybrid), ARHGEF3 (Two-hybrid), ARHGEF3 (Two-hybrid)

ESM2 similar proteins: A0A0G2JTR4, A1A4S6, A2AWA9, A4FUD6, A4II46, A6H6A9, A6QNS3, A6QQZ7, O60890, P09851, P0CAX5, P20936, P23727, P26450, P27986, P50904, Q08DP6, Q12979, Q5R372, Q5R5M3, Q5R685, Q5R6F2, Q5R8I6, Q5RCC1, Q5RCW6, Q5SSL4, Q5T2T1, Q5U2Y3, Q5ZJ17, Q5ZLX4, Q5ZMW5, Q62696, Q63787, Q6Y5D8, Q6ZQ82, Q7YQL5, Q7YQL6, Q8AVG0, Q8BPU7, Q8K0F1

Diamond homologs: A1IGU3, A1IGU4, A1IGU5, A4RF61, A5D7F8, A7E3N7, B0BNA1, B1V8A0, E2RP94, E7F1U2, F1LXF1, F1M0Z1, G5EC32, M0R4F8, O08641, O13736, O15068, O35179, O35180, O35964, O43307, O43586, O59679, O75791, O75962, O88811, P00527, P10569, P11274, P11433, P70297, P97814, Q09822, Q0KL02, Q10199, Q28923, Q28E95, Q2GT05, Q2KJB5, Q3LAC4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ARHGEF3	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1732 predictions. Top by Δscore:

Variant	Effect	Δscore
3:56729618:TTTAA:T	acceptor_gain	1.0000
3:56729619:TTAA:T	acceptor_gain	1.0000
3:56729620:TAA:T	acceptor_gain	1.0000
3:56729621:AA:A	acceptor_gain	1.0000
3:56729622:ACTAG:A	acceptor_loss	1.0000
3:56729623:C:CA	acceptor_loss	1.0000
3:56729623:C:CC	acceptor_gain	1.0000
3:56729624:T:C	acceptor_loss	1.0000
3:56732236:A:AC	donor_gain	1.0000
3:56732237:C:CC	donor_gain	1.0000
3:56732237:CTT:C	donor_gain	1.0000
3:56732237:CTTCT:C	donor_gain	1.0000
3:56732239:T:TA	donor_gain	1.0000
3:56732279:AG:A	donor_gain	1.0000
3:56732280:G:C	donor_gain	1.0000
3:56732285:A:AC	donor_gain	1.0000
3:56732286:C:CC	donor_gain	1.0000
3:56732286:CTT:C	donor_gain	1.0000
3:56732288:T:TA	donor_gain	1.0000
3:56732294:T:TA	donor_gain	1.0000
3:56732306:T:TA	donor_gain	1.0000
3:56732420:AGTTT:A	acceptor_gain	1.0000
3:56732421:GTTT:G	acceptor_gain	1.0000
3:56732422:TTT:T	acceptor_gain	1.0000
3:56732423:TT:T	acceptor_gain	1.0000
3:56732425:C:CC	acceptor_gain	1.0000
3:56732425:C:CG	acceptor_loss	1.0000
3:56732426:T:C	acceptor_loss	1.0000
3:56737182:TA:T	donor_loss	1.0000
3:56737183:A:AC	donor_gain	1.0000

AlphaMissense

3477 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:56729533:A:G	W440R	1.000
3:56729533:A:T	W440R	1.000
3:56745269:A:G	L269P	1.000
3:56745290:C:G	R262P	1.000
3:56745291:G:T	R262S	1.000
3:56745299:G:T	P259Q	1.000
3:56745308:A:G	L256P	1.000
3:56745308:A:T	L256H	1.000
3:56745318:A:G	W253R	1.000
3:56745318:A:T	W253R	1.000
3:56745320:A:T	L252H	1.000
3:56745326:A:G	L250P	1.000
3:56745332:C:G	R248P	1.000
3:56745333:G:T	R248S	1.000
3:56745334:G:C	S247R	1.000
3:56745334:G:T	S247R	1.000
3:56745336:T:G	S247R	1.000
3:56745337:A:C	F246L	1.000
3:56745337:A:T	F246L	1.000
3:56745339:A:G	F246L	1.000
3:56745352:A:C	C241W	1.000
3:56745353:C:T	C241Y	1.000
3:56745362:A:G	L238P	1.000
3:56745364:G:C	F237L	1.000
3:56745364:G:T	F237L	1.000
3:56745365:A:G	F237S	1.000
3:56745366:A:G	F237L	1.000
3:56745401:A:G	L225P	1.000
3:56745413:G:T	A221D	1.000
3:56751334:A:C	F167L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007613 (3:56899385 A>G), RS1000017976 (3:56904645 T>C), RS1000024288 (3:56900551 G>A), RS1000036886 (3:56944574 T>TTTTTC), RS1000043341 (3:56993033 C>G,T), RS1000056588 (3:57040613 T>A), RS1000066993 (3:56741066 T>C), RS1000079002 (3:56806716 A>G), RS1000082432 (3:56769832 GGTGT>G), RS1000088051 (3:56762316 T>C), RS1000107136 (3:56949734 C>T), RS1000111670 (3:57002931 G>A,C), RS1000120321 (3:57047225 G>A), RS1000135005 (3:56799201 A>G), RS1000138606 (3:56852459 G>A)

Disease associations

OMIM: gene MIM:612115 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

62 associations (top):

Study	Trait	p-value
GCST000305_2	Mean platelet volume	4.000000e-27
GCST000497_1	Mean platelet volume	6.000000e-31
GCST001022_2	Rheumatoid arthritis	2.000000e-06
GCST001335_10	Mean platelet volume	3.000000e-69
GCST001337_11	Platelet count	3.000000e-54
GCST001762_507	Obesity-related traits	1.000000e-06
GCST001783_1	Platelet count	4.000000e-09
GCST001783_2	Platelet count	1.000000e-19
GCST001783_3	Platelet count	9.000000e-13
GCST002184_5	Mean platelet volume	9.000000e-34
GCST002186_4	Platelet count	6.000000e-24
GCST003025_24	Attention function in attention deficit hyperactive disorder	8.000000e-06
GCST003383_3	Platelet count	2.000000e-13
GCST004599_293	Mean platelet volume	7.000000e-42
GCST004599_294	Mean platelet volume	2.000000e-32
GCST004599_76	Mean platelet volume	0.000000e+00
GCST004599_77	Mean platelet volume	1.000000e-29
GCST004603_247	Platelet count	2.000000e-19
GCST004603_248	Platelet count	9.000000e-301
GCST004603_249	Platelet count	1.000000e-19
GCST004607_256	Plateletcrit	2.000000e-21
GCST004619_27	Reticulocyte fraction of red cells	4.000000e-10
GCST004622_162	Reticulocyte count	4.000000e-10
GCST004627_97	Lymphocyte count	3.000000e-12
GCST005054_1	Platelet count	3.000000e-13
GCST005175_8	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	8.000000e-06
GCST005588_18	Idiopathic dilated cardiomyopathy	3.000000e-06
GCST005991_4	Platelet count	5.000000e-27
GCST006231_21	Mean arterial pressure	7.000000e-06
GCST007122_1	Multiple sclerosis and triglyceride levels (pleiotropy)	6.000000e-06

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007636	attention function measurement
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0004723	coronary artery calcification
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0006340	mean arterial pressure
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007984	platelet component distribution width
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
entinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, 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	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	affects cotreatment, increases expression	1
Fluvastatin	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1

Clinical trials (associated diseases)

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