RASGRP3

Summary

RASGRP3 (RAS guanyl releasing protein 3, HGNC:14545) is a protein-coding gene on chromosome 2p22.3, encoding Ras guanyl-releasing protein 3 (Q8IV61). Guanine nucleotide exchange factor (GEF) for Ras and Rap1.

The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers.

Source: NCBI Gene 25780 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 99 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001139488

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14545
Approved symbol	RASGRP3
Name	RAS guanyl releasing protein 3
Location	2p22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0846, GRP3, CalDAG-GEFIII
Ensembl gene	ENSG00000152689
Ensembl biotype	protein_coding
OMIM	609531
Entrez	25780

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 38 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000402538, ENST00000403687, ENST00000407811, ENST00000419772, ENST00000423159, ENST00000425210, ENST00000437184, ENST00000442390, ENST00000444784, ENST00000468856, ENST00000477927, ENST00000479528, ENST00000482731, ENST00000482857, ENST00000484909, ENST00000490150, ENST00000494927, ENST00000497723, ENST00000850562, ENST00000850563, ENST00000884675, ENST00000884676, ENST00000884677, ENST00000884678, ENST00000884679, ENST00000884680, ENST00000884681, ENST00000884682, ENST00000884683, ENST00000884684, ENST00000884685, ENST00000884686, ENST00000967275, ENST00000967276, ENST00000967277, ENST00000967278, ENST00000967279, ENST00000967280, ENST00000967281, ENST00000967282, ENST00000967283, ENST00000967284, ENST00000967285, ENST00000967286, ENST00000967287, ENST00000967288, ENST00000967289, ENST00000967290

RefSeq mRNA: 10 — MANE Select: NM_001139488 NM_001139488, NM_001349975, NM_001349976, NM_001349977, NM_001349978, NM_001349979, NM_001349980, NM_001349981, NM_015376, NM_170672

CCDS: CCDS46256, CCDS54346

Canonical transcript exons

ENST00000403687 — 18 exons

Exon	Start	End
ENSE00001006680	33549604	33549751
ENSE00001006681	33558211	33558336
ENSE00001070264	33520553	33520684
ENSE00001163155	33539094	33539210
ENSE00001253850	33555531	33555567
ENSE00001305152	33523879	33524052
ENSE00001329894	33524432	33524548
ENSE00001345943	33516542	33516644
ENSE00001408042	33558672	33559030
ENSE00001433633	33511710	33511842
ENSE00001480391	33519952	33520014
ENSE00001627226	33476649	33476707
ENSE00001949262	33562729	33564731
ENSE00003526146	33515010	33515206
ENSE00003600037	33543512	33543627
ENSE00003620627	33534323	33534400
ENSE00003672623	33527137	33527412
ENSE00003787417	33521955	33522102

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8943 / max 639.5387, expressed in 1005 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19694	5.8885	689
19692	2.3008	506
19682	1.6017	348
19693	1.5896	397
19683	0.3551	167
19690	0.3414	185
19691	0.2617	134
19689	0.1884	109
19687	0.1590	39
19688	0.0772	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	96.70	gold quality
inferior vagus X ganglion	UBERON:0005363	96.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.85	gold quality
spinal cord	UBERON:0002240	95.19	gold quality
subthalamic nucleus	UBERON:0001906	94.82	gold quality
medial globus pallidus	UBERON:0002477	93.92	gold quality
globus pallidus	UBERON:0001875	93.27	gold quality
superior vestibular nucleus	UBERON:0007227	91.93	gold quality
medulla oblongata	UBERON:0001896	91.48	gold quality
pons	UBERON:0000988	91.29	gold quality
heart left ventricle	UBERON:0002084	90.54	gold quality
lymph node	UBERON:0000029	90.30	gold quality
cardiac ventricle	UBERON:0002082	90.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.81	gold quality
midbrain	UBERON:0001891	89.79	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.77	gold quality
right atrium auricular region	UBERON:0006631	89.71	gold quality
substantia nigra	UBERON:0002038	89.69	gold quality
apex of heart	UBERON:0002098	89.57	gold quality
tonsil	UBERON:0002372	89.17	gold quality
vermiform appendix	UBERON:0001154	88.97	gold quality
lateral globus pallidus	UBERON:0002476	88.89	gold quality
ventral tegmental area	UBERON:0002691	88.77	gold quality
cardiac atrium	UBERON:0002081	88.51	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.20	gold quality
heart	UBERON:0000948	87.88	gold quality
caecum	UBERON:0001153	87.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.53	gold quality
substantia nigra pars compacta	UBERON:0001965	86.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.17	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	703.90
E-HCAD-4	yes	44.33
E-MTAB-8142	yes	14.78
E-MTAB-9067	yes	11.66
E-ANND-3	yes	10.56
E-MTAB-10553	yes	8.31
E-ENAD-20	no	14.10
E-CURD-112	no	2.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB5

miRNA regulators (miRDB)

78 targeting RASGRP3, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-12124	99.68	69.17	2700

Literature-anchored findings (GeneRIF, showing 13)

• A vascular gene trap screen defines RASGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters. (PMID:15572660)
• studies support the hypothesis that RasGRP phosphorylation by PKC is a mechanism that integrates DAG signaling systems in T and B cells (PMID:15657177)
• dynein light chain 1 represents a novel anchoring protein for RasGRP3 that may regulate subcellular localization of the exchange factor (PMID:17012239)
• Significant associations were found for the single nucleotide polymorphism rs13385731 of RasGRP3 with malar rash, discoid rash, and antinuclear antibody in patients with systemic lupus erythematosus (PMID:20516000)
• RasGRP3 contributes to the malignant phenotype of prostate cancer cells and may constitute a novel therapeutic target for human prostate cancer. (PMID:20876802)
• The identification of the role of RasGRP3 in melanoma highlights its importance, as a Ras activator, in the phosphoinositide signaling pathway in human melanoma. (PMID:21602881)
• Knockdown of RasGRP3 inhibited proliferation in prostate neoplasms. (PMID:24418912)
• Ras activator RasGRP3 may have a role in the pathological behavior of breast cancer cells and may constitute a therapeutic target for human breast cancer. (PMID:24779681)
• RasGRP3 mediates ERK MAPK pathway activation in GNAQ mutant uveal melanoma. (PMID:28486107)
• these data show that RasGRP3 exerts its oncogenic effect in papillary thyroid cancer through Akt-mediated MDM2 activation. (PMID:28864115)
• The marked differences between RasGRP3 and RasGRP1 in membrane interaction necessarily will contribute to their different behavior in cells. (PMID:28912101)
• In conclusion, these findings provide a new insight into the upregulation of RasGRP3 involved in Notch pathway activation in the development of esophageal squamous cell carcinoma , especially under nutrient deprivation. (PMID:29048643)
• RasGRP3, a Ras guanyl releasing protein 3 that contributes to malignant proliferation and aggressiveness in human esophageal squamous cell carcinoma (PMID:29461644)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rasgrp3	ENSDARG00000077864
mus_musculus	Rasgrp3	ENSMUSG00000071042
rattus_norvegicus	Rasgrp3	ENSRNOG00000032703

Paralogs (24): RASGRF1 (ENSG00000058335), RASGRP2 (ENSG00000068831), RAPGEF3 (ENSG00000079337), RAPGEF4 (ENSG00000091428), SOS2 (ENSG00000100485), RAPGEF1 (ENSG00000107263), RAPGEFL1 (ENSG00000108352), RAPGEF2 (ENSG00000109756), RASGRF2 (ENSG00000113319), SOS1 (ENSG00000115904), RALGPS2 (ENSG00000116191), RAPGEF5 (ENSG00000136237), RALGPS1 (ENSG00000136828), RASGEF1B (ENSG00000138670), RGL1 (ENSG00000143344), RASGEF1C (ENSG00000146090), RAPGEF6 (ENSG00000158987), RGL4 (ENSG00000159496), RALGDS (ENSG00000160271), RASGRP4 (ENSG00000171777), RASGRP1 (ENSG00000172575), RASGEF1A (ENSG00000198915), RGL3 (ENSG00000205517), RGL2 (ENSG00000237441)

Protein

Protein identifiers

Ras guanyl-releasing protein 3 — Q8IV61 (reviewed: Q8IV61)

Alternative names: Calcium and DAG-regulated guanine nucleotide exchange factor III, Guanine nucleotide exchange factor for Rap1

All UniProt accessions (7): Q8IV61, C9IYA5, C9J9C9, C9JSS2, C9JWP0, C9K0P4, H7C352

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) for Ras and Rap1.

Similarity. Belongs to the RASGRP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IV61-1	1	yes
Q8IV61-2	2

RefSeq proteins (10): NP_001132960, NP_001336904, NP_001336905, NP_001336906, NP_001336907, NP_001336908, NP_001336909, NP_001336910, NP_056191, NP_733772 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000651	Ras-like_Gua-exchang_fac_N	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008937	Ras-like_GEF	Family
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR020454	DAG/PE-bd	Domain
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00130, PF00617, PF13499

UniProt features (18 total): binding site 9, domain 4, chain 1, splice variant 1, sequence variant 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV61-F1	70.51	0.33

Functional residue map

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

Ligand- & substrate-binding residues (9): 439; 444; 462; 464; 466; 473; 433; 435; 437

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1169092	Activation of RAS in B cells
R-HSA-5673001	RAF/MAP kinase cascade

MSigDB gene sets: 273 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, ZHAN_MULTIPLE_MYELOMA_PR_DN, LU_IL4_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, KEGG_MAPK_SIGNALING_PATHWAY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, MEF2_02, GOMF_GTPASE_BINDING, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, GATA1_03, MAF_Q6, RYTTCCTG_ETS2_B

GO Biological Process (3): MAPK cascade (GO:0000165), small GTPase-mediated signal transduction (GO:0007264), Ras protein signal transduction (GO:0007265)

GO Molecular Function (10): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), kinase binding (GO:0019900), diacylglycerol binding (GO:0019992), small GTPase binding (GO:0031267), protein binding (GO:0005515), GTPase regulator activity (GO:0030695), metal ion binding (GO:0046872)

GO Cellular Component (4): plasma membrane (GO:0005886), guanyl-nucleotide exchange factor complex (GO:0032045), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Downstream signaling events of B Cell Receptor (BCR)	1
MAPK1/MAPK3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	2
GTPase regulator activity	2
GTPase activity	2
cellular anatomical structure	2
small GTPase-mediated signal transduction	1
GTP binding	1
GDP binding	1
enzyme activator activity	1
metal ion binding	1
transition metal ion binding	1
enzyme binding	1
lipid binding	1
GTPase binding	1
binding	1
nucleoside-triphosphatase regulator activity	1
cation binding	1
membrane	1
cell periphery	1
intracellular protein-containing complex	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASGRP3	DGKI	O75912	806
RASGRP3	CYTH3	O43739	678
RASGRP3	RAP1A	P10113	650
RASGRP3	HRAS	P01112	454
RASGRP3	RABIF	P47224	449
RASGRP3	TRANK1	O15050	447
RASGRP3	ZEB1	P37275	442
RASGRP3	HSPB3	Q12988	438
RASGRP3	SLC15A4	Q8N697	433
RASGRP3	GBP2	P32456	412
RASGRP3	SIPA1	Q96FS4	410
RASGRP3	IRF7	Q92985	407
RASGRP3	CSF2	P04141	404
RASGRP3	RRAS	P10301	396
RASGRP3	PRKCQ	Q04759	393

IntAct

17 interactions, top by confidence:

A	B	Type	Score
DYNLL2	RASGRP3	psi-mi:“MI:0915”(physical association)	0.560
RASGRP3	DYNLL2	psi-mi:“MI:0915”(physical association)	0.560
RFT1	RASGRP3	psi-mi:“MI:0915”(physical association)	0.560
RASGRP3	RFT1	psi-mi:“MI:0915”(physical association)	0.560
RASGRP3	HSD17B11	psi-mi:“MI:0915”(physical association)	0.560
GET1	RASGRP3	psi-mi:“MI:0915”(physical association)	0.560
RASGRP3	SULT1C2	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
YWHAQ	RASGRP3	psi-mi:“MI:0915”(physical association)	0.000
RASGRP3	HSD17B11	psi-mi:“MI:0915”(physical association)	0.000
RASGRP3	GET1	psi-mi:“MI:0915”(physical association)	0.000
uxuA	RASGRP3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): DYNLL2 (Two-hybrid), RASGRP3 (Two-hybrid), RASGRP3 (Affinity Capture-MS), RASGRP3 (Biochemical Activity), RASGRP3 (Biochemical Activity), RASGRP3 (Biochemical Activity), RASGRP3 (Biochemical Activity), RASGRP3 (Biochemical Activity), RASGRP3 (Affinity Capture-Western), PRKCD (Affinity Capture-Western), WRB (Two-hybrid), HSD17B11 (Two-hybrid), RASGRP3 (Affinity Capture-Western), RASGRP3 (Affinity Capture-MS), RASGRP3 (Affinity Capture-Western)

ESM2 similar proteins: A0JM95, A1A4S6, A2A2Y4, A4II46, A4IJ06, A6NI28, B2RQE8, B5DFQ4, F1LVW7, O60879, O60890, O70566, O95267, P0C7A6, P0CAX5, Q02384, Q07889, Q07890, Q08DP6, Q0P4Q4, Q28EC1, Q4V7P7, Q566W7, Q5R6F6, Q5R803, Q5U4T3, Q62245, Q69ZK0, Q6DBW1, Q6DHR3, Q6NTL4, Q6PCS4, Q6Y5D8, Q6ZM89, Q7YQL5, Q7YQL6, Q8AVG0, Q8BHD4, Q8IV61, Q8N9B8

Diamond homologs: A4IJ06, A6N9I4, A8KBH6, O14795, O45818, O94806, O95267, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09215, P09216, P0C643, P10102, P10829, P10830, P13677, P13678, P15882, P16054, P17252, P20444, P23298, P24723, P27715, P28867, P30337, P34578, P34722, P34885, P52757, P63318, P68403, P68404, P83099

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCQ	up-regulates	RASGRP3	phosphorylation
CREB5	“down-regulates quantity by repression”	RASGRP3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3427 predictions. Top by Δscore:

Variant	Effect	Δscore
2:33436592:G:GA	donor_loss	1.0000
2:33511838:AACAG:A	donor_gain	1.0000
2:33511839:ACAG:A	donor_gain	1.0000
2:33511839:ACAGG:A	donor_loss	1.0000
2:33511840:CAG:C	donor_gain	1.0000
2:33511840:CAGGT:C	donor_loss	1.0000
2:33511841:AG:A	donor_gain	1.0000
2:33511841:AGG:A	donor_loss	1.0000
2:33511842:GG:G	donor_gain	1.0000
2:33511842:GGTA:G	donor_loss	1.0000
2:33511843:G:GG	donor_gain	1.0000
2:33511843:GTAA:G	donor_loss	1.0000
2:33515006:TTA:T	acceptor_loss	1.0000
2:33515007:TAGAG:T	acceptor_loss	1.0000
2:33515008:A:AG	acceptor_gain	1.0000
2:33515009:G:A	acceptor_loss	1.0000
2:33515009:G:GG	acceptor_gain	1.0000
2:33515009:GA:G	acceptor_gain	1.0000
2:33520681:GCAT:G	donor_gain	1.0000
2:33521953:A:AG	acceptor_gain	1.0000
2:33521954:G:GA	acceptor_gain	1.0000
2:33522055:GC:G	donor_gain	1.0000
2:33522056:C:G	donor_gain	1.0000
2:33522103:G:GG	donor_gain	1.0000
2:33523877:A:AG	acceptor_gain	1.0000
2:33523878:G:GA	acceptor_gain	1.0000
2:33523878:GTTC:G	acceptor_gain	1.0000
2:33527410:ACGG:A	donor_loss	1.0000
2:33527411:CGG:C	donor_loss	1.0000
2:33527412:GGT:G	donor_loss	1.0000

AlphaMissense

4588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:33522065:T:C	L160P	1.000
2:33524452:T:A	N237K	1.000
2:33524452:T:G	N237K	1.000
2:33527191:C:A	R288S	1.000
2:33549731:T:C	C508R	1.000
2:33549732:G:A	C508Y	1.000
2:33549733:C:G	C508W	1.000
2:33549741:G:A	C511Y	1.000
2:33549742:T:G	C511W	1.000
2:33555561:T:C	C525R	1.000
2:33520557:T:A	W81R	0.999
2:33520557:T:C	W81R	0.999
2:33522056:C:A	A157D	0.999
2:33523972:T:A	W204R	0.999
2:33523972:T:C	W204R	0.999
2:33523988:T:A	V209D	0.999
2:33524015:G:T	R218M	0.999
2:33524016:G:C	R218S	0.999
2:33524016:G:T	R218S	0.999
2:33524436:T:C	L232P	0.999
2:33524463:T:C	L241P	0.999
2:33524468:G:C	A243P	0.999
2:33524480:G:C	G247R	0.999
2:33524481:G:A	G247D	0.999
2:33524484:T:C	L248P	0.999
2:33524504:C:A	R255S	0.999
2:33524508:T:C	L256P	0.999
2:33527192:G:C	R288P	0.999
2:33527249:A:T	K307I	0.999
2:33527251:G:C	D308H	0.999

dbSNP variants (sampled 300 via entrez): RS1000023781 (2:33505946 C>G), RS1000047483 (2:33541544 T>C), RS1000053257 (2:33506283 A>G), RS1000101726 (2:33439712 G>A), RS1000109694 (2:33465522 CA>C), RS1000154984 (2:33461933 T>C), RS1000191726 (2:33485725 A>G), RS1000218057 (2:33501905 G>A,C), RS1000236680 (2:33454394 G>C,T), RS1000250691 (2:33459201 C>G), RS1000261849 (2:33524815 C>T), RS1000290569 (2:33562262 T>A,C,G), RS1000292150 (2:33490640 A>G), RS1000307079 (2:33460547 C>G), RS1000346736 (2:33434580 A>G)

Disease associations

OMIM: gene MIM:609531 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000390_1	Hypertension (young onset)	3.000000e-10
GCST000507_10	Systemic lupus erythematosus	1.000000e-15
GCST001795_29	Systemic lupus erythematosus	4.000000e-06
GCST003461_2	IgG response to Plasmodium falciparum antigens (GLURP, MSP2 FC27, MSP2 3D7)	8.000000e-06
GCST003599_13	Systemic lupus erythematosus	1.000000e-06
GCST003622_57	Systemic lupus erythematosus	4.000000e-06
GCST003783_1	Multiple system atrophy (pathologically confirmed)	7.000000e-06
GCST003812_5	Non-response to antidepressants and depression	2.000000e-06
GCST005532_2	Sjögren’s syndrome	3.000000e-06
GCST005752_106	Systemic lupus erythematosus	1.000000e-06
GCST005987_25	Albumin-globulin ratio	6.000000e-12
GCST005990_40	Non-albumin protein levels	8.000000e-15
GCST006460_3	Bronchopulmonary dysplasia in preterm infants	6.000000e-06
GCST009391_648	Metabolite levels	2.000000e-06
GCST011956_64	Systemic lupus erythematosus	1.000000e-33

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007812	Plasmodium falciparum antigen IgG measurement
EFO:0005128	albumin:globulin ratio measurement
EFO:0010505	isocitrate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3638 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,362 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362

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

ChEMBL bioactivities

102 potent at pChembl≥5 of 102 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.74	Ki	0.18	nM	CHEMBL519741
9.70	Ki	0.2	nM	CHEMBL530110
9.48	Ki	0.33	nM	CHEMBL519741
9.47	Ki	0.34	nM	CHEMBL3289012
9.28	Ki	0.53	nM	CHEMBL4160361
9.28	Ki	0.52	nM	CHEMBL488872
9.15	Ki	0.7	nM	CHEMBL488667
9.14	Ki	0.72	nM	CHEMBL472007
9.08	Ki	0.84	nM	CHEMBL519741
9.00	Ki	1.01	nM	CHEMBL4160647
8.97	Ki	1.07	nM	CHEMBL4162516
8.96	Ki	1.09	nM	CHEMBL4163130
8.95	Ki	1.12	nM	CHEMBL3289014
8.91	Ki	1.22	nM	CHEMBL3289013
8.81	Ki	1.54	nM	CHEMBL4174397
8.80	Ki	1.6	nM	CHEMBL472522
8.79	Ki	1.63	nM	CHEMBL3289011
8.78	Ki	1.67	nM	CHEMBL4174723
8.77	Ki	1.7	nM	CHEMBL529000
8.76	Ki	1.75	nM	CHEMBL4169454
8.74	Ki	1.81	nM	CHEMBL4167589
8.74	Ki	1.8	nM	CHEMBL511820
8.73	Ki	1.87	nM	CHEMBL4160540
8.67	Ki	2.15	nM	CHEMBL4161221
8.65	Ki	2.25	nM	CHEMBL4175934
8.65	Ki	2.22	nM	CHEMBL519398
8.64	Ki	2.3	nM	CHEMBL471153
8.57	Ki	2.69	nM	CHEMBL4172461
8.56	Ki	2.73	nM	CHEMBL4175128
8.55	Ki	2.8	nM	CHEMBL4165117
8.54	Ki	2.86	nM	CHEMBL4163809
8.52	Ki	3.03	nM	CHEMBL4167900
8.48	Ki	3.3	nM	CHEMBL488674
8.45	Ki	3.58	nM	CHEMBL4175761
8.43	Ki	3.7	nM	CHEMBL472521
8.42	Ki	3.8	nM	CHEMBL488675
8.41	Ki	3.9	nM	CHEMBL472002
8.38	Ki	4.17	nM	CHEMBL461754
8.37	Ki	4.32	nM	CHEMBL4161062
8.37	Ki	4.26	nM	CHEMBL4175333
8.34	Ki	4.6	nM	CHEMBL488871
8.33	Ki	4.68	nM	CHEMBL452307
8.32	Ki	4.76	nM	CHEMBL4171253
8.29	Ki	5.07	nM	CHEMBL488667
8.28	Ki	5.3	nM	CHEMBL4167264
8.28	Ki	5.3	nM	CHEMBL472001
8.17	Ki	6.7	nM	CHEMBL488668
8.15	Ki	7	nM	CHEMBL461374
8.14	Ki	7.22	nM	CHEMBL4167457
8.13	Ki	7.48	nM	CHEMBL508870

PubChem BioAssay actives

102 with measured affinity, of 130 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 2-propylpentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0002	uM
[(4E)-2-(hydroxymethyl)-5-oxo-4-(pyridin-2-ylmethylidene)oxolan-2-yl]methyl 4-methyl-2-(2-methylpropyl)pentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0002	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-5-yl)methylidene]-5-oxooxolan-2-yl]methyl 2-propylpentanoate	1152264: Displacement of [3H]PDBu from recombinant human GFP-tagged RasGRP3 expressed in Escherichia coli BL21 after 5 mins by scintillation counting analysis in presence of phosphatidylserine	ki	0.0003	uM
[(4E)-4-[(4-chlorophenyl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0005	uM
[(4E)-2-(hydroxymethyl)-5-oxo-4-(quinolin-3-ylmethylidene)oxolan-2-yl]methyl 2-propylpentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0005	uM
[(4E)-2-(hydroxymethyl)-5-oxo-4-(pyridin-2-ylmethylidene)oxolan-2-yl]methyl 2-propylpentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0007	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 4-methyl-2-(2-methylpropyl)pentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0007	uM
[(4E)-4-[(5-chloro-1-methylindol-3-yl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0010	uM
[(4E)-4-[[4-(dimethylamino)phenyl]methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0011	uM
[(4E)-2-(hydroxymethyl)-4-[(4-methoxyphenyl)methylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0011	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-7-yl)methylidene]-5-oxooxolan-2-yl]methyl 2-propylpentanoate	1152264: Displacement of [3H]PDBu from recombinant human GFP-tagged RasGRP3 expressed in Escherichia coli BL21 after 5 mins by scintillation counting analysis in presence of phosphatidylserine	ki	0.0011	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-6-yl)methylidene]-5-oxooxolan-2-yl]methyl 2-propylpentanoate	1152264: Displacement of [3H]PDBu from recombinant human GFP-tagged RasGRP3 expressed in Escherichia coli BL21 after 5 mins by scintillation counting analysis in presence of phosphatidylserine	ki	0.0012	uM
[(4E)-2-(hydroxymethyl)-4-[(4-methoxyphenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-chlorobenzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0015	uM
[(4E)-2-(hydroxymethyl)-5-oxo-4-(pyridin-3-ylmethylidene)oxolan-2-yl]methyl 2-propylpentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0016	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-4-yl)methylidene]-5-oxooxolan-2-yl]methyl 2-propylpentanoate	1152264: Displacement of [3H]PDBu from recombinant human GFP-tagged RasGRP3 expressed in Escherichia coli BL21 after 5 mins by scintillation counting analysis in presence of phosphatidylserine	ki	0.0016	uM
[(4E)-4-(1-benzothiophen-3-ylmethylidene)-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0017	uM
[(4E)-2-(hydroxymethyl)-5-oxo-4-(quinolin-2-ylmethylidene)oxolan-2-yl]methyl 2-propylpentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0017	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0018	uM
[(4E)-4-[[4-(dimethylamino)phenyl]methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-chlorobenzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0018	uM
[(4E)-2-(hydroxymethyl)-4-[(4-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 2-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0018	uM
[(4E)-4-[(1-butylindol-3-yl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0019	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 4-tert-butylcyclohexane-1-carboxylate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0022	uM
[(4E)-4-[(4-chlorophenyl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-methoxybenzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0022	uM
[(4E)-2-(hydroxymethyl)-4-[(4-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-nitrobenzoate	364367: Binding affinity to RasGRP3	ki	0.0022	uM
[(4E)-2-(hydroxymethyl)-4-[(4-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 3-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0023	uM
[(4E)-4-[(4-chlorophenyl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-chlorobenzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0027	uM
[(4E)-4-[(4-chlorophenyl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-(dimethylamino)benzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0027	uM
[(4E)-4-(1-benzofuran-3-ylmethylidene)-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0028	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl cyclohexanecarboxylate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0029	uM
[(4E)-2-(hydroxymethyl)-4-[[1-(2-methylpropyl)indol-3-yl]methylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0030	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 4-methoxybenzoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0033	uM
[(4E)-4-[[1-(cyclopropylmethyl)indol-3-yl]methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0036	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 4-(dimethylamino)benzoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0037	uM
[(4E)-2-(hydroxymethyl)-4-[(4-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0038	uM
[(4E)-2-(hydroxymethyl)-4-[(3-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 2-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0039	uM
[(4E)-2-(hydroxymethyl)-4-[(4-methoxyphenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-methoxybenzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0042	uM
[(4Z)-4-(1-benzothiophen-3-ylmethylidene)-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0043	uM
[(4Z)-4-[(5-chloro-1-methylindol-3-yl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0043	uM
[(4Z)-2-(hydroxymethyl)-5-oxo-4-(quinolin-2-ylmethylidene)oxolan-2-yl]methyl 2-propylpentanoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0046	uM
[(4E)-4-[[4-(dimethylamino)phenyl]methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0047	uM
[(4E)-2-(hydroxymethyl)-4-[(5-methoxy-1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0048	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl heptanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0053	uM
[(4E)-2-(hydroxymethyl)-4-[(3-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 3-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0053	uM
[(4E)-2-(hydroxymethyl)-4-[(4-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-methoxybenzoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0067	uM
[(4E)-2-(hydroxymethyl)-4-[(4-methoxyphenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-(dimethylamino)benzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0070	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindazol-3-yl)methylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0072	uM
[(4E)-4-[[4-(dimethylamino)phenyl]methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-methoxybenzoate	1505438: Displacement of [3H]PDBu from full length MBP-tagged human RasGRP3 expressed in Escherichia coli BL21 (DE3) after 5 mins by scintillation counting	ki	0.0075	uM
[(4E)-2-(hydroxymethyl)-4-[(3-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0080	uM
[(4E)-2-(hydroxymethyl)-5-oxo-4-(quinolin-2-ylmethylidene)oxolan-2-yl]methyl 4-methoxybenzoate	365160: Displacement of [3H]PDBu from RasGRP3 expressed in cells	ki	0.0082	uM
[(4E)-2-(hydroxymethyl)-4-[(2-nitrophenyl)methylidene]-5-oxooxolan-2-yl]methyl 2-(dimethylamino)benzoate	364367: Binding affinity to RasGRP3	ki	0.0094	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	decreases expression, decreases methylation, affects expression	2
Antirheumatic Agents	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
chromium hexavalent ion	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
ormosil	affects binding, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Catechin	decreases expression, affects cotreatment	1
Chelating Agents	decreases expression, affects binding	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2034158	Binding	Modulation of RASGRP3 in human K562 cells assessed as induction of protein activity after 24 hrs by Western blotting analysis	Role of the C8 gem-dimethyl group of bryostatin 1 on its unique pattern of biological activity. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1H8	Abcam A-549 RASGRP3 KO 2	Cancer cell line	Male
CVCL_B2PR	Abcam A-549 RASGRP3 KO 1	Cancer cell line	Male
CVCL_E0MJ	Ubigene HeLa RASGRP3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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