RASGRF2

Summary

RASGRF2 (Ras protein specific guanine nucleotide releasing factor 2, HGNC:9876) is a protein-coding gene on chromosome 5q14.1, encoding Ras-specific guanine nucleotide-releasing factor 2 (O14827). Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP.

RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways.

Source: NCBI Gene 5924 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 143 total
• MANE Select transcript: NM_006909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9876
Approved symbol	RASGRF2
Name	Ras protein specific guanine nucleotide releasing factor 2
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	GRF2, Ras-GRF2
Ensembl gene	ENSG00000113319
Ensembl biotype	protein_coding
OMIM	606614
Entrez	5924

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000265080, ENST00000502677, ENST00000503795, ENST00000512186, ENST00000514946, ENST00000638442, ENST00000933988

RefSeq mRNA: 1 — MANE Select: NM_006909 NM_006909

CCDS: CCDS4052

Canonical transcript exons

ENST00000265080 — 27 exons

Exon	Start	End
ENSE00000757234	81180175	81180281
ENSE00000757236	81201330	81201442
ENSE00000757237	81206845	81206905
ENSE00000757238	81207246	81207349
ENSE00000757240	81208354	81208438
ENSE00000757241	81212366	81212563
ENSE00000757242	81215876	81215955
ENSE00000757248	81225678	81230162
ENSE00000971627	81092801	81092961
ENSE00000971630	81108996	81109078
ENSE00000971631	81112610	81112858
ENSE00000971632	81113538	81113920
ENSE00000971633	81123642	81123767
ENSE00000971634	81127074	81127163
ENSE00002074094	80960363	80961026
ENSE00003487205	81219710	81219778
ENSE00003508651	81085802	81085911
ENSE00003519017	81068032	81068179
ENSE00003557716	81070492	81070581
ENSE00003594601	81042877	81042983
ENSE00003596182	81086835	81086953
ENSE00003602674	81094856	81094992
ENSE00003616581	81094296	81094362
ENSE00003618584	81080596	81080789
ENSE00003641755	81073199	81073452
ENSE00003679997	81217356	81217473
ENSE00003692189	81080121	81080200

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 98.25.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6051 / max 108.5483, expressed in 703 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57332	2.4462	578
57333	1.4545	443
57329	0.2049	100
57328	0.1935	64
57331	0.1457	71
57334	0.0958	49
57330	0.0645	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.28	gold quality
endothelial cell	CL:0000115	93.86	gold quality
sural nerve	UBERON:0015488	90.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.76	gold quality
prefrontal cortex	UBERON:0000451	89.38	gold quality
corpus callosum	UBERON:0002336	88.79	gold quality
superior frontal gyrus	UBERON:0002661	88.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.29	gold quality
occipital lobe	UBERON:0002021	88.28	gold quality
frontal cortex	UBERON:0001870	88.10	gold quality
frontal lobe	UBERON:0016525	88.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.67	gold quality
primary visual cortex	UBERON:0002436	87.63	gold quality
spinal cord	UBERON:0002240	87.37	gold quality
pigmented layer of retina	UBERON:0001782	86.80	gold quality
retina	UBERON:0000966	86.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.77	gold quality
neocortex	UBERON:0001950	86.56	gold quality
parietal lobe	UBERON:0001872	86.03	gold quality
right frontal lobe	UBERON:0002810	85.83	gold quality
cerebral cortex	UBERON:0000956	85.65	gold quality
tibia	UBERON:0000979	85.62	gold quality
postcentral gyrus	UBERON:0002581	84.83	gold quality
anterior cingulate cortex	UBERON:0009835	84.45	gold quality
left ovary	UBERON:0002119	83.78	gold quality
adipose tissue	UBERON:0001013	83.57	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.45	gold quality
omental fat pad	UBERON:0010414	83.10	gold quality
peritoneum	UBERON:0002358	83.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting RASGRF2, 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-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 15)

• RasGRF family exchange factors, both endogenous and ectopically expressed, are present in the endoplasmic reticulum but not in the Golgi complex (PMID:14749369)
• Aberrant methylation of RASGRF2 is associated with human non-small cell lung cancer (PMID:16596198)
• These results identify RasGRF2 as an additional component of the signaling machinery involved in T-cell receptor- and NF-AT-mediated immune responses. (PMID:17923690)
• Farnesylated but not geranylgeranylated TC21 can be activated by RasGRF2 due to its pleckstrin homology 1 domain, by a mechanism independent of localization & of its ability to associate to membranes. (PMID:19692568)
• These data reveal unexpected negative roles for Vav1 and RasGRF2 in different stages of T-cell lymphoma progression. (PMID:20011522)
• Demonstrate a role for RasGRF1/2 as negative regulators of Cdc42 activation, suppressing tumor cell movement, cytoskeletal dynamics and cell transformation. (PMID:21685891)
• RASGRF2 has a role in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse (PMID:23223532)
• Case-control studies reveal malignant mesothelioma risk associated with variants in the SDK1, CRTAM and RASGRF2 genes. (PMID:23827383)
• these results suggest that betaarrestin1 regulates rasgrf2 gene expression and Rac activation to affect membrane protrusion and cell migration and invasion. (PMID:24692549)
• Endoplasmic reticulum stress triggers a localized signaling module on the ER surface involving Nox4-dependent calcium mobilization, which directs local Ras activation through ER-associated, calcium-responsive RasGRF. (PMID:27856453)
• this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with Alcoholic Liver Cirrhosis in men, particularly in the subgroup of patients with alcohol dependence. The findings suggest the potential relevance of the RAS gene family in alcoholism and Alcoholic Liver Cirrhosis. (PMID:27992614)
• RASGRF2-int is significantly associated with drug addiction. (PMID:30249655)
• High RASGRF2 expression is associated with migration and invasion of colorectal cancer. (PMID:30359168)
• AnxA6 may be a reliable biomarker for distant relapse-free survival and response of triple negative breast cancer (TNBC) patients to chemotherapy, and that the reciprocal expression of AnxA6 and GRF2 can reliably delineate TNBCs into rapidly growing and invasive subsets which may be more relevant for subset-specific therapeutic interventions. (PMID:32298357)
• Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients. (PMID:37029817)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rasgrf2b	ENSDARG00000002816
danio_rerio	rasgrf2a	ENSDARG00000075054
mus_musculus	Rasgrf2	ENSMUSG00000021708
rattus_norvegicus	Rasgrf2	ENSRNOG00000056151

Paralogs (24): RASGRF1 (ENSG00000058335), RASGRP2 (ENSG00000068831), RAPGEF3 (ENSG00000079337), RAPGEF4 (ENSG00000091428), SOS2 (ENSG00000100485), RAPGEF1 (ENSG00000107263), RAPGEFL1 (ENSG00000108352), RAPGEF2 (ENSG00000109756), SOS1 (ENSG00000115904), RALGPS2 (ENSG00000116191), RAPGEF5 (ENSG00000136237), RALGPS1 (ENSG00000136828), RASGEF1B (ENSG00000138670), RGL1 (ENSG00000143344), RASGEF1C (ENSG00000146090), RASGRP3 (ENSG00000152689), RAPGEF6 (ENSG00000158987), RGL4 (ENSG00000159496), RALGDS (ENSG00000160271), RASGRP4 (ENSG00000171777), RASGRP1 (ENSG00000172575), RASGEF1A (ENSG00000198915), RGL3 (ENSG00000205517), RGL2 (ENSG00000237441)

Protein

Protein identifiers

Ras-specific guanine nucleotide-releasing factor 2 — O14827 (reviewed: O14827)

Alternative names: Ras guanine nucleotide exchange factor 2

All UniProt accessions (4): O14827, A0A1W2PP99, A0A2X0SFL3, D6RAS9

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation.

Subunit / interactions. Homooligomer and heterooligomer with RASGRF1. Interacts with Ras and RAC1. Interacts in a calcium-dependent manner with calmodulin. Interacts with CDK5R1 and EPB49. Interacts with the AMPA receptor through GRIA1. Interacts with microtubules.

Subcellular location. Cytoplasm. Cell membrane. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed with higher expression in brain, followed by heart, lung, pancreas and kidney. Detected in placenta. Expressed in brain and lung (at protein level).

Post-translational modifications. Phosphorylated by CDK5; down-regulates RASGRF2-mediated RAC1 activation. Ubiquitinated upon interaction with Ras. Ubiquitination leads to degradation through the 26S proteasome.

Domain organisation. The Ras-GEF domain and the N-terminal Ras-GEF domain form a Ras-binding site and mediate Ras activation. The IQ domain mediates the calcium-dependent interaction with calmodulin but is dispensable for the Ras-GEF activity. The DH (DBL-homology) domain mediates interaction with RASGRF1 and EPB49 and is required for RAC1 activation.

RefSeq proteins (1): NP_008840* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR000651	Ras-like_Gua-exchang_fac_N	Domain
IPR001849	PH_domain	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR008937	Ras-like_GEF	Family
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019804	Ras_G-nucl-exch_fac_CS	Conserved_site
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily

Pfam: PF00169, PF00617, PF00618, PF00621

UniProt features (28 total): modified residue 7, domain 6, region of interest 4, sequence variant 4, compositionally biased region 3, chain 1, coiled-coil region 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14827-F1	73.97	0.32

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 (7): 726, 727, 737, 746, 848, 852, 972

Mutagenesis-validated functional residues (1):

Position	Phenotype
737	loss of phosphorylation by cdk5.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 183 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, AREB6_01, AP4_Q6, HNF1_Q6, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, MYOD_Q6

GO Biological Process (6): Ras protein signal transduction (GO:0007265), response to endoplasmic reticulum stress (GO:0034976), regulation of small GTPase mediated signal transduction (GO:0051056), long-term synaptic potentiation (GO:0060291), postsynaptic modulation of chemical synaptic transmission (GO:0099170), small GTPase-mediated signal transduction (GO:0007264)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), calmodulin binding (GO:0005516)

GO Cellular Component (8): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	3
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
MAPK1/MAPK3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
small GTPase-mediated signal transduction	2
cytoplasm	2
synapse	2
cellular response to stress	1
regulation of intracellular signal transduction	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
modulation of chemical synaptic transmission	1
postsynapse	1
intracellular signaling cassette	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
protein binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASGRF2	GRIN2A	Q12879	781
RASGRF2	MCF2	P10911	687
RASGRF2	GRIN2B	Q13224	599
RASGRF2	CDC42	P21181	591
RASGRF2	TM6SF1	Q9BZW5	574
RASGRF2	RASA1	P20936	563
RASGRF2	PLEK2	Q9NYT0	508
RASGRF2	RHOA	P06749	506
RASGRF2	SHC1	P29353	493
RASGRF2	RHOC	P08134	489
RASGRF2	PLEK	P08567	481
RASGRF2	RABIF	P47224	475
RASGRF2	PLCG1	P19174	453
RASGRF2	MAPK3	P27361	447
RASGRF2	ARHGEF19	Q8IW93	446

IntAct

9 interactions, top by confidence:

A	B	Type	Score
RASGRF2	SNRPA	psi-mi:“MI:0914”(association)	0.350
DNMBP	RASGRF2	psi-mi:“MI:0914”(association)	0.350
	RASGRF2	psi-mi:“MI:0915”(physical association)	0.000
PANK2	RASGRF2	psi-mi:“MI:0915”(physical association)	0.000
DISC1	RASGRF2	psi-mi:“MI:0915”(physical association)	0.000
sucA	RASGRF2	psi-mi:“MI:0915”(physical association)	0.000
AKTIP	RASGRF2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): RASGRF2 (Affinity Capture-MS), PMVK (Affinity Capture-MS), EPPK1 (Affinity Capture-MS), RASGRF2 (Affinity Capture-MS), RASGRF2 (Two-hybrid), RASGRF2 (FRET), RASGRF2 (FRET), RASGRF2 (FRET), RASGRF2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), CTBP2 (Affinity Capture-MS), FGD3 (Affinity Capture-MS), NOSIP (Affinity Capture-MS), RSL24D1 (Affinity Capture-MS), SF3A2 (Affinity Capture-MS)

ESM2 similar proteins: A1Z7A6, A2CEA7, A8JQ65, B3M301, B3P8A3, B4I4Y1, B4NBP4, B4QSF0, B4R0A5, G5EBZ8, G5EEW9, G5EFD2, G5EFI8, O14827, O43150, O97902, P27671, P28818, P34400, P49809, P70392, Q13972, Q19857, Q1AAU6, Q21653, Q5W7F2, Q6NRL1, Q7SIG6, Q8BXK8, Q8MLZ5, Q8VHH5, Q94071, Q95RG8, Q96P47, Q99JE4, Q9C6C3, Q9FIT8, Q9P246, Q9QWY8, Q9SMX5

Diamond homologs: A2AR50, A2CEA7, B0M0P8, B0UXH6, F1M386, F1MSG6, F1PBJ0, O14827, P27671, P28818, P70392, Q03385, Q03386, Q07889, Q07890, Q12967, Q13905, Q13972, Q3MIN7, Q3UYI5, Q4R7W3, Q54FF3, Q54PQ4, Q54TK8, Q552M5, Q55GH9, Q5JS13, Q5ZJK0, Q60695, Q86G47, Q86X27, Q8CHG7, Q8IS14, Q8IS15, Q8IS16, Q8IS18, Q8IS20, Q8IS21, Q8SSQ0, Q8SSW7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RASGRF2	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”
RASGRF2	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”
RASGRF2	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	118
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

5885 predictions. Top by Δscore:

Variant	Effect	Δscore
5:81042872:TCCAG:T	acceptor_loss	1.0000
5:81042875:A:AC	acceptor_loss	1.0000
5:81042875:A:AG	acceptor_gain	1.0000
5:81042876:G:GC	acceptor_gain	1.0000
5:81042876:GT:G	acceptor_gain	1.0000
5:81042876:GTAT:G	acceptor_gain	1.0000
5:81042876:GTATT:G	acceptor_gain	1.0000
5:81042979:GCCAG:G	donor_gain	1.0000
5:81042981:CAGGT:C	donor_loss	1.0000
5:81042984:G:C	donor_loss	1.0000
5:81042985:T:A	donor_loss	1.0000
5:81070579:AAGG:A	donor_loss	1.0000
5:81070581:GGT:G	donor_loss	1.0000
5:81070582:G:GA	donor_loss	1.0000
5:81073197:A:AG	acceptor_gain	1.0000
5:81073197:AG:A	acceptor_gain	1.0000
5:81073198:G:GC	acceptor_gain	1.0000
5:81073198:GG:G	acceptor_gain	1.0000
5:81073198:GGT:G	acceptor_gain	1.0000
5:81073198:GGTT:G	acceptor_gain	1.0000
5:81073198:GGTTC:G	acceptor_gain	1.0000
5:81073434:GCA:G	donor_gain	1.0000
5:81073437:G:GG	donor_gain	1.0000
5:81080116:TATA:T	acceptor_loss	1.0000
5:81080117:ATAGT:A	acceptor_gain	1.0000
5:81080118:T:G	acceptor_gain	1.0000
5:81080118:TAGT:T	acceptor_loss	1.0000
5:81080119:A:AG	acceptor_gain	1.0000
5:81080119:A:T	acceptor_loss	1.0000
5:81080119:AGT:A	acceptor_gain	1.0000

AlphaMissense

8198 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:81042958:T:A	W124R	1.000
5:81042958:T:C	W124R	1.000
5:81068085:T:C	L150P	1.000
5:81068169:T:C	L178P	1.000
5:81073215:G:C	R217P	1.000
5:81073217:G:A	G218R	1.000
5:81073217:G:C	G218R	1.000
5:81073218:G:A	G218E	1.000
5:81073220:T:A	W219R	1.000
5:81073220:T:C	W219R	1.000
5:81073222:G:C	W219C	1.000
5:81073222:G:T	W219C	1.000
5:81073226:T:C	C221R	1.000
5:81073230:G:C	R222T	1.000
5:81073230:G:T	R222I	1.000
5:81073231:A:C	R222S	1.000
5:81073231:A:T	R222S	1.000
5:81073238:T:A	W225R	1.000
5:81073238:T:C	W225R	1.000
5:81073239:G:C	W225S	1.000
5:81073240:G:C	W225C	1.000
5:81073240:G:T	W225C	1.000
5:81073389:T:C	M275T	1.000
5:81073395:C:A	A277D	1.000
5:81073397:A:C	S278R	1.000
5:81073399:C:A	S278R	1.000
5:81073399:C:G	S278R	1.000
5:81080134:T:C	F301L	1.000
5:81080135:T:C	F301S	1.000
5:81080135:T:G	F301C	1.000

dbSNP variants (sampled 300 via entrez): RS1000004198 (5:81115808 C>T), RS1000006670 (5:81166519 G>A), RS1000032937 (5:81041153 G>C), RS1000045157 (5:80998672 C>T), RS1000053125 (5:80988994 T>G), RS1000061364 (5:81073095 C>A), RS1000067595 (5:81080022 T>C), RS1000076586 (5:81220874 T>C), RS1000078087 (5:81165146 T>C), RS1000115447 (5:80995406 A>G), RS1000136437 (5:81164494 T>C), RS1000146988 (5:81135534 G>A), RS1000157299 (5:81097920 T>C), RS1000163497 (5:81075607 G>A), RS1000164076 (5:80974809 T>C)

Disease associations

OMIM: gene MIM:606614 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000903_2	Response to methylphenidate treatment in attention-deficit/hyperactivity disorder (blood pressure)	8.000000e-06
GCST001442_13	Orofacial clefts	4.000000e-06
GCST001959_11	Eating disorders (purging via substances)	1.000000e-07
GCST001960_6	Eating disorders	4.000000e-06
GCST002663_5	Superior frontal gyrus grey matter volume	4.000000e-06
GCST004862_52	Itch intensity from mosquito bite adjusted by bite size	4.000000e-06
GCST006288_320	Heel bone mineral density	8.000000e-11
GCST006288_535	Heel bone mineral density	8.000000e-14
GCST006411_6	Mucinous adenocarcinoma in colorectal cancer	5.000000e-06
GCST006979_111	Heel bone mineral density	2.000000e-39
GCST007317_1	Response to ketamine in bipolar disorder or major depression (dissociation effects)	2.000000e-07
GCST007323_6	Risk-taking tendency (4-domain principal component model)	5.000000e-09
GCST007324_68	Adventurousness	1.000000e-14
GCST007324_94	Adventurousness	6.000000e-09
GCST007325_256	General risk tolerance (MTAG)	2.000000e-09
GCST007325_289	General risk tolerance (MTAG)	3.000000e-17
GCST007327_100	Smoking status (ever vs never smokers)	2.000000e-09
GCST008553_2	Statin-induced myopathy (severe)	3.000000e-06
GCST008810_32	Smoking initiation (ever regular vs never regular)	4.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006516	superior frontal gyrus grey matter volume measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0009270	heel bone mineral density
EFO:0009361	colorectal mucinous adenocarcinoma
EFO:0009748	response to ketamine
EFO:0009750	dissociation measurement
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
mercuric bromide	increases expression, affects cotreatment	2
Copper	affects binding, decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
CGP 52608	increases reaction, affects binding	1
entinostat	affects cotreatment, 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
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	decreases expression, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1

Clinical trials (associated diseases)

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