PREX1

Summary

PREX1 (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1, HGNC:32594) is a protein-coding gene on chromosome 20q13.13, encoding Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein (Q8TCU6). Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP.

The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins.

Source: NCBI Gene 57580 — RefSeq curated summary.

At a glance

• GWAS associations: 39
• Clinical variants (ClinVar): 246 total
• MANE Select transcript: NM_020820

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32594
Approved symbol	PREX1
Name	phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1415, P-REX1
Ensembl gene	ENSG00000124126
Ensembl biotype	protein_coding
OMIM	606905
Entrez	57580

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000371941, ENST00000482556, ENST00000496915, ENST00000620554, ENST00000935959

RefSeq mRNA: 1 — MANE Select: NM_020820 NM_020820

CCDS: CCDS13410

Canonical transcript exons

ENST00000371941 — 40 exons

Exon	Start	End
ENSE00000845281	48632277	48632391
ENSE00000845283	48634676	48634775
ENSE00000845284	48636463	48636683
ENSE00000845285	48637711	48637752
ENSE00000845286	48639766	48639894
ENSE00000845287	48642168	48642258
ENSE00000845288	48642407	48642489
ENSE00000845289	48644409	48644497
ENSE00000845290	48645851	48646057
ENSE00000845291	48649300	48649576
ENSE00000845294	48649996	48650206
ENSE00000845295	48650894	48651055
ENSE00000845297	48651396	48651583
ENSE00000845300	48652586	48652706
ENSE00000845302	48653361	48653497
ENSE00000845304	48655290	48655375
ENSE00000845306	48657040	48657188
ENSE00000845308	48658136	48658228
ENSE00000845310	48659919	48660061
ENSE00000845312	48666283	48666355
ENSE00000845314	48676193	48676268
ENSE00000845316	48679360	48679409
ENSE00000845318	48679651	48679754
ENSE00000845320	48681235	48681335
ENSE00000845322	48688657	48688804
ENSE00000845324	48690947	48691096
ENSE00000845325	48692672	48692790
ENSE00000845327	48700753	48700886
ENSE00000845330	48708260	48708421
ENSE00000845331	48726290	48726391
ENSE00000845335	48745025	48745147
ENSE00000845336	48747809	48747880
ENSE00001244159	48734546	48734650
ENSE00001244624	48632496	48632639
ENSE00001456581	48827642	48827999
ENSE00003614436	48624252	48625927
ENSE00003632724	48627861	48627963
ENSE00003634050	48629449	48629621
ENSE00003637041	48627548	48627615
ENSE00003647525	48630728	48630794

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.1017 / max 325.6449, expressed in 1009 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187710	3.7124	996
187684	0.4419	60
187688	0.3111	59
187685	0.2390	61
187687	0.1642	49
187683	0.1569	56
187682	0.0549	35
187686	0.0215	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	97.99	gold quality
blood	UBERON:0000178	97.41	gold quality
corpus callosum	UBERON:0002336	97.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.15	gold quality
granulocyte	CL:0000094	97.01	gold quality
ganglionic eminence	UBERON:0004023	96.96	gold quality
spinal cord	UBERON:0002240	96.92	gold quality
right lung	UBERON:0002167	96.05	gold quality
subthalamic nucleus	UBERON:0001906	95.98	gold quality
lateral globus pallidus	UBERON:0002476	95.79	gold quality
substantia nigra	UBERON:0002038	95.66	gold quality
leukocyte	CL:0000738	95.61	gold quality
midbrain	UBERON:0001891	95.55	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.54	gold quality
monocyte	CL:0000576	95.45	gold quality
spleen	UBERON:0002106	95.02	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.80	gold quality
medulla oblongata	UBERON:0001896	94.70	gold quality
amygdala	UBERON:0001876	94.39	gold quality
putamen	UBERON:0001874	94.20	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.17	gold quality
superior vestibular nucleus	UBERON:0007227	94.03	gold quality
ventral tegmental area	UBERON:0002691	94.00	gold quality
Ammon’s horn	UBERON:0001954	93.54	gold quality
vermiform appendix	UBERON:0001154	93.52	gold quality
substantia nigra pars compacta	UBERON:0001965	93.43	gold quality
hypothalamus	UBERON:0001898	93.34	gold quality
caudate nucleus	UBERON:0001873	93.06	gold quality
upper lobe of left lung	UBERON:0008952	93.00	gold quality
ventricular zone	UBERON:0003053	92.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	27.57
E-CURD-119	yes	24.79
E-ANND-3	yes	16.62
E-CURD-112	no	2.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PRKDC, SP1

miRNA regulators (miRDB)

100 targeting PREX1, 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-4533	100.00	69.48	2758
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• P-Rex1 appears to be a coincidence detector in PtdIns(3,4,5)P3 and Gbetagamma signaling pathways that is particularly adapted to function downstream of heterotrimeric G proteins in neutrophils. (PMID:11955434)
• P-Rex1 is synergistically activated by PIP(3) and Gbetagamma and may act as a coincidence detector for these signaling molecules (PMID:12123595)
• P-Rex1 is regulated by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits (PMID:15545267)
• protein kinase A phosphorylates P-Rex1 andd inhibits the phosphatidylinositiol (3,4,5)-trisphosphate and Gbetagamma-mediated regulation of its activity (PMID:16301320)
• Endogenous P-Rex1 translocates to areas of Rac2 and cytoskeletal activation at the leading edge in response to chemoattractant stimuli in human neutrophils and that this translocation can be negatively modulated by activation of PKA and by cell adhesion. (PMID:17227822)
• P-Rex1 links mTOR signaling to Rac activation and cell migration (PMID:17565979)
• P-Rex1 membrane transport is mediated by G protein betagamma subunits and phosphoinositide 3-kinase (PMID:17698854)
• This study has identified P-Rex1 as a Rac3-guanine nucleotide exchange factor in neuronal cells that localises to, and regulates, actin cytoskeletal dynamics at the axonal growth cone to in turn regulate neurite differentiation. (PMID:18697831)
• P-Rex1-dependent activation of Rac promotes prostate cancer metastasis. (PMID:19305425)
• P-Rex1 is a key element in stromal cell-derived factor-1-induced angiogenic responses and signaling pathway. (PMID:20018810)
• S1P(1) signaling linked to cell migration is facilitated by a functional interaction with P-Rex1 via a mechanism that involves the maintenance of S1P(1) receptors at the cell membrane. (PMID:20036214)
• P-Rex1 is a critical component for formyl peptide receptor 1-mediated signaling leading to NADPH oxidase activation. (PMID:20074642)
• SNPs near PREX1 may contribute to T2 Diabetes susceptibility mediated through effects of adiposity in European Americans. (PMID:20650312)
• study reports the identification of P-Rex1, as a novel mediator in signalling by ErbB/HER receptors; correlation between high P-Rex1 expression and poor patient outcome in breast cancer was found (PMID:21042280)
• The P-Rex1 is highly overexpressed in human breast cancers and their derived cell lines, particularly those with high ErbB2 and ER expression. (PMID:21172654)
• Selective activation of Akt1 through mTORC2 and P-Rex1 regulates cancer cell migration, invasion and metastasis. (PMID:21339740)
• HDACs could regulate P-Rex1 gene transcription by interaction with Sp1 and by region-specific changes in histone acetylation within the P-Rex1 promoter (PMID:21636851)
• Demonstrate presence of P-Rex1 in platelets as well as its role in platelet secretion and aggregation induced by low-dose agonists for g-protein coupled receptors and by collagen. (PMID:22207728)
• We have identified a novel mechanism for direct activation of P-Rex1 through PP1alpha-dependent dephosphorylation. (PMID:22242915)
• Studies indicate relevance of P-Rex1 and P-Rex2a, in breast tumorigenesis, and suggest that the exchange factors Vav2 and Vav3 play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and metastasis. (PMID:23033535)
• These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes. (PMID:23382862)
• Cucurbitacin I also failed to affect the activation of P-Rex1 by heregulin. (PMID:23478800)
• Phosphorylation of P-Rex1 at serine 1169 participates in IGF-1R signaling in breast cancer cells. (PMID:23899556)
• PREX1 gene promoter hypomethylation is a prognostic marker of poor patient survival. (PMID:25248717)
• P-REX1 promotes both PI3K/AKT and MEK/ERK signaling in breast cancer. (PMID:25284585)
• The P-Rex1-Rac1 interface is critical for Rac1 activation in breast cancer cells. (PMID:26112412)
• findings suggest a vital role of P-Rex1 signaling in CA1 LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs (PMID:26621702)
• P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism. (PMID:26797121)
• An unexpected role for P-Rex1 and Rac1 activation in the genesis of prostate cancer stem cells and resistance to bevacizumab and sunitinib. (PMID:26923603)
• There is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis. (PMID:27351228)
• PREX1 overexpression reduced staurosporine-induced apoptosis whereas its shRNA knockdown promoted apoptosis in response to staurosporine or the anti-estrogen drug tamoxifen. (PMID:27358402)
• data point to multiple mechanisms of PREX1 negative regulation by PAKs within receptor tyrosine kinase and GPCR-stimulated signaling pathways (PMID:27481946)
• Authors suggest that control of P-Rex1 activity depends on a highly dynamic interplay among distinct signalling routes and its multisite phosphorylation is controlled by the action of different kinases. (PMID:27788493)
• PREX1 integrates dopamine receptor and phosphoinositide 3-kinase signaling to promote glioblastoma tumor cell invasion. (PMID:28051998)
• upon ligation of the T-cell antigen receptor (TCR), the TCR associates with and transactivates CXCR4 via phosphorylation of S339-CXCR4 in order to activate a PREX1-Rac1-signaling pathway that stabilizes interleukin-2(IL-2), IL-4, and IL-10 messenger RNA (mRNA) transcripts. (PMID:28694325)
• Data suggest that PREX1 and PREX2 share similarities in amino acid sequence, domain structure, activation by PIP(3) [phosphatidylinositol 3,4,5-triphosphate] and G-protein-coupled receptors beta/gamma subunits; expression of PREX1 and PREX2 is altered in many cancers. [REVIEW] (PMID:28710285)
• a novel role for GRK2 as a target of TCR signaling that is responsible for TCR-induced transactivation of CXCR4 and TCR-CXCR4 complex formation that signals via PI3Kgamma/PREX1 to mediate cytokine production. (PMID:30018141)
• GTPase-deficient G-ALPHA-qQL and Galpha13QL variants formed stable complexes with G protein beta gamma, impairing its interaction with P-REX1. (PMID:30446620)
• type I PKA regulatory subunits (RIalpha) interact with phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchange factor 1 (P-REX1), a chemotactic Rac guanine exchange factor (RacGEF). RIalpha CNB-B domain is critical for the interaction with P-REX1, which was increased in RIalpha mutants, such as the acrodysostosis-associated mutant, that activate P-REX1 at basal cAMP levels. (PMID:30530493)
• PREX1 is a favorable variable of prognosis for breast cancer patients. (PMID:31473760)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prex1	ENSDARG00000075793
mus_musculus	Prex1	ENSMUSG00000039621
rattus_norvegicus	Prex1	ENSRNOG00000006952

Paralogs (3): PREX2 (ENSG00000046889), DEPTOR (ENSG00000155792), GPR155 (ENSG00000163328)

Protein

Protein identifiers

Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein — Q8TCU6 (reviewed: Q8TCU6)

All UniProt accessions (3): A0A087WY11, Q8TCU6, H0YDZ4

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils.

Subunit / interactions. Interacts preferentially with RAC2. Interacts with RAC1. Interacts with AUTS2.

Subcellular location. Cytoplasm. Cytosol. Cell membrane.

Tissue specificity. Mainly expressed in peripheral blood leukocytes and brain. Expressed at intermediate level in spleen and lymph nodes, and weakly expressed in other tissues.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TCU6-1	1	yes
Q8TCU6-2	2
Q8TCU6-3	3

RefSeq proteins (1): NP_065871* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR000591	DEP_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001478	PDZ	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR051832	mTOR-Rac_regulators	Family
IPR055251	SOS1_NGEF_PH	Domain

Pfam: PF00610, PF00621, PF22697

UniProt features (125 total): strand 49, helix 44, sequence variant 7, turn 6, domain 5, modified residue 4, splice variant 4, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
5D3X	X-RAY DIFFRACTION	1.69
5D3V	X-RAY DIFFRACTION	1.85
5D3W	X-RAY DIFFRACTION	1.85
5D27	X-RAY DIFFRACTION	1.92
4YON	X-RAY DIFFRACTION	1.95
5D3Y	X-RAY DIFFRACTION	1.95
3QIK	X-RAY DIFFRACTION	2.29
6VSK	X-RAY DIFFRACTION	3.12
6PCV	ELECTRON MICROSCOPY	3.2
5FI1	X-RAY DIFFRACTION	3.2
7RX9	X-RAY DIFFRACTION	3.22
5FI0	X-RAY DIFFRACTION	3.28
8TUA	ELECTRON MICROSCOPY	4.1
7SYF	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCU6-F1	79.40	0.42

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 (4): 319, 1001, 1195, 1200

Function

Pathways and Gene Ontology

Reactome pathways

12 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-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle

MSigDB gene sets: 283 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_DENDRITE_DEVELOPMENT, GGGACCA_MIR133A_MIR133B, GCM_MAP4K4, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOBP_SUPEROXIDE_METABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_LEUKOCYTE_CHEMOTAXIS

GO Biological Process (16): superoxide metabolic process (GO:0006801), G protein-coupled receptor signaling pathway (GO:0007186), actin filament polymerization (GO:0030041), T cell differentiation (GO:0030217), positive regulation of cell migration (GO:0030335), neutrophil chemotaxis (GO:0030593), regulation of actin filament polymerization (GO:0030833), negative regulation of TOR signaling (GO:0032007), intracellular signal transduction (GO:0035556), neutrophil activation (GO:0042119), regulation of dendrite development (GO:0050773), regulation of small GTPase mediated signal transduction (GO:0051056), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), leukocyte activation (GO:0045321), positive regulation of cell adhesion (GO:0045785), reactive oxygen species metabolic process (GO:0072593)

GO Molecular Function (6): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), phospholipid binding (GO:0005543), enzyme binding (GO:0019899), protein serine/threonine kinase inhibitor activity (GO:0030291), protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), plasma membrane (GO:0005886), growth cone (GO:0030426), dendritic shaft (GO:0043198), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	10
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
signal transduction	2
intracellular anatomical structure	2
GTPase regulator activity	2
cytoplasm	2
reactive oxygen species metabolic process	1
G protein-coupled receptor activity	1
actin polymerization or depolymerization	1
protein polymerization	1
lymphocyte differentiation	1
T cell activation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
granulocyte chemotaxis	1
neutrophil migration	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
TOR signaling	1
regulation of TOR signaling	1
negative regulation of intracellular signal transduction	1
granulocyte activation	1
regulation of neuron projection development	1
dendrite development	1
regulation of developmental process	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
cell activation	1
immune system process	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
metabolic process	1
GTP binding	1
GDP binding	1
GTPase activity	1

Protein interactions and networks

STRING

1444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PREX1	RABIF	P47224	792
PREX1	RAC2	P15153	663
PREX1	RAC1	P15154	634
PREX1	PLEK	P08567	625
PREX1	PIK3CG	P48736	606
PREX1	S1PR1	P21453	605
PREX1	SUCLG2	Q96I99	589
PREX1	AKT1	P31749	574
PREX1	CDC42	P21181	550
PREX1	DOCK1	Q14185	539
PREX1	RHOG	P35238	485
PREX1	DOCK2	Q92608	483
PREX1	RHOA	P06749	476
PREX1	PLEK2	Q9NYT0	474
PREX1	ELMO2	Q96JJ3	474

IntAct

63 interactions, top by confidence:

A	B	Type	Score
RPTOR	MTOR	psi-mi:“MI:0914”(association)	0.980
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
MTOR	PREX1	psi-mi:“MI:0915”(physical association)	0.680
PREX1	MTOR	psi-mi:“MI:0915”(physical association)	0.680
MTOR	PREX1	psi-mi:“MI:0407”(direct interaction)	0.680
MTOR	PREX1	psi-mi:“MI:0914”(association)	0.680
RICTOR	PREX1	psi-mi:“MI:0915”(physical association)	0.620
PREX1	RAC1	psi-mi:“MI:0407”(direct interaction)	0.560
PREX1	CDC42	psi-mi:“MI:0407”(direct interaction)	0.560
RPTOR	PREX1	psi-mi:“MI:0915”(physical association)	0.560
MET	PREX1	psi-mi:“MI:0915”(physical association)	0.520
Akt1	PREX1	psi-mi:“MI:0915”(physical association)	0.500
PREX1	Akt1	psi-mi:“MI:0914”(association)	0.500
FRMPD4	PREX1	psi-mi:“MI:0407”(direct interaction)	0.440
RASSF6	PREX1	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	PREX1	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	PREX1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC4	PREX1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	PREX1	psi-mi:“MI:0407”(direct interaction)	0.440
PREX1	ATP2B4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (80): PREX1 (Synthetic Lethality), PREX1 (Synthetic Lethality), PREX1 (Affinity Capture-MS), PREX1 (Affinity Capture-MS), PREX1 (Affinity Capture-RNA), PREX1 (Affinity Capture-MS), PREX1 (Affinity Capture-MS), MTHFD1 (Affinity Capture-MS), STXBP1 (Affinity Capture-MS), DPYSL2 (Affinity Capture-MS), NCDN (Affinity Capture-MS), AP3B2 (Affinity Capture-MS), NCDN (Affinity Capture-Western), PREX1 (Affinity Capture-Western), PREX1 (Reconstituted Complex)

ESM2 similar proteins: A0A0G2JXN2, A2AWP8, O88842, O95267, P29590, P52734, P98174, Q1LY10, Q29RM4, Q2TBA3, Q3TAA7, Q3U0J8, Q3UTZ3, Q496Y0, Q4VX76, Q568M3, Q58D15, Q5BIM1, Q5JSP0, Q5R5M3, Q5R5T1, Q5REJ9, Q5W0U4, Q68FF6, Q69Z89, Q69ZK0, Q6PFY8, Q7TNM2, Q7Z4K8, Q7Z5H3, Q7Z6J4, Q80V85, Q8BY35, Q8BZ52, Q8C190, Q8N1F8, Q8TCU6, Q8WVR3, Q96JH8, Q99N48

Diamond homologs: A1CEE0, A1DFV9, A4R596, O75140, P61460, Q0CHV5, Q1E9Q9, Q2H0S0, Q2UMR9, Q4WHH4, Q54XA2, Q5AW24, Q69ZK0, Q7S9J6, Q8TCU6, Q9W0E3, A1IGU3, A1IGU4, A1IGU5, A1ZAY1, E7F1U2, O15068, O15085, O77775, P10569, P15498, P19878, P35991, Q08DN7, Q3LAC4, Q5DU57, Q60992, Q63406, Q70Z35, Q80VK6, Q96N96, Q9NHV9, Q9NXL2, O60229, P40995

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PREX1	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”
PPP1CA	“up-regulates activity”	PREX1	dephosphorylation
AUTS2	“up-regulates activity”	PREX1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PIP3 activates AKT signaling	6	14.8×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of actin cytoskeleton organization	5	22.5×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	187
Likely benign	16
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

8152 predictions. Top by Δscore:

Variant	Effect	Δscore
20:48627855:CCTCA:C	donor_loss	1.0000
20:48627856:CTCA:C	donor_loss	1.0000
20:48627857:TCACC:T	donor_loss	1.0000
20:48627858:CAC:C	donor_loss	1.0000
20:48627859:A:C	donor_loss	1.0000
20:48627860:C:CA	donor_loss	1.0000
20:48627860:CCTG:C	donor_gain	1.0000
20:48627959:TGCTC:T	acceptor_gain	1.0000
20:48627960:GCTC:G	acceptor_gain	1.0000
20:48627961:CTC:C	acceptor_gain	1.0000
20:48627961:CTCC:C	acceptor_gain	1.0000
20:48627962:TC:T	acceptor_gain	1.0000
20:48627962:TCCT:T	acceptor_gain	1.0000
20:48627963:CC:C	acceptor_gain	1.0000
20:48627963:CCTGC:C	acceptor_loss	1.0000
20:48627964:C:CC	acceptor_gain	1.0000
20:48627964:CT:C	acceptor_loss	1.0000
20:48627965:T:A	acceptor_loss	1.0000
20:48627968:A:T	acceptor_gain	1.0000
20:48627970:C:CT	acceptor_gain	1.0000
20:48629445:TCA:T	donor_loss	1.0000
20:48629447:A:AC	donor_gain	1.0000
20:48629447:A:T	donor_loss	1.0000
20:48629448:C:CC	donor_gain	1.0000
20:48629448:C:CG	donor_loss	1.0000
20:48629448:CCT:C	donor_gain	1.0000
20:48629618:TCAG:T	acceptor_gain	1.0000
20:48629619:CAG:C	acceptor_gain	1.0000
20:48629619:CAGC:C	acceptor_gain	1.0000
20:48629620:AG:A	acceptor_gain	1.0000

AlphaMissense

10980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:48676203:A:G	L552P	1.000
20:48679709:A:G	F494S	1.000
20:48679712:C:G	R493P	1.000
20:48679716:A:C	Y492D	1.000
20:48679736:A:G	F485S	1.000
20:48681243:A:T	I476N	1.000
20:48681261:A:G	L470P	1.000
20:48681270:C:T	G467D	1.000
20:48681271:C:G	G467R	1.000
20:48681283:C:G	G463R	1.000
20:48681283:C:T	G463R	1.000
20:48681318:A:G	L451P	1.000
20:48688660:C:T	G444D	1.000
20:48688754:C:A	G413W	1.000
20:48688754:C:G	G413R	1.000
20:48688754:C:T	G413R	1.000
20:48690984:C:A	W383C	1.000
20:48690984:C:G	W383C	1.000
20:48690985:C:G	W383S	1.000
20:48690986:A:G	W383R	1.000
20:48690986:A:T	W383R	1.000
20:48690993:C:A	K380N	1.000
20:48690993:C:G	K380N	1.000
20:48691017:G:C	C372W	1.000
20:48691019:A:G	C372R	1.000
20:48691021:A:T	V371D	1.000
20:48691023:A:C	F370L	1.000
20:48691023:A:T	F370L	1.000
20:48691024:A:C	F370C	1.000
20:48691024:A:G	F370S	1.000

dbSNP variants (sampled 300 via entrez): RS1000024350 (20:48767241 C>G,T), RS1000024529 (20:48691847 C>T), RS1000034260 (20:48772152 C>A), RS1000047844 (20:48643254 A>G), RS1000048751 (20:48866533 A>G), RS1000071343 (20:48764012 C>G,T), RS1000078225 (20:48717487 A>C), RS1000082379 (20:48882435 G>C), RS1000110812 (20:48625904 G>A), RS1000113009 (20:48845012 C>T), RS1000161558 (20:48776789 T>C), RS1000176687 (20:48856998 C>G), RS1000177952 (20:48634252 G>A), RS1000178557 (20:48654271 G>A), RS1000179096 (20:48723887 C>T)

Disease associations

OMIM: gene MIM:606905 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST000107_8	Tonometry	2.000000e-06
GCST001018_2	Nephrotic syndrome (acquired)	3.000000e-06
GCST003017_12	Colorectal cancer	4.000000e-09
GCST004280_74	Diastolic blood pressure	1.000000e-12
GCST004483_8	Multiple myeloma	1.000000e-13
GCST005316_245	Intelligence (MTAG)	8.000000e-12
GCST005316_246	Intelligence (MTAG)	3.000000e-10
GCST005316_249	Intelligence (MTAG)	4.000000e-11
GCST005316_252	Intelligence (MTAG)	2.000000e-11
GCST005316_430	Intelligence (MTAG)	3.000000e-11
GCST006020_21	Diastolic blood pressure	3.000000e-10
GCST006267_3	Response to selective serotonin reuptake inhibitors in depression	3.000000e-06
GCST006269_1118	General cognitive ability	5.000000e-10
GCST006269_1187	General cognitive ability	3.000000e-08
GCST006923_15	Loneliness	3.000000e-08
GCST006924_7	Loneliness (MTAG)	3.000000e-09
GCST007044_24	Extremely high intelligence	7.000000e-10
GCST007094_232	Diastolic blood pressure	2.000000e-11
GCST007552_21	Colorectal cancer	4.000000e-11
GCST007856_84	Colorectal cancer or advanced adenoma	6.000000e-15
GCST008151_32	Waist circumference	4.000000e-06
GCST008160_77	Waist circumference	4.000000e-06
GCST008163_220	Height	3.000000e-07
GCST009869_67	Colorectal cancer	8.000000e-12
GCST010866_168	Coronary artery disease	3.000000e-08
GCST012396_12	Multiple myeloma	2.000000e-06
GCST90002388_581	Lymphocyte count	7.000000e-10
GCST90002389_424	Lymphocyte percentage of white cells	2.000000e-09
GCST90002390_672	Mean corpuscular hemoglobin	4.000000e-18
GCST90002393_460	Monocyte count	3.000000e-10

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004337	intelligence
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007865	loneliness measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0005091	monocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	7
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, affects expression	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases abundance, increases expression	3
Temozolomide	decreases expression, affects response to substance	2
Vorinostat	affects cotreatment, increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenicals	decreases expression	2
Cisplatin	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
sotorasib	decreases expression, affects cotreatment	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
cerous chloride	affects cotreatment, decreases expression	1
lanthanum chloride	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation, increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases 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

Clinical trials (associated diseases)

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