PREX2 (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2)

Gene

• Entrez ID: 80243
• Gene name: Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2
• Gene symbol: PREX2
• Synonyms (NCBI Gene): DEP.2, DEPDC2, P-REX2, PPP1R129
• Chromosome: 8
• Chromosome location: 8q13.2
• Summary: The protein encoded by this gene belongs to the phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger (PREX) family, which are Dbl-type guanine-nucleotide exchange factors for Rac family small G proteins. Structural domains of this prote

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs778089198	G>A	Likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018971	hsa-miR-335-5p	Microarray	18185580
MIRT053064	hsa-miR-338-3p	Immunofluorescence, Microarray, Western blot	24140344
MIRT053064	hsa-miR-338-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	24375644
MIRT639642	hsa-miR-4768-3p	HITS-CLIP	23824327
MIRT639641	hsa-miR-4459	HITS-CLIP	23824327
MIRT639640	hsa-miR-4433a-3p	HITS-CLIP	23824327
MIRT639639	hsa-miR-6849-3p	HITS-CLIP	23824327
MIRT639638	hsa-miR-3190-5p	HITS-CLIP	23824327
MIRT639637	hsa-miR-219b-5p	HITS-CLIP	23824327
MIRT639636	hsa-miR-3926	HITS-CLIP	23824327
MIRT639635	hsa-miR-548s	HITS-CLIP	23824327
MIRT639642	hsa-miR-4768-3p	HITS-CLIP	23824327
MIRT639641	hsa-miR-4459	HITS-CLIP	23824327
MIRT639640	hsa-miR-4433a-3p	HITS-CLIP	23824327
MIRT639639	hsa-miR-6849-3p	HITS-CLIP	23824327
MIRT639638	hsa-miR-3190-5p	HITS-CLIP	23824327
MIRT639637	hsa-miR-219b-5p	HITS-CLIP	23824327
MIRT639636	hsa-miR-3926	HITS-CLIP	23824327
MIRT639635	hsa-miR-548s	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IBA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	15304343
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS
GO:0005096	Function	GTPase activator activity	IBA
GO:0005096	Function	GTPase activator activity	IDA	15304343
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IBA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IDA	15304343
GO:0008344	Process	Adult locomotory behavior	IEA
GO:0030291	Function	Protein serine/threonine kinase inhibitor activity	IBA
GO:0032007	Process	Negative regulation of TOR signaling	IBA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0043491	Process	Phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA
GO:0048813	Process	Dendrite morphogenesis	IEA
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	IEA
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS

Other IDs

• MIM: 612139
• HGNC: 22950
• e!Ensembl: ENSG00000046889

Protein

• UniProt ID: Q70Z35
• Protein name: Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein (P-Rex2) (PtdIns(3,4,5)-dependent Rac exchanger 2) (DEP domain-containing protein 2)
• Protein function: Functions as a RAC1 guanine nucleotide exchange factor (GEF), activating 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 hete
• PDB: 6BNM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00621	RhoGEF	27 → 212	RhoGEF domain	Domain
  PF00169	PH	246 → 359	PH domain	Domain
  PF00610	DEP	393 → 462	Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)	Domain
  PF00610	DEP	495 → 563	Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Isoform 1 is highly expressed in skeletal muscle, heart and placenta, absent from peripheral blood leukocytes. Isoform 2 is expressed in skeletal muscle, kidney, small intestine, and placenta. Isoform 3 is expressed in the heart. {ECO:
• Sequence:

  MSEDSRGDSRAESAKDLEKQLRLRVCVLSELQKTERDYVGTLEFLVSAFLHRMNQCAASK
  VDKNVTEETVKMLFSNIEDILAVHKEFLKVVEECLHPEPNAQQEVGTCFLHFKDKFRIYD
  EYCSNHEKAQKLLLELNKIRTIRTFLLNCMLLGGRKNTDVPLEGYLVTPIQRICKYPLIL
  KELLKRTPRKHSDYAAVMEALQAMKAVCSNINEAKRQMEKLEVLEEWQSHIEGWEGSNIT
  DTCTEMLMCGVLLKISSGNIQERVFFLFDNLLVYCKRKHRRLKNSKASTDGHRYLFRGRI
  NTEVMEVENVDDGTADFHSSGHIVVNGWKIHNTAKNKWFVCMAKTPEEKHEWFEAILKER
  ERRKGLKLGMEQDTWVMISEQGEKLYKMMCRQGNLIKDRKRKLTTFPKCFLGSEFVSWLL
  EIGEIHRPEEGVHLGQALLENGIIHHVTDKHQFKPEQMLYRFRYDDGTFYPRNEMQDVIS
  KGVRLYCRLHSLFTPVIRDKDYHLRTYKSVVMANKLIDWLIAQGDCRTREEAMIFGVGLC
  DNGFMHHVLEKSEFKDEPLLFRFFSDEEMEGSNMKHRLMKHDLKVVENVIAKSLLIKSNE
  GSYGFGLEDKNKVPIIKLVEKGSNAEMAGMEVGKKIFAINGDLVFMRPFNEVDCFLKSCL
  NSRKPLRVLVSTKPRETVKIPDSADGLGFQIRGFGPSVVHAVGRGTVAAAAGLHPGQCII
  KVNGINVSKETHASVIAHVTACRKYRRPTKQDSIQWVYNSIESAQEDLQKSHSKPPGDEA
  GDAFDCKVEEVIDKFNTMAIIDGKKEHVSLTVDNVHLEYGVVYEYDSTAGIKCNVVEKMI
  EPKGFFSLTAKILEALAKSDEHFVQNCTSLNSLNEVIPTDLQSKFSALCSERIEHLCQRI
  SSYKKFSRVLKNRAWPTFKQAKSKISPLHSSDFCPTNCHVNVMEVSYPKTSTSLGSAFGV
  QLDSRKHNSHDKENKSSEQGKLSPMVYIQHTITTMAAPSGLSLGQQDGHGLRYLLKEEDL
  ETQDIYQKLLGKLQTALKEVEMCVCQIDDLLSSITYSPKLERKTSEGIIPTDSDNEKGER
  NSKRVCFNVAGDEQEDSGHDTISNRDSYSDCNSNRNSIASFTSICSSQCSSYFHSDEMDS
  GDELPLSVRISHDKQDKIHSCLEHLFSQVDSITNLLKGQAVVRAFDQTKYLTPGRGLQEF
  QQEMEPKLSCPKRLRLHIKQDPWNLPSSVRTLAQNIRKFVEEVKCRLLLALLEYSDSETQ
  LRRDMVFCQTLVATVCAFSEQLMAALNQMFDNSKENEMETWEASRRWLDQIANAGVLFHF
  QSLLSPNLTDEQAMLEDTLVALFDLEKVSFYFKPSEEEPLVANVPLTYQAEGSRQALKVY
  FYIDSYHFEQLPQRLKNGGGFKIHPVLFAQALESMEGYYYRDNVSVEEFQAQINAASLEK
  VKQYNQKLRAFYLDKSNSPPNSTSKAAYVDKLMRPLNALDELYRLVASFIRSKRTAACAN
  TACSASGVGLLSVSSELCNRLGACHIIMCSSGVHRCTLSVTLEQAIILARSHGLPPRYIM
  QATDVMRKQGARVQNTAKNLGVRDRTPQSAPRLYKLCEPPPPAGEE

• Sequence length: 1606

Pathways

Reactome:

Regulation of PTEN stability and activity

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cerebral arteriovenous malformation	Likely pathogenic	rs778089198	RCV000656333	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ARTERIOVENOUS MALFORMATIONS, CEREBRAL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BLADDER EXSTROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DRY EYE SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lip and oral cavity carcinoma	association	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCREATIC CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PREX2-related disorder	Benign; Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	35627223	Associate	★☆☆☆☆ Found in Text Mining only
Bladder Exstrophy	Bladder Exstrophy	GWASCAT_DG	25763902		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	22622578, 28710285		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	22622578, 36404592	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Basal Cell	Basal cell carcinoma	Pubtator	33928395	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	30796242	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Cutaneous Melanoma	Melanoma	BEFREE	26884185		★☆☆☆☆ Found in Text Mining only
Febrile Convulsions	Febrile seizures	BEFREE	23773973		★☆☆☆☆ Found in Text Mining only
Gastritis	Gastritis	Pubtator	34705970	Stimulate	★☆☆☆☆ Found in Text Mining only
Generalized Epilepsy With Febrile Seizures Plus Type 1	Generalized epilepsy with febrile seizures plus	Pubtator	23773973	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	25331116	Associate	★☆☆☆☆ Found in Text Mining only
Lip and Oral Cavity Carcinoma	Lip and Oral Cavity Carcinoma	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Liver carcinoma	Liver carcinoma	BEFREE	25151370, 28205209, 30796242, 31582017, 31776854		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	22622578, 28710285		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	25151370		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25829446, 28710285		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	22622578, 23753921, 25490935, 26884185, 28710285, 30796242		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	22622578, 25490935, 28356599, 30796242, 31647501	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	22622578, 25490935, 26884185, 28100394, 28205209, 28710285		★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	26884185		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	35860812	Associate	★☆☆☆☆ Found in Text Mining only
Seizures Febrile	Seizures	Pubtator	23773973	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	31312661, 34705970	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	34944094, 38305604	Associate	★☆☆☆☆ Found in Text Mining only