PREX2

phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2, the group of Dbl family Rho GEFs|Protein phosphatase 1 regulatory subunits|PDZ domain containing

Basic information

Region (hg38): 8:67952045-68237032

Previous symbols: [ "DEPDC2" ]

Links

ENSG00000046889 ∙ NCBI:80243 ∙ OMIM:612139 ∙ HGNC:22950 ∙ Uniprot:Q70Z35 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PREX2 gene.

• Inborn genetic diseases (41 variants)
• not provided (20 variants)
• not specified (2 variants)
• PREX2-related condition (1 variants)
• Cerebral arteriovenous malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PREX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	6	10
missense		1	44	2	1	48
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					3	3
non coding				1		1
Total	0	1	45	7	7

Highest pathogenic variant AF is 0.00000658

Variants in PREX2

This is a list of pathogenic ClinVar variants found in the PREX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-67952391-G-C		PREX2-related disorder	Benign/Likely benign (Nov 01, 2022)
8-67952410-C-G		not specified	Uncertain significance (Jan 02, 2024)
8-67952411-G-T		not specified	Uncertain significance (Jan 09, 2024)
8-67952490-G-A		PREX2-related disorder	Benign (Mar 06, 2019)
8-67952493-G-A		PREX2-related disorder	Benign (Oct 18, 2019)
8-67952516-C-T		not specified	Uncertain significance (Jun 05, 2023)
8-68015357-C-T		Lip and oral cavity carcinoma	association (Nov 02, 2015)
8-68017871-G-A		PREX2-related disorder	Likely benign (Aug 14, 2019)
8-68017892-A-G		not specified	Uncertain significance (Oct 06, 2021)
8-68019605-C-T		PREX2-related disorder	Likely benign (Jun 27, 2019)
8-68019606-G-A		not specified	Uncertain significance (Jun 22, 2023)
8-68022056-T-A			not provided (-)
8-68022107-C-T		PREX2-related disorder	Likely benign (Dec 06, 2019)
8-68022127-G-A		not specified	Uncertain significance (Mar 17, 2016)
8-68027289-T-C		not specified	Uncertain significance (Sep 21, 2021)
8-68030589-C-T			Benign/Likely benign (Aug 01, 2022)
8-68030641-C-T		not specified	Uncertain significance (Dec 14, 2023)
8-68030666-C-T		PREX2-related disorder	Benign (Apr 11, 2019)
8-68044537-G-A		not specified	Uncertain significance (Jul 13, 2021)
8-68044555-A-G		not specified	Uncertain significance (Jun 06, 2022)
8-68044581-G-A		PREX2-related disorder	Likely benign (Jul 22, 2023)
8-68053107-T-C		PREX2-related disorder	Likely benign (Jun 04, 2019)
8-68055823-T-C		PREX2-related disorder	Benign (Dec 31, 2019)
8-68055838-T-G		not specified	Uncertain significance (Jan 19, 2022)
8-68055931-C-A		PREX2-related disorder	Benign (Oct 17, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PREX2	protein_coding	protein_coding	ENST00000288368	40	284913

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.33e-16	1.00	125531	1	216	125748	0.000863

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.73	719	862	0.834	0.0000454	10632
Missense in Polyphen		300	376.21	0.79742		4618
Synonymous	-0.344	307	299	1.03	0.0000157	2884
Loss of Function	4.57	41	87.0	0.471	0.00000403	1134

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00376	0.00375
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.000222	0.000217
Finnish	0.00327	0.00319
European (Non-Finnish)	0.000365	0.000360
Middle Eastern	0.000222	0.000217
South Asian	0.000393	0.000392
Other	0.00117	0.00114

dbNSFP

Source: dbNSFP

• Function: 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 heterotrimeric G protein. Mediates the activation of RAC1 in a PI3K-dependent manner. May be an important mediator of Rac signaling, acting directly downstream of both G protein- coupled receptors and phosphoinositide 3-kinase. {ECO:0000269|PubMed:15304342, ECO:0000269|PubMed:15304343, ECO:0000269|PubMed:15897194}.
• Pathway: Signal Transduction;Regulation of PTEN stability and activity;Regulation of RAC1 activity;PTEN Regulation;PIP3 activates AKT signaling;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.582
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.42

Haploinsufficiency Scores

• pHI: 0.347
• hipred: Y
• hipred_score: 0.706
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.186

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prex2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;adult locomotory behavior;phosphatidylinositol 3-kinase signaling;regulation of Rho protein signal transduction;positive regulation of GTPase activity;dendrite morphogenesis
• Cellular component: cytosol;plasma membrane
• Molecular function: GTPase activator activity;Rac guanyl-nucleotide exchange factor activity