RAC2

Rac family small GTPase 2, the group of Rho family GTPases|Receptor ligands

Basic information

Region (hg38): 22:37225269-37259594

Links

ENSG00000128340 ∙ NCBI:5880 ∙ OMIM:602049 ∙ HGNC:9802 ∙ Uniprot:P15153 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neutrophil immunodeficiency syndrome (Supportive), mode of inheritance: Unknown
• neutrophil immunodeficiency syndrome (Strong), mode of inheritance: AD
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia (Strong), mode of inheritance: AR
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia (Limited), mode of inheritance: AR
• neutrophil immunodeficiency syndrome (Moderate), mode of inheritance: AD
• immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia (Definitive), mode of inheritance: AD
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia (Moderate), mode of inheritance: AR
• immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia (Strong), mode of inheritance: AD
• neutrophil immunodeficiency syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 73A with defective neutrophil chemotaxis and leukocytosis; Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopenia; Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinemia	AD/AR	Allergy/Immunology/Infectious; Endocrine	Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial (neutrophil infusions have been described in Immunodeficiency 73A with defective neutrophil chemotaxis and leukocytosis) In Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopenia, HSCT has been described; Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinemia has been described as involving endocrine manifestations (eg, hypothyroidism, hyperparathyroidism), and awareness may allow early diagnosis and management	Allergy/Immunology/Infectious; Endocrine; Renal	10758162; 10961859; 21167572; 25512081; 30654050; 30723080; 31071452; 31382036; 32542921
Renal transplant has been described in Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinemia

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAC2 gene.

• Neutrophil immunodeficiency syndrome (119 variants)
• not specified (11 variants)
• not provided (9 variants)
• Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia (6 variants)
• Immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia (4 variants)
• Inborn genetic diseases (3 variants)
• 6 conditions (1 variants)
• Neutrophil immunodeficiency syndrome;Immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia;Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAC2 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				37	4	41
missense	1	2	40	1		44
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	4		7
non coding				25	7	32
Total	1	2	41	63	11

Variants in RAC2

This is a list of pathogenic ClinVar variants found in the RAC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-37226673-C-T		Neutrophil immunodeficiency syndrome	Likely benign (Nov 27, 2023)
22-37226678-G-A		Neutrophil immunodeficiency syndrome	Uncertain significance (Oct 24, 2022)
22-37226681-G-A		Neutrophil immunodeficiency syndrome	Uncertain significance (Jul 12, 2023)
22-37226683-C-G		Neutrophil immunodeficiency syndrome	Uncertain significance (Sep 17, 2023)
22-37226685-G-A		Neutrophil immunodeficiency syndrome	Likely benign (Nov 28, 2023)
22-37226690-C-T		Neutrophil immunodeficiency syndrome	Conflicting classifications of pathogenicity (Oct 05, 2023)
22-37226691-G-A		Neutrophil immunodeficiency syndrome	Likely benign (Feb 16, 2023)
22-37226692-C-T		Neutrophil immunodeficiency syndrome	Uncertain significance (Sep 06, 2023)
22-37226693-G-A		Neutrophil immunodeficiency syndrome	Uncertain significance (Nov 16, 2023)
22-37226704-C-T		Neutrophil immunodeficiency syndrome	Uncertain significance (Jun 05, 2022)
22-37226705-G-A		Neutrophil immunodeficiency syndrome	Uncertain significance (Aug 08, 2022)
22-37226705-G-T		Neutrophil immunodeficiency syndrome	Likely benign (Mar 26, 2023)
22-37226706-C-T		Neutrophil immunodeficiency syndrome	Likely benign (Oct 13, 2023)
22-37226707-G-A		Neutrophil immunodeficiency syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 13, 2023)
22-37226708-T-C		Neutrophil immunodeficiency syndrome	Uncertain significance (May 23, 2023)
22-37226724-C-T		Neutrophil immunodeficiency syndrome	Likely benign (Nov 21, 2021)
22-37226727-G-A		Neutrophil immunodeficiency syndrome	Likely benign (May 28, 2023)
22-37226727-G-C		Neutrophil immunodeficiency syndrome	Likely benign (Aug 17, 2023)
22-37226730-C-T		Neutrophil immunodeficiency syndrome	Likely benign (Jun 07, 2022)
22-37226731-C-T		Neutrophil immunodeficiency syndrome	Uncertain significance (Oct 30, 2023)
22-37226732-G-A		Neutrophil immunodeficiency syndrome	Uncertain significance (Dec 15, 2022)
22-37226732-G-T		Neutrophil immunodeficiency syndrome	Likely benign (Mar 10, 2022)
22-37226735-T-G		Neutrophil immunodeficiency syndrome	Uncertain significance (Aug 16, 2022)
22-37226741-C-T		Neutrophil immunodeficiency syndrome	Uncertain significance (Sep 07, 2022)
22-37226742-G-A		Neutrophil immunodeficiency syndrome	Likely benign (Dec 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAC2	protein_coding	protein_coding	ENST00000249071	6	19188

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.966	0.0337	125738	0	1	125739	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	42	123	0.342	0.00000863	1233
Missense in Polyphen		8	46.87	0.17068		486
Synonymous	-0.448	55	50.9	1.08	0.00000366	387
Loss of Function	3.01	0	10.5	0.00	4.54e-7	126

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase. {ECO:0000269|PubMed:1660188}.
• Disease: DISEASE: Neutrophil immunodeficiency syndrome (NEUID) [MIM:608203]: An immunodeficiency syndrome due to defective neutrophils. Affected individuals present with leukocytosis, neutrophilia, severe recurrent bacterial infections and poor wound healing. {ECO:0000269|PubMed:10758162}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Focal adhesion - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Adherens junction - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;cAMP signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Bisphosphonate Pathway, Pharmacodynamics;EGF-Core;Integrin-mediated Cell Adhesion;RalA downstream regulated genes;B Cell Receptor Signaling Pathway;Focal Adhesion;MAPK Signaling Pathway;Chemokine signaling pathway;Macrophage markers;Microglia Pathogen Phagocytosis Pathway;Macrophage markers;Chromosomal and microsatellite instability in colorectal cancer;Ras Signaling;Insulin Signaling;Regulation of Actin Cytoskeleton;DNA Damage Response (only ATM dependent);Signaling by GPCR;Signaling by WNT;Signal Transduction;HGF;Rho GTPase cycle;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;RHO GTPases Activate NADPH Oxidases;RHO GTPase Effectors;Signaling by Rho GTPases;PCP/CE pathway;Beta-catenin independent WNT signaling;Hemostasis;G alpha (12/13) signalling events;GPCR downstream signalling;IL8- and CXCR2-mediated signaling events;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.559

Intolerance Scores

• loftool: 0.173
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

• pHI: 0.941
• hipred: Y
• hipred_score: 0.793
• ghis: 0.649

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rac2
• Phenotype: immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: rac2
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: chemotaxis;actin filament organization;signal transduction;G protein-coupled receptor signaling pathway;Rho protein signal transduction;motor neuron axon guidance;positive regulation of cell population proliferation;regulation of hydrogen peroxide metabolic process;positive regulation of lamellipodium assembly;regulation of cell-substrate adhesion;cell migration;Rac protein signal transduction;cell projection assembly;actin cytoskeleton organization;regulation of T cell proliferation;regulation of mast cell degranulation;bone resorption;regulation of protein kinase activity;phosphatidylinositol phosphorylation;regulation of small GTPase mediated signal transduction;positive regulation of protein kinase B signaling;regulation of respiratory burst;regulation of mast cell chemotaxis;lymphocyte aggregation;positive regulation of neutrophil chemotaxis;regulation of neutrophil migration;positive regulation of protein targeting to mitochondrion
• Cellular component: nuclear envelope;cytoplasm;cytosol;actin filament;plasma membrane;focal adhesion;lamellipodium;phagocytic vesicle membrane;cytoplasmic vesicle;cell projection;extracellular exosome
• Molecular function: GTPase activity;protein binding;GTP binding;protein kinase regulator activity;protein kinase binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity