RASGRF2

Ras protein specific guanine nucleotide releasing factor 2, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Basic information

Region (hg38): 5:80960362-81230162

Links

ENSG00000113319 ∙ NCBI:5924 ∙ OMIM:606614 ∙ HGNC:9876 ∙ Uniprot:O14827 ∙ 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 RASGRF2 gene.

• Inborn genetic diseases (36 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RASGRF2 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						0
missense			34	2		36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	34	2	0

Variants in RASGRF2

This is a list of pathogenic ClinVar variants found in the RASGRF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-80960751-G-C		not specified	Uncertain significance (Aug 22, 2023)
5-80960771-C-G		not specified	Uncertain significance (Feb 11, 2022)
5-80960844-G-C		not specified	Uncertain significance (Aug 17, 2021)
5-80960920-G-A		not specified	Uncertain significance (Mar 01, 2024)
5-81068159-A-G		not specified	Uncertain significance (Oct 10, 2023)
5-81070492-A-G		not specified	Uncertain significance (Oct 12, 2021)
5-81070498-G-A		not specified	Uncertain significance (Sep 14, 2023)
5-81070506-T-A		not specified	Uncertain significance (Nov 09, 2023)
5-81073244-A-T		not specified	Uncertain significance (Aug 02, 2023)
5-81073286-A-C		not specified	Uncertain significance (Aug 28, 2023)
5-81073377-G-A		not specified	Uncertain significance (Sep 01, 2021)
5-81080117-A-G			Benign (Jul 06, 2018)
5-81080691-C-G		not specified	Uncertain significance (Aug 10, 2023)
5-81085851-A-G		not specified	Uncertain significance (Jul 06, 2022)
5-81085865-A-G		not specified	Uncertain significance (Apr 17, 2023)
5-81085907-T-C		not specified	Uncertain significance (Aug 01, 2023)
5-81086948-G-T		not specified	Uncertain significance (Mar 02, 2023)
5-81092897-T-G		not specified	Uncertain significance (Feb 28, 2024)
5-81094871-A-G		not specified	Uncertain significance (Aug 28, 2023)
5-81094958-A-G		not specified	Uncertain significance (Sep 14, 2023)
5-81109069-A-G		not specified	Uncertain significance (Jul 19, 2023)
5-81112621-G-A		not specified	Uncertain significance (May 24, 2023)
5-81112821-G-A		not specified	Uncertain significance (Apr 18, 2023)
5-81112836-C-A		not specified	Uncertain significance (Sep 21, 2021)
5-81113591-T-C		not specified	Uncertain significance (Jan 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RASGRF2	protein_coding	protein_coding	ENST00000265080	27	269485

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.152	0.848	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.03	480	707	0.679	0.0000395	8160
Missense in Polyphen		141	260.04	0.54222		3094
Synonymous	1.13	245	269	0.912	0.0000163	2354
Loss of Function	5.81	16	67.5	0.237	0.00000382	758

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000111	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000124	0.000114
Middle Eastern	0.000111	0.000109
South Asian	0.000294	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:15128856}.
• Pathway: Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);MAPK Signaling Pathway;Ras Signaling;Signaling by GPCR;Regulation of Ras family activation;Signal Transduction;Rho GTPase cycle;Neuronal System;Signaling by Rho GTPases;Regulation of RAC1 activity;NRAGE signals death through JNK;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;G alpha (12/13) signalling events;Ras activation upon Ca2+ influx through NMDA receptor;CREB phosphorylation through the activation of Ras;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;GPCR downstream signalling;Cell death signalling via NRAGE, NRIF and NADE (Consensus)

Intolerance Scores

• loftool: 0.624
• rvis_EVS: -1.26
• rvis_percentile_EVS: 5.34

Haploinsufficiency Scores

• pHI: 0.197
• hipred: Y
• hipred_score: 0.671
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.716

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rasgrf2
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; 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); hematopoietic system phenotype; normal phenotype

Gene ontology

• Biological process: MAPK cascade;G protein-coupled receptor signaling pathway;small GTPase mediated signal transduction;response to endoplasmic reticulum stress;regulation of Rho protein signal transduction;positive regulation of apoptotic process;regulation of small GTPase mediated signal transduction
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;plasma membrane
• Molecular function: guanyl-nucleotide exchange factor activity;Ras guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;calmodulin binding