RASGRP1

RAS guanyl releasing protein 1, the group of EF-hand domain containing

Basic information

Region (hg38): 15:38488103-38565575

Links

ENSG00000172575NCBI:10125OMIM:603962HGNC:9878Uniprot:O95267AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • autoimmune lymphoproliferative syndrome (Supportive), mode of inheritance: AD
  • immunodeficiency 64 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Immunodeficiency 64 with lymphoproliferationARAllergy/Immunology/Infectious; OncologicThe condition can involve early-onset recurrent bacterial, viral, and fungal infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals have been increased susceptibility to EBV infection and risk of EBV-associated lymphoma, and awareness may allow prompt diagnosis and managementAllergy/Immunology/Infectious; Oncologic27776107; 28822832; 29155103; 29282224

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RASGRP1 gene.

  • not provided (13 variants)
  • Immunodeficiency 64 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RASGRP1 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
clinvar
100
clinvar
7
clinvar
111
missense
146
clinvar
4
clinvar
1
clinvar
151
nonsense
6
clinvar
2
clinvar
8
start loss
1
clinvar
1
frameshift
7
clinvar
7
inframe indel
2
clinvar
2
splice donor/acceptor (+/-2bp)
1
clinvar
4
clinvar
5
splice region
8
14
1
23
non coding
2
clinvar
51
clinvar
7
clinvar
60
Total 14 4 157 155 15

Highest pathogenic variant AF is 0.00000657

Variants in RASGRP1

This is a list of pathogenic ClinVar variants found in the RASGRP1 region.

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

Position Type Phenotype Significance ClinVar
15-38490554-C-T Likely benign (Dec 06, 2023)1583698
15-38490566-A-G Likely benign (Feb 21, 2022)2143592
15-38490567-C-T Uncertain significance (Jul 12, 2021)1480169
15-38490580-G-A Uncertain significance (Nov 04, 2021)1349434
15-38490591-T-C Uncertain significance (Mar 07, 2021)1514676
15-38490599-T-C Likely benign (Sep 17, 2023)2918515
15-38490608-C-G Uncertain significance (Nov 30, 2021)1415213
15-38490612-A-T Uncertain significance (Oct 19, 2021)1461199
15-38490614-G-A Likely benign (Feb 18, 2023)2795055
15-38490621-A-G Uncertain significance (Nov 07, 2023)1394789
15-38490653-T-C Likely benign (Oct 06, 2021)1645719
15-38490667-C-A Uncertain significance (Jan 31, 2022)2080892
15-38490679-T-A not specified Uncertain significance (Mar 23, 2022)1416599
15-38490688-C-T Uncertain significance (Jul 17, 2023)1996833
15-38490694-G-C Uncertain significance (Jan 28, 2021)1367241
15-38490700-G-A Likely benign (Jan 19, 2024)1640381
15-38490701-G-A Likely benign (Dec 01, 2023)3006142
15-38494393-C-T not specified Uncertain significance (Jun 24, 2022)2296536
15-38494397-G-A Likely benign (Oct 04, 2023)2966828
15-38494403-A-G Likely benign (Jan 27, 2022)1929632
15-38494412-G-C RASGRP1-related disorder Likely benign (Oct 26, 2023)2771966
15-38494419-C-T not specified Uncertain significance (Apr 06, 2024)1399853
15-38494420-G-A Uncertain significance (Aug 16, 2022)2088737
15-38494421-G-A Likely benign (Jun 27, 2022)1624413
15-38494432-T-C Uncertain significance (Jun 10, 2022)1942697

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RASGRP1protein_codingprotein_codingENST00000310803 1777473
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9660.03451246410171246580.0000682
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.742594170.6220.00002135211
Missense in Polyphen59148.050.398511892
Synonymous1.091401570.8890.000008111517
Loss of Function4.95741.30.1690.00000235476

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002910.0000291
Ashkenazi Jewish0.0001990.000199
East Asian0.00005660.0000556
Finnish0.00009390.0000928
European (Non-Finnish)0.00007170.0000708
Middle Eastern0.00005660.0000556
South Asian0.00009830.0000980
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Functions as a calcium- and diacylglycerol (DAG)- regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP (PubMed:15899849, PubMed:23908768). Activates the Erk/MAP kinase cascade (PubMed:15899849). Regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B- lymphocyte antigen receptors to Ras (PubMed:10807788, PubMed:12839994). Regulates NK cell cytotoxicity and ITAM- dependent cytokine production by activation of Ras-mediated ERK and JNK pathways (PubMed:19933860). Functions in mast cell degranulation and cytokine secretion, regulating FcERI-evoked allergic responses (By similarity). May also function in differentiation of other cell types (PubMed:12845332). {ECO:0000250|UniProtKB:Q9Z1S3, ECO:0000269|PubMed:10807788, ECO:0000269|PubMed:12782630, ECO:0000269|PubMed:12839994, ECO:0000269|PubMed:12845332, ECO:0000269|PubMed:15060167, ECO:0000269|PubMed:15184873, ECO:0000269|PubMed:15899849, ECO:0000269|PubMed:19933860, ECO:0000269|PubMed:23908768}.;
Disease
DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17878389}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Aberrantly spliced isoforms and/or diminished levels of RASGRP1 are found in a cohort of SLE patients raising the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients.;
Pathway
Platelet activation - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);T-Cell Receptor and Co-stimulatory Signaling;Vitamin D Receptor Pathway;MAPK Signaling Pathway;Ras Signaling;Serotonin HTR1 Group and FOS Pathway;Serotonin Receptor 2 and ELK-SRF-GATA4 signaling;Signaling by GPCR;Regulation of Ras family activation;Signal Transduction;Activation of RAS in B cells;Signaling by the B Cell Receptor (BCR);CD4 T cell receptor signaling-ERK cascade;Integrin alphaIIb beta3 signaling;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Rap1 signalling;Adaptive Immune System;Downstream signaling events of B Cell Receptor (BCR);Platelet Aggregation (Plug Formation);Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;Integrin signaling;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;FCERI mediated NF-kB activation;G alpha (q) signalling events;GPCR downstream signalling;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

pRec
0.170

Intolerance Scores

loftool
0.775
rvis_EVS
-0.82
rvis_percentile_EVS
11.77

Haploinsufficiency Scores

pHI
0.363
hipred
Y
hipred_score
0.793
ghis
0.576

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.789

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rasgrp1
Phenotype
liver/biliary system phenotype; hematopoietic system phenotype; renal/urinary system phenotype; immune system phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process
MAPK cascade;cytokine production;positive regulation of protein phosphorylation;inflammatory response to antigenic stimulus;signal transduction;Ras protein signal transduction;regulation of phosphatidylinositol 3-kinase signaling;cell differentiation;secretory granule localization;positive regulation of granulocyte macrophage colony-stimulating factor production;positive regulation of tumor necrosis factor production;positive regulation of natural killer cell differentiation;positive regulation of T cell differentiation in thymus;mast cell degranulation;positive regulation of MAP kinase activity;positive regulation of GTPase activity;positive regulation of natural killer cell mediated cytotoxicity;positive regulation of JNK cascade;positive regulation of Ras protein signal transduction;vesicle transport along microtubule;protein complex oligomerization;regulation of ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;activation of GTPase activity;regulation of phospholipase C activity;regulation of p38MAPK cascade;positive regulation of interferon-gamma secretion
Cellular component
Golgi membrane;endoplasmic reticulum membrane;Golgi apparatus;cytosol;plasma membrane;membrane;mast cell granule
Molecular function
phosphatidylserine binding;guanyl-nucleotide exchange factor activity;Ras guanyl-nucleotide exchange factor activity;GTPase activator activity;calcium ion binding;zinc ion binding;lipid binding;diacylglycerol binding;phosphatidylcholine binding;protein homodimerization activity