RASGRP1 RAS guanyl releasing protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RASGRP1provided by HGNC
Official Full Name: RAS guanyl releasing protein 1provided by HGNC
Primary source: HGNC:HGNC:9878
See related: Ensembl:ENSG00000172575 MIM:603962; AllianceGenome:HGNC:9878
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IMD64; RASGRP; CALDAG-GEFI; CALDAG-GEFII
Summary: This gene is a member of a family of genes characterized by the presence of a Ras superfamily guanine nucleotide exchange factor (GEF) domain. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cells and B-cells development, homeostasis and differentiation. Alternatively spliced transcript variants encoding different isoforms have been identified. Altered expression of the different isoforms of this protein may be a cause of susceptibility to systemic lupus erythematosus (SLE). [provided by RefSeq, Jul 2008]
Expression: Broad expression in lymph node (RPKM 12.0), brain (RPKM 10.5) and 15 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q14

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (38488103..38564814, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (36293389..36370106, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (38780304..38857015, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.
Title: A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.
Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients.
Title: Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients.
Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.
Title: Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.
Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity.
Title: Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity.
Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation.
Title: Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation.
RasGRP1 is a potential biomarker to stratify anti-EGFR therapy response in colorectal cancer.
Title: RasGRP1 is a potential biomarker to stratify anti-EGFR therapy response in colorectal cancer.
Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility.
Title: Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility.
The expression of VEGF, RasGRP1, and AKT phosphorylation was downregulated in HUVECs exposed to high glucose compared with normal glucose, whereas metformin upregulated the RasGRP1-dependent VEGF signaling and ameliorates the impaired angiogenesis caused by high glucose. RasGRP1 is involved in the VEGF-induced angiogenesis and the pro-angiogenesis effects of metformin under hyperglycemia.
Title: RasGRP1 is a target for VEGF to induce angiogenesis and involved in the endothelial-protective effects of metformin under high glucose in HUVECs.
RASGRP1 deficiency is associated with life-threatening immune dysregulation, severe autoimmune manifestations, and susceptibility to EBV-induced B cell malignancies. Early diagnosis is critical and hematopoietic stem cell transplantation might be considered as curative treatment.
Title: Novel Mutations in RASGRP1 are Associated with Immunodeficiency, Immune Dysregulation, and EBV-Induced Lymphoma.
this study shows that RASGRP1 mutation should be considered in patients with autoimmune lymphoproliferative syndrome-like disease
Title: RASGRP1 mutation in autoimmune lymphoproliferative syndrome-like disease.

Submit: New GeneRIF Correction See all GeneRIFs (44)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Immunodeficiency 64 MedGen: C5231402 OMIM: 618534 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of atypical psychosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH123035 (e-PCR)
- UniSTS:135424

RH68073 (e-PCR)
- UniSTS:25374

D15S732E (e-PCR)
- UniSTS:151626

WI-22267 (e-PCR)
- UniSTS:53330

SHGC-149041 (e-PCR)
- UniSTS:176759

SHGC-64063 (e-PCR)
- UniSTS:43918

RH99024 (e-PCR)
- UniSTS:89028

SHGC-36087 (e-PCR)
- UniSTS:63453

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables diacylglycerol binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables lipid binding	TAS Traceable Author Statement more info	PubMed
enables phosphatidylcholine binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables zinc ion binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in Ras protein signal transduction	TAS Traceable Author Statement more info
involved_in T cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in activation of GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
involved_in mast cell degranulation	IEA Inferred from Electronic Annotation more info
involved_in natural killer cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of MAP kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of Ras protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell differentiation in thymus	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of granulocyte macrophage colony-stimulating factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of natural killer cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of natural killer cell mediated cytotoxicity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of type II interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
NOT involved_in regulation of p38MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
NOT involved_in regulation of phospholipase C activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in secretory granule localization	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in vesicle transport along microtubule	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: RAS guanyl-releasing protein 1

Names: RAS guanyl nucleotide-releasing protein 1; RAS guanyl releasing protein 1 (calcium and DAG-regulated); calcium and DAG-regulated guanine nucleotide exchange factor II; calcium- and diacylglycerol-regulated guanine nucleotide exchange factor II; guanine nucleotide exchange factor, calcium- and DAG-regulated, Rap1A; ras activator RasGRP

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023268.2 RefSeqGene

Range

4993..81704

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001128602.2 → NP_001122074.1 RAS guanyl-releasing protein 1 isoform b

See identical proteins and their annotated locations for NP_001122074.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as variant A, lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (b), that is missing an internal segment compared to isoform a.

Source sequence(s)

AA742351, AC124306, AF081195, AK314091, BC109296, BU431038, DA993002

Consensus CDS

CCDS45221.1

UniProtKB/TrEMBL

B2RA89

Related

ENSP00000388540.2, ENST00000450598.6

Conserved Domains (4) summary

smart00147
Location:201 → 437

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

smart00229
Location:54 → 175

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

pfam00130
Location:507 → 556

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

pfam13499
Location:443 → 492

EF-hand_7; EF-hand domain pair
NM_001306086.2 → NP_001293015.1 RAS guanyl-releasing protein 1 isoform c

See identical proteins and their annotated locations for NP_001293015.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two internal exons one of which results in a frameshift compared to variant 1. The encoded protein (isoform c) is shorter and has a distinct C-terminus compared to isoform a.

Source sequence(s)

AC116158, AC124306, AY858556, DA993002

Consensus CDS

CCDS76733.1

UniProtKB/Swiss-Prot

O95267

Related

ENSP00000452721.1, ENST00000559830.5

Conserved Domains (4) summary

smart00147
Location:201 → 437

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

smart00229
Location:54 → 175

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

pfam00130
Location:507 → 556

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

pfam13499
Location:443 → 492

EF-hand_7; EF-hand domain pair
NM_005739.4 → NP_005730.2 RAS guanyl-releasing protein 1 isoform a

See identical proteins and their annotated locations for NP_005730.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript, and encodes the longer isoform (a).

Source sequence(s)

AA742351, AC124306, AF081195, AK314091, BC109296, BU431038, DA993002

Consensus CDS

CCDS45222.1

UniProtKB/Swiss-Prot

O95267, Q56CZ0, Q58G75, Q59HB1, Q5I3A8, Q6GV31, Q6NX39, Q7LDG6, Q9UI94, Q9UNN9

UniProtKB/TrEMBL

B2RA89

Related

ENSP00000310244.5, ENST00000310803.10

Conserved Domains (5) summary

smart00147
Location:201 → 437

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

smart00229
Location:54 → 175

RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif

pfam00130
Location:542 → 591

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

pfam13499
Location:478 → 527

EF-hand_7; EF-hand domain pair

cl21462
Location:734 → 780

bZIP; Basic leucine zipper (bZIP) domain of bZIP transcription factors: a DNA-binding and dimerization domain