RAPGEF1

Rap guanine nucleotide exchange factor 1

Basic information

Region (hg38): 9:131576769-131740076

Previous symbols: [ "GRF2" ]

Links

ENSG00000107263 ∙ NCBI:2889 ∙ OMIM:600303 ∙ HGNC:4568 ∙ Uniprot:Q13905 ∙ 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 RAPGEF1 gene.

• Inborn genetic diseases (32 variants)
• not provided (6 variants)
• Monoclonal B-Cell Lymphocytosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAPGEF1 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					2	2
missense			33	2		35
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	33	2	3

Variants in RAPGEF1

This is a list of pathogenic ClinVar variants found in the RAPGEF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-131578589-G-A			Benign (Feb 25, 2021)
9-131579513-C-T		not specified	Uncertain significance (Mar 22, 2023)
9-131582623-G-A		not specified	Uncertain significance (Jan 27, 2022)
9-131584333-T-C		not specified	Uncertain significance (Feb 28, 2024)
9-131584333-T-G		not specified	Uncertain significance (Mar 01, 2023)
9-131584579-A-G			Uncertain significance (Jan 01, 2023)
9-131584580-T-C		not specified	Uncertain significance (May 25, 2022)
9-131587996-A-C		not specified	Uncertain significance (Jun 24, 2022)
9-131588024-G-A		not specified	Uncertain significance (Jun 29, 2022)
9-131588026-C-A		not specified	Uncertain significance (Feb 28, 2024)
9-131588814-C-G		not specified	Uncertain significance (Oct 05, 2022)
9-131588921-T-C		not specified	Likely benign (Dec 21, 2022)
9-131588921-T-G		not specified	Uncertain significance (Jul 08, 2022)
9-131592125-C-G		not specified	Uncertain significance (May 31, 2023)
9-131592175-A-C		not specified	Uncertain significance (Nov 01, 2022)
9-131596338-C-T			Benign (Jul 30, 2018)
9-131596360-G-A		not specified	Uncertain significance (Dec 15, 2021)
9-131598270-C-T		not specified	Uncertain significance (Jan 19, 2024)
9-131598281-G-A		not specified	Uncertain significance (Nov 18, 2023)
9-131598297-G-C		not specified	Uncertain significance (Apr 21, 2022)
9-131602095-C-T		not specified	Uncertain significance (Sep 14, 2023)
9-131621830-G-A		not specified	Uncertain significance (Oct 25, 2022)
9-131621833-G-C		not specified	Uncertain significance (Feb 28, 2024)
9-131621846-C-T		not specified	Uncertain significance (Jun 07, 2023)
9-131621948-T-C		not specified	Uncertain significance (May 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAPGEF1	protein_coding	protein_coding	ENST00000372190	24	163305

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000461	124642	0	21	124663	0.0000842

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.13	431	657	0.656	0.0000401	7118
Missense in Polyphen		133	272.8	0.48754		2900
Synonymous	0.822	267	285	0.938	0.0000197	2179
Loss of Function	6.28	7	59.1	0.118	0.00000320	654

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000130	0.000129
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000929	0.0000928
European (Non-Finnish)	0.000142	0.000142
Middle Eastern	0.0000556	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. {ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:7806500}.
• Pathway: Focal adhesion - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Integrin-mediated Cell Adhesion;Androgen Receptor Network in Prostate Cancer;B Cell Receptor Signaling Pathway;IL-3 Signaling Pathway;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;MET in type 1 papillary renal cell carcinoma;Insulin Signaling;Interferon type I signaling pathways;Signal Transduction;Signaling by Interleukins;integrin signaling pathway;Cytokine Signaling in Immune system;GPCR Adenosine A2A receptor;Signaling by PDGF;HGF;TCR;Immune System;MET activates RAP1 and RAC1;BCR;GPCR signaling-G alpha s PKA and ERK;Frs2-mediated activation;Prolonged ERK activation events;Signalling to ERKs;Signaling by NTRK1 (TRKA);Integrin;Signaling by NTRKs;Downstream signal transduction;IFN-gamma pathway;EPO signaling pathway;IL5;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Insulin Pathway;Nectin adhesion pathway;Neurotrophic factor-mediated Trk receptor signaling;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Signaling events mediated by focal adhesion kinase;Reelin signaling pathway;PDGFR-beta signaling pathway;PDGFR-alpha signaling pathway;E-cadherin signaling in the nascent adherens junction;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.199

Intolerance Scores

• rvis_EVS: -1.77
• rvis_percentile_EVS: 2.32

Haploinsufficiency Scores

• pHI: 0.171
• hipred: Y
• hipred_score: 0.775
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.907

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rapgef1
• Phenotype: embryo phenotype; 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); 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); 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); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: activation of MAPKK activity;blood vessel development;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of neuron projection development;cytokine-mediated signaling pathway;Rap protein signal transduction;nerve growth factor signaling pathway;positive regulation of GTPase activity;regulation of JNK cascade;positive regulation of Ras protein signal transduction;negative regulation of Ras protein signal transduction;platelet-derived growth factor receptor signaling pathway;negative regulation of protein kinase B signaling;establishment of endothelial barrier;negative regulation of ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;cellular response to cAMP;negative regulation of canonical Wnt signaling pathway;activation of GTPase activity;cell-cell adhesion;regulation of cell junction assembly;positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis;cellular response to nerve growth factor stimulus;negative regulation of neural precursor cell proliferation
• Cellular component: cytoplasm;early endosome;cytosol;phagocytic vesicle membrane;protein-containing complex;perinuclear region of cytoplasm
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;Rap guanyl-nucleotide exchange factor activity;SH3 domain binding