RAPGEF4

Rap guanine nucleotide exchange factor 4

Basic information

Region (hg38): 2:172735274-173052893

Links

ENSG00000091428 ∙ NCBI:11069 ∙ OMIM:606058 ∙ HGNC:16626 ∙ Uniprot:Q8WZA2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• prostate cancer (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAPGEF4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAPGEF4 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	4	6
missense			43	3	2	48
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	43	5	6

Variants in RAPGEF4

This is a list of pathogenic ClinVar variants found in the RAPGEF4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-172736006-A-G		not specified	Uncertain significance (Sep 16, 2021)
2-172795080-G-A		not specified	Uncertain significance (Nov 21, 2022)
2-172795130-A-G			Likely benign (Jun 06, 2018)
2-172797542-A-G		not specified	Uncertain significance (May 05, 2023)
2-172814348-C-T		not specified	Uncertain significance (Jan 31, 2024)
2-172814354-G-A		not specified	Uncertain significance (Aug 12, 2021)
2-172814390-C-T		not specified	Uncertain significance (May 20, 2024)
2-172814393-A-G		not specified	Uncertain significance (Jul 15, 2021)
2-172917824-G-A		not specified	Uncertain significance (Mar 18, 2024)
2-172961128-T-A		not specified	Uncertain significance (Jun 05, 2023)
2-172961162-G-A		not specified	Uncertain significance (Jun 10, 2024)
2-172961223-A-G			Benign (Apr 25, 2018)
2-172967270-A-C		not specified	Uncertain significance (Dec 19, 2023)
2-172967317-G-A		not specified	Uncertain significance (Dec 20, 2023)
2-172967323-G-A		not specified	Uncertain significance (Feb 05, 2024)
2-172967362-T-C			Benign (Apr 25, 2018)
2-172983551-A-G		not specified	Uncertain significance (Sep 27, 2021)
2-172985490-G-A		not specified	Uncertain significance (Dec 19, 2023)
2-172988220-C-T		not specified	Uncertain significance (Nov 08, 2022)
2-172988774-G-A		not specified	Uncertain significance (Aug 02, 2023)
2-172990813-G-C		not specified	Uncertain significance (Jun 18, 2021)
2-172990883-G-A		not specified	Uncertain significance (Mar 29, 2024)
2-172996518-A-G		not specified	Uncertain significance (Aug 30, 2021)
2-172996521-A-G			Benign (Jun 06, 2018)
2-172996524-C-T		not specified	Uncertain significance (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAPGEF4	protein_coding	protein_coding	ENST00000397081	31	317620

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00782	124762	0	34	124796	0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	447	570	0.784	0.0000318	6629
Missense in Polyphen		165	231.91	0.71149		2686
Synonymous	0.358	200	207	0.968	0.0000118	1894
Loss of Function	6.25	12	67.4	0.178	0.00000397	746

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000187	0.000187
Ashkenazi Jewish	0.00	0.00
East Asian	0.000279	0.000278
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.000279	0.000278
South Asian	0.000229	0.000229
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA- independent exocytosis through interaction with RIMS2 (By similarity). {ECO:0000250, ECO:0000269|PubMed:10777494, ECO:0000269|PubMed:9856955}.
• Pathway: Adrenergic signaling in cardiomyocytes - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Signal Transduction;Integrin alphaIIb beta3 signaling;Immune System;Metabolism;Rap1 signalling;Adaptive Immune System;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;GPCR signaling-G alpha s Epac and ERK;Platelet Aggregation (Plug Formation);Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;Integrin signaling;Hemostasis;Integration of energy metabolism (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.583
• rvis_EVS: -0.77
• rvis_percentile_EVS: 13.15

Haploinsufficiency Scores

• pHI: 0.145
• hipred: Y
• hipred_score: 0.680
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.844

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rapgef4
• 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); homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;small GTPase mediated signal transduction;calcium ion regulated exocytosis;regulation of exocytosis;cAMP-mediated signaling;insulin secretion;regulation of insulin secretion;regulation of synaptic vesicle cycle
• Cellular component: cytosol;plasma membrane;membrane;hippocampal mossy fiber to CA3 synapse
• Molecular function: guanyl-nucleotide exchange factor activity;Ras guanyl-nucleotide exchange factor activity;protein binding;Ras GTPase binding;cAMP binding