RAPGEF3

Rap guanine nucleotide exchange factor 3

Basic information

Region (hg38): 12:47734362-47771040

Links

ENSG00000079337 ∙ NCBI:10411 ∙ OMIM:606057 ∙ HGNC:16629 ∙ Uniprot:O95398 ∙ 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 RAPGEF3 gene.

• Inborn genetic diseases (41 variants)
• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAPGEF3 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				3	2	5
missense			39	4	3	46
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	39	7	5

Variants in RAPGEF3

This is a list of pathogenic ClinVar variants found in the RAPGEF3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-47737573-C-G		not specified	Uncertain significance (Jun 27, 2022)
12-47737684-G-A			Benign (Aug 13, 2018)
12-47738226-G-A		not specified	Uncertain significance (Dec 03, 2021)
12-47738244-T-A		not specified	Uncertain significance (Jun 29, 2022)
12-47738707-T-A		not specified	Uncertain significance (May 08, 2023)
12-47740158-C-T		not specified	Uncertain significance (Feb 16, 2023)
12-47740161-A-G		not specified	Uncertain significance (Oct 10, 2023)
12-47740325-G-A		not specified	Uncertain significance (Jan 26, 2022)
12-47740712-C-T		not specified	Uncertain significance (Jun 27, 2023)
12-47740778-C-T		not specified	Uncertain significance (Sep 12, 2023)
12-47740784-G-A		not specified	Uncertain significance (May 04, 2023)
12-47740985-A-T			Benign (Jul 15, 2018)
12-47741039-A-G		not specified	Likely benign (Jun 21, 2022)
12-47741043-G-A			Benign (Jun 26, 2018)
12-47741542-C-T		not specified	Uncertain significance (Nov 17, 2023)
12-47743562-C-G		not specified	Uncertain significance (Nov 17, 2022)
12-47743576-A-G			Likely benign (Mar 01, 2023)
12-47743611-C-T		not specified	Uncertain significance (Aug 30, 2021)
12-47743616-G-T		not specified	Uncertain significance (Feb 09, 2023)
12-47743658-C-T		not specified	Uncertain significance (Nov 08, 2022)
12-47743665-T-C		not specified	Uncertain significance (May 04, 2023)
12-47744064-C-T		not specified	Uncertain significance (Feb 15, 2023)
12-47746879-T-C		not specified	Uncertain significance (Feb 28, 2023)
12-47747550-C-T			Benign (Jul 15, 2018)
12-47747553-C-T		not specified	Uncertain significance (Jun 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAPGEF3	protein_coding	protein_coding	ENST00000449771	28	36369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.07e-23	0.270	125617	0	131	125748	0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.867	498	555	0.897	0.0000343	5904
Missense in Polyphen		146	177.24	0.82374		1850
Synonymous	0.495	217	226	0.958	0.0000135	1885
Loss of Function	1.85	43	58.3	0.738	0.00000350	566

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00114	0.00111
Ashkenazi Jewish	0.000207	0.000198
East Asian	0.000599	0.000598
Finnish	0.000146	0.000139
European (Non-Finnish)	0.000440	0.000431
Middle Eastern	0.000599	0.000598
South Asian	0.00118	0.00118
Other	0.000492	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) for RAP1A and RAP2A small GTPases that is activated by binding cAMP. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which it activates the PI3K gamma complex and which is involved in angiogenesis. Plays a role in the modulation of the cAMP-induced dynamic control of endothelial barrier function through a pathway that is independent on Rho- mediated signaling. Required for the actin rearrangement at cell- cell junctions, such as stress fibers and junctional actin. {ECO:0000269|PubMed:10777494, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:9853756}.
• Pathway: Long-term potentiation - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);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);Leukocyte transendothelial migration - Homo sapiens (human);Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Corticotropin-releasing hormone signaling pathway;Signal Transduction;phospholipase c-epsilon pathway;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: 0.211

Intolerance Scores

• loftool: 0.770
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.59

Haploinsufficiency Scores

• pHI: 0.108
• hipred: Y
• hipred_score: 0.536
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rapgef3
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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)

Gene ontology

• Biological process: angiogenesis;signal transduction;cell population proliferation;cAMP-mediated signaling;Rap protein signal transduction;positive regulation of peptidyl-serine phosphorylation;negative regulation of syncytium formation by plasma membrane fusion;positive regulation of GTPase activity;positive regulation of angiogenesis;positive regulation of protein export from nucleus;regulation of insulin secretion;positive regulation of stress fiber assembly;positive regulation of syncytium formation by plasma membrane fusion;establishment of endothelial barrier;cellular response to cAMP;positive regulation of protein acetylation;regulation of actin cytoskeleton reorganization;regulation of histone H3-K9 acetylation
• Cellular component: plasma membrane;microvillus;endomembrane system;membrane;lamellipodium;filopodium;cortical actin cytoskeleton;extracellular exosome
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;Rap guanyl-nucleotide exchange factor activity;protein domain specific binding;cAMP binding