RAPGEF5

Rap guanine nucleotide exchange factor 5

Basic information

Region (hg38): 7:22118235-22357154

Links

ENSG00000136237 ∙ NCBI:9771 ∙ OMIM:609527 ∙ HGNC:16862 ∙ Uniprot:Q92565 ∙ 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 RAPGEF5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAPGEF5 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						0
missense			35	2		37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	35	2	0

Variants in RAPGEF5

This is a list of pathogenic ClinVar variants found in the RAPGEF5 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-22122482-T-C		not specified	Uncertain significance (Sep 14, 2022)
7-22125636-C-T		not specified	Uncertain significance (Jul 12, 2023)
7-22131087-G-A		Dilated cardiomyopathy 1A	Likely pathogenic (-)
7-22136938-A-T		not specified	Uncertain significance (Nov 09, 2021)
7-22136966-A-C		not specified	Uncertain significance (Jan 03, 2024)
7-22140044-C-T			Uncertain significance (Oct 02, 2023)
7-22145048-C-T		not specified	Uncertain significance (Jun 29, 2023)
7-22146910-T-C		not specified	Uncertain significance (Oct 12, 2021)
7-22146985-C-T		not specified	Uncertain significance (Mar 25, 2024)
7-22150442-T-C		not specified	Uncertain significance (Dec 16, 2023)
7-22150498-T-C		not specified	Uncertain significance (Feb 28, 2024)
7-22154502-T-C		not specified	Uncertain significance (Jul 29, 2023)
7-22154593-C-T		not specified	Uncertain significance (May 04, 2023)
7-22156815-T-G		not specified	Uncertain significance (Mar 01, 2024)
7-22156857-T-C		not specified	Uncertain significance (Sep 13, 2023)
7-22160522-G-A		not specified	Uncertain significance (May 04, 2023)
7-22160529-C-A		not specified	Uncertain significance (Oct 25, 2022)
7-22162419-T-C		not specified	Uncertain significance (Jul 25, 2023)
7-22162491-C-T		not specified	Uncertain significance (Dec 28, 2022)
7-22162492-G-A		not specified	Likely benign (Oct 26, 2022)
7-22162506-T-A		not specified	Uncertain significance (May 23, 2023)
7-22193412-G-A		not specified	Uncertain significance (Oct 22, 2021)
7-22193921-T-C		not specified	Uncertain significance (Jun 07, 2023)
7-22193930-G-A		not specified	Uncertain significance (Jun 11, 2021)
7-22193992-G-C		not specified	Likely benign (Dec 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAPGEF5	protein_coding	protein_coding	ENST00000344041	23	238908

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0190	124626	0	10	124636	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	276	364	0.759	0.0000186	4799
Missense in Polyphen		94	144.4	0.65096		2003
Synonymous	0.224	131	134	0.975	0.00000734	1266
Loss of Function	5.30	8	47.4	0.169	0.00000251	574

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000203	0.000203
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000684	0.0000556
Finnish	0.0000466	0.0000464
European (Non-Finnish)	0.0000178	0.0000177
Middle Eastern	0.0000684	0.0000556
South Asian	0.00	0.00
Other	0.000169	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation. {ECO:0000269|PubMed:10777494, ECO:0000269|PubMed:10934204}.
• Pathway: Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Pathways in clear cell renal cell carcinoma;Ras Signaling (Consensus)

Recessive Scores

• pRec: 0.0809

Intolerance Scores

• loftool: 0.526
• rvis_EVS: -0.98
• rvis_percentile_EVS: 8.8

Haploinsufficiency Scores

• pHI: 0.112
• hipred: Y
• hipred_score: 0.819
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.788

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rapgef5

Gene ontology

• Biological process: small GTPase mediated signal transduction;nervous system development
• Cellular component: nucleus;nucleoplasm;nuclear body
• Molecular function: Ras guanyl-nucleotide exchange factor activity;Rap guanyl-nucleotide exchange factor activity;GTP-dependent protein binding