RAP1B

RAP1B, member of RAS oncogene family, the group of RAS type GTPase family

Basic information

Region (hg38): 12:68610854-68671901

Links

ENSG00000127314 ∙ NCBI:5908 ∙ OMIM:179530 ∙ HGNC:9857 ∙ Uniprot:P61224 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic constitutional thrombocytopenia (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies	AD	Allergy/Immunology/Infectious; Cardiovascular	Some individuals have been described as being susceptible to infections, and awareness may allow early and aggressive management of infections; The condition can involve congenital cardiovascular anomalies, and awareness may allow early diagnosis and management;	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Endocrine; Hematologic; Musculoskeletal; Neurologic; Renal	32627184; 35451551; 37850357

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAP1B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAP1B 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				5	1	6
missense		1	2			3
nonsense			1		1	2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				2		2
non coding					12	12
Total	0	1	4	5	14

Variants in RAP1B

This is a list of pathogenic ClinVar variants found in the RAP1B region.

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

Position	Type	Phenotype	Significance	ClinVar
12-68648409-G-A			Benign (Jun 20, 2021)
12-68648715-A-G			Benign (Nov 12, 2018)
12-68648759-G-A		Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies	Pathogenic (Mar 06, 2024)
12-68648759-G-T		Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies	Pathogenic (Mar 06, 2024)
12-68648910-T-G			Benign (May 14, 2021)
12-68650387-A-AT		RAP1B-related disorder	Likely benign (Jun 06, 2019)
12-68650446-C-T			Uncertain significance (Mar 09, 2023)
12-68650501-G-T			Benign (May 22, 2021)
12-68650696-T-G			Benign (Jun 20, 2021)
12-68652044-C-G		See cases • Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies	Likely pathogenic (Sep 03, 2021)
12-68652046-G-A		Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies	Pathogenic (Mar 06, 2024)
12-68652046-G-C		Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies	Pathogenic (Mar 06, 2024)
12-68653883-G-A			Benign (May 14, 2021)
12-68654105-A-T			Likely benign (Jul 30, 2018)
12-68654111-G-A			Uncertain significance (Aug 08, 2017)
12-68654177-C-T			Benign (Dec 31, 2019)
12-68654201-C-T			Likely benign (Aug 07, 2018)
12-68654206-T-C			Uncertain significance (Jul 26, 2022)
12-68654351-T-TG			Benign (May 14, 2021)
12-68654358-G-A			Benign (May 22, 2021)
12-68654543-G-A			Benign (Jun 20, 2021)
12-68656332-G-A			Likely benign (Jun 08, 2018)
12-68656386-A-G		RAP1B-related disorder	Likely benign (Jul 30, 2019)
12-68656392-A-G			Likely benign (Dec 31, 2019)
12-68656419-T-C			Likely benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAP1B	protein_coding	protein_coding	ENST00000250559	6	49754

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.910	0.0899	125456	0	1	125457	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.60	24	95.5	0.251	0.00000503	1193
Missense in Polyphen		3	29.273	0.10249		436
Synonymous	-0.453	36	32.7	1.10	0.00000169	336
Loss of Function	2.96	1	12.1	0.0823	5.78e-7	150

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000882
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction. Plays a role in the establishment of basal endothelial barrier function. {ECO:0000269|PubMed:18660803, ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:21840392}.
• Pathway: Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Integrin-mediated Cell Adhesion;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Androgen Receptor Network in Prostate Cancer;Corticotropin-releasing hormone signaling pathway;Common Pathways Underlying Drug Addiction;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;MET in type 1 papillary renal cell carcinoma;Ras Signaling;MAP2K and MAPK activation;Neutrophil degranulation;Disease;Signal Transduction;GPCR Adenosine A2A receptor;GRB2:SOS provides linkage to MAPK signaling for Integrins ;p130Cas linkage to MAPK signaling for integrins;Integrin alphaIIb beta3 signaling;HGF;Innate Immune System;Immune System;Rap1 signalling;Adaptive Immune System;MET activates RAP1 and RAC1;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;Integrin signaling;CXCR4-mediated signaling events;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;IFN-gamma pathway;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Nectin adhesion pathway;Neurotrophic factor-mediated Trk receptor signaling;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Signaling events mediated by focal adhesion kinase;amb2 Integrin signaling;EPHB forward signaling;PDGFR-beta signaling pathway;Trk receptor signaling mediated by the MAPK pathway;E-cadherin signaling in the nascent adherens junction (Consensus)

Intolerance Scores

• loftool: 0.493
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.668
• hipred: Y
• hipred_score: 0.825
• ghis: 0.614

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Rap1b
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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); reproductive system 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)

Zebrafish Information Network

• Gene name: rap1b
• Affected structure: endothelial cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: cell population proliferation;response to carbohydrate;microvillus assembly;Rap protein signal transduction;cellular response to drug;interleukin-12-mediated signaling pathway;neutrophil degranulation;establishment of endothelial barrier;positive regulation of ERK1 and ERK2 cascade;cellular response to cAMP;cellular response to gonadotropin-releasing hormone;regulation of cell junction assembly;regulation of establishment of cell polarity;negative regulation of synaptic vesicle exocytosis
• Cellular component: lipid droplet;cytosol;plasma membrane;cell-cell junction;membrane;azurophil granule membrane;membrane raft;extracellular exosome
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding;protein-containing complex binding