SH3BP1

SH3 domain binding protein 1, the group of AH/BAR family Rho GTPase activating proteins|N-BAR domain containing

Basic information

Region (hg38): 22:37634654-37656117

Links

ENSG00000100092 ∙ NCBI:23616 ∙ OMIM:617368 ∙ HGNC:10824 ∙ Uniprot:Q9Y3L3 ∙ 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 SH3BP1 gene.

• not_specified (109 variants)
• not_provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SH3BP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018957.6. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			108	1		109
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	108	2	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SH3BP1	protein_coding	protein_coding	ENST00000357436	18	32279

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0105	0.989	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.58	305	393	0.776	0.0000231	4425
Missense in Polyphen		107	157.99	0.67724		1818
Synonymous	-0.244	172	168	1.02	0.0000106	1465
Loss of Function	3.45	9	29.1	0.310	0.00000123	361

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000169	0.000152
Ashkenazi Jewish	0.000111	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000101	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000993	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase activating protein (GAP) which specifically converts GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form. By specifically inactivating RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration (PubMed:21658605). Also negatively regulates CDC42 in the process of actin remodeling and the formation of epithelial cell junctions (PubMed:22891260). Through its GAP activity toward RAC1 and/or CDC42 plays a specific role in phagocytosis of large particles. Specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, inactivates RAC1 and/or CDC42 allowing the reorganization of the underlying actin cytoskeleton required for engulfment (PubMed:26465210). It also plays a role in angiogenesis and the process of repulsive guidance as part of a semaphorin- plexin signaling pathway. Following the binding of PLXND1 to extracellular SEMA3E it dissociates from PLXND1 and inactivates RAC1, inducing the intracellular reorganization of the actin cytoskeleton and the collapse of cells (PubMed:24841563). {ECO:0000269|PubMed:21658605, ECO:0000269|PubMed:22891260, ECO:0000269|PubMed:24841563, ECO:0000269|PubMed:26465210}.

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.420
• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.74

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.542
• ghis: 0.524

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.758

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sh3bp1

Gene ontology

• Biological process: phagocytosis, engulfment;actin filament organization;cell migration;regulation of actin filament depolymerization;regulation of actin cytoskeleton organization;cell junction assembly;regulation of blood vessel endothelial cell migration;positive regulation of GTPase activity;establishment of epithelial cell apical/basal polarity;filopodium assembly;negative regulation of small GTPase mediated signal transduction;semaphorin-plexin signaling pathway;ruffle assembly
• Cellular component: exocyst;phagocytic cup;nucleus;cytosol;adherens junction;bicellular tight junction;lamellipodium;cell leading edge
• Molecular function: GTPase activator activity;protein binding;SH3 domain binding;semaphorin receptor binding;Rac GTPase binding