SH3BP2

SH3 domain binding protein 2, the group of Pleckstrin homology domain containing|SH2 domain containing

Basic information

Region (hg38): 4:2793070-2841098

Links

ENSG00000087266 ∙ NCBI:6452 ∙ OMIM:602104 ∙ HGNC:10825 ∙ Uniprot:P78314 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cherubism (Limited), mode of inheritance: AD
• cherubism (Strong), mode of inheritance: AD
• cherubism (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cherubism	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	11381256; 17368082; 18596838; 19017279; 20301316; 21045962; 22153076; 22640988; 22640403; 22795151
As bone lesions are typically self-limiting, surgical interventions treatment may not be necessary (with the exception of aggressive lesions resulting in severe functional issues, or for aesthetic reasons)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SH3BP2 gene.

• Fibrous dysplasia of jaw (622 variants)
• not provided (58 variants)
• Inborn genetic diseases (36 variants)
• not specified (11 variants)
• SH3BP2-related condition (5 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SH3BP2 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			7	112	12	131
missense	5	2	208	14	4	233
nonsense			3			3
start loss			1			1
frameshift			12			12
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)			3			3
splice region			8	12	3	23
non coding			47	67	115	229
Total	5	2	283	194	131

Variants in SH3BP2

This is a list of pathogenic ClinVar variants found in the SH3BP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-2812421-A-G			Benign (May 14, 2021)
4-2812446-C-T		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
4-2812466-C-T		SH3BP2-related disorder	Likely benign (May 10, 2022)
4-2812476-A-G		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
4-2818233-T-G		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
4-2818236-G-C		Inborn genetic diseases	Uncertain significance (May 23, 2023)
4-2818254-T-G		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
4-2818270-C-T		SH3BP2-related disorder	Uncertain significance (Jan 02, 2024)
4-2818281-G-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
4-2818299-G-A		Inborn genetic diseases	Uncertain significance (Aug 10, 2021)
4-2818312-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
4-2818442-C-G			Benign (May 16, 2021)
4-2818534-G-A			Benign (May 16, 2021)
4-2818833-G-T		Fibrous dysplasia of jaw	Benign (Jan 12, 2018)
4-2818834-A-C		Fibrous dysplasia of jaw	Benign (Jan 12, 2018)
4-2818976-C-T		Fibrous dysplasia of jaw	Benign (Jan 13, 2018)
4-2819024-C-T		Fibrous dysplasia of jaw	Uncertain significance (Jun 14, 2016)
4-2820435-G-A			Benign (May 14, 2021)
4-2820562-C-A		not specified	Benign (Nov 12, 2023)
4-2820580-T-C		Fibrous dysplasia of jaw	Benign (Jul 15, 2021)
4-2820618-A-G		Fibrous dysplasia of jaw	Uncertain significance (Jul 26, 2023)
4-2820623-G-A		Fibrous dysplasia of jaw	Likely benign (Jan 09, 2023)
4-2820625-C-T		Fibrous dysplasia of jaw	Uncertain significance (Aug 21, 2022)
4-2820630-G-A		Inborn genetic diseases • Fibrous dysplasia of jaw	Uncertain significance (Jan 04, 2024)
4-2820632-G-C		Fibrous dysplasia of jaw	Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SH3BP2	protein_coding	protein_coding	ENST00000503393	13	48076

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.16e-11	0.303	125638	0	110	125748	0.000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.292	344	360	0.957	0.0000236	3972
Missense in Polyphen		97	105.97	0.91532		1087
Synonymous	-1.45	179	156	1.15	0.0000115	1287
Loss of Function	1.02	20	25.6	0.781	0.00000136	303

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000390	0.000386
Ashkenazi Jewish	0.000300	0.000298
East Asian	0.000218	0.000217
Finnish	0.00163	0.000739
European (Non-Finnish)	0.000660	0.000615
Middle Eastern	0.000218	0.000217
South Asian	0.000131	0.000131
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism.
• Disease: DISEASE: Cherubism (CRBM) [MIM:118400]: An autosomal dominant syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling. {ECO:0000269|PubMed:11381256, ECO:0000269|PubMed:12900899, ECO:0000269|PubMed:14577811}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Natural killer cell mediated cytotoxicity - Homo sapiens (human);B Cell Receptor Signaling Pathway;TCR;BCR;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.0376
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.45

Haploinsufficiency Scores

• pHI: 0.137
• hipred: Y
• hipred_score: 0.756
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.760

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sh3bp2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary 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); hematopoietic system phenotype; vision/eye 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); limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype

Gene ontology

• Biological process: signal transduction;positive regulation of signal transduction
• Molecular function: phosphotyrosine residue binding;SH3/SH2 adaptor activity;protein binding;SH3 domain binding