SH3BP5

protein-coding

SH3 domain binding protein 5

Gene summary

Enables guanyl-nucleotide exchange factor activity and protein kinase inhibitor activity. Acts upstream of or within intracellular signal transduction. Located in cytoplasmic vesicle membrane and nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_004844.5

Inheritance

—

ClinVar variants

U:71B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr3:15,254,353-15,341,368

External References & Databases

Ensembl (ENSG00000131370)

Transcript & Mutation Effects

hg38 • Region Span ~87.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SH3BP5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004844.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			61 clinvar			61
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			7 clinvar	1 clinvar		8
Total	0	0	71	2	0	73

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004844.5	RefSeq	NP_004835.2	9	MANE Select
ENST00000383791.8	Ensembl	ENSP00000373301.3	9	MANE Select
NM_001018009.4	RefSeq	NP_001018009.2	6	Standard
ENST00000366391.6	Ensembl	ENSP00000394115.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

BCR signaling pathway

Biological Process

signal transduction
intracellular signal transduction
negative regulation of protein tyrosine kinase activity

Molecular Function

protein kinase inhibitor activity
protein binding
SH3 domain binding

Cellular Component

nucleoplasm
cytoplasm
mitochondrion
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000383791
Coding exons: 9
Length: 86516
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.962	226	271	0.835	0.0000157	2976
Missense (PolyPhen)		45	76.51	0.58816		828
Synonymous	-1.40	127	108	1.17	0.00000653	875
Loss of Function	2.91	6	20.0	0.299	0.00000103	239

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits the auto- and transphosphorylation activity of BTK. Plays a negative regulatory role in BTK-related cytoplasmic signaling in B-cells. May be involved in BCR-induced apoptotic cell death. {ECO:0000269|PubMed:10339589, ECO:0000269|PubMed:9571151}.;

Recessive Scores

pRec: 0.271

Intolerance Scores

LoFtool: 0.120
RVIS EVS: 0.31
RVIS percentile EVS: 72.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.796

Gene Damage Prediction

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