SH3BP5L

protein-coding

SH3 binding domain protein 5 like

Gene summary

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in intracellular signal transduction. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_030645.3

Inheritance

—

ClinVar variants

U:52

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr1:248,810,446-248,825,915

External References & Databases

Ensembl (ENSG00000175137)

Transcript & Mutation Effects

hg38 • Region Span ~15.5 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 SH3BP5L variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 47

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030645.3. 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			50 clinvar			50
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	52	0	0	52

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030645.3	RefSeq	NP_085148.1	6	MANE Select
ENST00000366472.6	Ensembl	ENSP00000355428.5	6	MANE Select
NM_001322462.1	RefSeq	NP_001309391.1	4	Standard
NM_001322463.1	RefSeq	NP_001309392.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intracellular signal transduction
negative regulation of protein tyrosine kinase activity

Molecular Function

protein kinase inhibitor activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366472
Coding exons: 6
Length: 16185
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.68	189	266	0.710	0.0000187	2491
Missense (PolyPhen)		53	97.536	0.54339		938
Synonymous	0.657	103	112	0.921	0.00000774	833
Loss of Function	2.89	6	19.9	0.302	0.00000122	190

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00022	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.00010	0.000098	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.240
RVIS EVS: -0.74
RVIS percentile EVS: 13.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.847

Gene Damage Prediction

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