SH3BP4

protein-coding

SH3 domain binding protein 4

Gene summary

This gene encodes a protein with 3 Asn-Pro-Phe (NPF) motifs, an SH3 domain, a PXXP motif, a bipartite nuclear targeting signal, and a tyrosine phosphorylation site. This protein is involved in cargo-specific control of clathrin-mediated endocytosis, specifically controlling the internalization of a specific protein receptor. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014521.3

Inheritance

—

ClinVar variants

U:144B:22

Top phenotype

See cases

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr2:234,952,017-235,055,714

External References & Databases

Ensembl (ENSG00000130147)

Transcript & Mutation Effects

hg38 • Region Span ~103.7 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 SH3BP4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 140

not providedTotal: 16

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014521.3. 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			3 clinvar	7 clinvar	6 clinvar	16
missense			139 clinvar	8 clinvar	1 clinvar	148
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	144	15	7	166

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014521.3	RefSeq	NP_055336.1	4	MANE Select
ENST00000392011.7	Ensembl	ENSP00000375867.2	4	MANE Select
NM_001371302.1	RefSeq	NP_001358231.1	4	Standard
NM_001371303.1	RefSeq	NP_001358232.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in squamous cell - TarBase

Biological Process

endocytosis
negative regulation of cell population proliferation
positive regulation of autophagy
negative regulation of cell growth
negative regulation of TOR signaling

Molecular Function

GDP-dissociation inhibitor activity
protein binding
Ras GTPase binding
identical protein binding

Cellular Component

nucleus
cytoplasm
clathrin-coated pit
clathrin-coated vesicle
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409212
Coding exons: 4
Length: 103742
Individuals with no LoFs: 125697
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125748
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.628	539	582	0.927	0.0000380	6318
Missense (PolyPhen)		150	198.38	0.75611		2083
Synonymous	-0.644	281	268	1.05	0.0000201	1971
Loss of Function	3.35	10	29.7	0.337	0.00000153	325

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.0017	0.0017	notable
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin- mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy. {ECO:0000269|PubMed:16325581, ECO:0000269|PubMed:22575674}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.472
RVIS EVS: -0.72
RVIS percentile EVS: 14.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.742

Gene Damage Prediction

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