SH3GL3
protein-codingSH3 domain containing GRB2 like 3, endophilin A3, the group of N-BAR domain containing
Gene summary
Enables identical protein binding activity. Predicted to be involved in endocytosis and membrane organization. Predicted to be located in acrosomal vesicle and early endosome membrane. Predicted to be part of early endosome. Predicted to be active in several cellular components, including cytosol; glutamatergic synapse; and presynapse. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~171.5 kbGenCC 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 SH3GL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003027.5. 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 | 0 | |||||
| missense | 37 | 37 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 0 | 0 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003018.3 | 9 | MANE Select | |
| Ensembl | ENSP00000391372.2 | 9 | MANE Select | |
| RefSeq | NP_001288037.1 | 6 | Standard | |
| RefSeq | NP_001288038.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sh3gl3b | Danio rerio | Structure: blood cell Quality: accumulation abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- EGF-EGFR Signaling Pathway
- Disease
- Signal Transduction
- Vesicle-mediated transport
Biological Process
- endocytosis
- signal transduction
- central nervous system development
- positive regulation of neuron differentiation
- negative regulation of clathrin-dependent endocytosis
Molecular Function
- protein binding
- protein C-terminus binding
- lipid binding
- identical protein binding
Cellular Component
- acrosomal vesicle
- early endosome membrane
- presynapse
- postsynaptic endosome
- glutamatergic synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000427482
- Coding exons
- 9
- Length
- 171516
- Individuals with no LoFs
- 125707
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125748
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.21 | 138 | 184 | 0.750 | 0.00000975 | 2270 |
| Missense (PolyPhen) | 64 | 89.281 | 0.71684 | 1083 | ||
| Synonymous | -0.762 | 79 | 70.8 | 1.12 | 0.00000431 | 630 |
| Loss of Function | 2.24 | 10 | 21.1 | 0.474 | 0.00000125 | 248 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.660
- RVIS EVS
- 0.28
- RVIS percentile EVS
- 71.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |