SH3GL2
protein-codingSH3 domain containing GRB2 like 2, endophilin A1, the group of N-BAR domain containing
Gene summary
Enables identical protein binding activity. Involved in negative regulation of blood-brain barrier permeability; negative regulation of gene expression; and negative regulation of signal transduction. Located in perinuclear region of cytoplasm. Implicated in Parkinson's disease. [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 ~218.1 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 SH3GL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003026.5. 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 | 1 | ||||
| missense | 38 | 38 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 38 | 0 | 1 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003017.1 | 9 | MANE Select | |
| Ensembl | ENSP00000369981.4 | 9 | MANE Select | |
| Ensembl | ENSP00000555110.1 | 8 | Standard | |
| Ensembl | ENSP00000555110.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- EGF-EGFR Signaling Pathway
- Developmental Biology
- Golgi Associated Vesicle Biogenesis
- Lysosome Vesicle Biogenesis
Biological Process
- regulation of receptor internalization
- signal transduction
- central nervous system development
- synaptic vesicle uncoating
- antigen processing and presentation of exogenous peptide antigen via MHC class II
Molecular Function
- protein binding
- protein C-terminus binding
- lipid binding
- protein kinase binding
- identical protein binding
Cellular Component
- Golgi membrane
- early endosome
- cytosol
- plasma membrane
- clathrin-coated endocytic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380607
- Coding exons
- 9
- Length
- 218048
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125718
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.963 | 153 | 190 | 0.804 | 0.00000961 | 2323 |
| Missense (PolyPhen) | 46 | 74.133 | 0.62051 | 925 | ||
| Synonymous | -2.04 | 89 | 67.6 | 1.32 | 0.00000353 | 642 |
| Loss of Function | 2.30 | 10 | 21.5 | 0.465 | 0.00000126 | 235 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes. {ECO:0000250|UniProtKB:Q62420}.;
Recessive Scores
- pRec
- 0.208
Intolerance Scores
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |