SH3GLB1
protein-codingSH3 domain containing GRB2 like, endophilin B1, the group of N-BAR domain containing|Protein phosphatase 1 regulatory subunits
Gene summary
This gene encodes a SRC homology 3 domain-containing protein. The encoded protein interacts with the proapoptotic member of the Bcl-2 family, Bcl-2-associated X protein (Bax) and may be involved in regulating apoptotic signaling pathways. This protein may also be involved in maintaining mitochondrial morphology. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.6 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 SH3GLB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016009.5. 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 | 42 | 42 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 43 | 0 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057093.1 | 9 | MANE Select | |
| Ensembl | ENSP00000473267.1 | 9 | MANE Select | |
| RefSeq | NP_001193580.1 | 10 | Standard | |
| RefSeq | NP_001193581.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Autophagy - animal - Homo sapiens (human)
- Nanoparticle triggered autophagic cell death
- Senescence and Autophagy in Cancer
Biological Process
- autophagy
- apoptotic process
- positive regulation of autophagy
- regulation of macroautophagy
- regulation of protein stability
Molecular Function
- protein binding
- lipid binding
- identical protein binding
- protein homodimerization activity
- cadherin binding
Cellular Component
- Golgi membrane
- autophagosome membrane
- cytoplasm
- mitochondrial outer membrane
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000482504
- Coding exons
- 11
- Length
- 43609
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125742
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.63 | 130 | 194 | 0.671 | 0.00000914 | 2531 |
| Missense (PolyPhen) | 46 | 84.375 | 0.54518 | 1098 | ||
| Synonymous | 1.01 | 56 | 66.5 | 0.843 | 0.00000312 | 704 |
| Loss of Function | 3.90 | 1 | 19.7 | 0.0509 | 8.27e-7 | 278 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000060 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be required for normal outer mitochondrial membrane dynamics (PubMed:15452144). Required for coatomer-mediated retrograde transport in certain cells (By similarity). May recruit other proteins to membranes with high curvature. May promote membrane fusion (PubMed:11604418). Involved in activation of caspase-dependent apoptosis by promoting BAX/BAK1 activation (PubMed:16227588). Isoform 1 acts proapoptotic in fibroblasts (By similarity). Involved in caspase-independent apoptosis during nutrition starvation and involved in the regulation of autophagy. Activates lipid kinase activity of PIK3C3 during autophagy probably by associating with the PI3K complex II (PI3KC3-C2) (PubMed:17891140). Associated with PI3KC3-C2 during autophagy may regulate the trafficking of ATG9A from the Golgi complex to the peripheral cytoplasm for the formation of autophagosomes by inducing Golgi membrane tubulation and fragmentation (PubMed:21068542). Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123). Isoform 2 acts antiapoptotic in neuronal cells; involved in maintenance of mitochondrial morphology and promotes neuronal viability (By similarity). {ECO:0000250|UniProtKB:Q9JK48, ECO:0000269|PubMed:11604418, ECO:0000269|PubMed:15452144, ECO:0000269|PubMed:17891140, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:21068542}.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- LoFtool
- 0.208
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.862
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |