SYNJ2
protein-codingsynaptojanin 2, the group of Phosphoinositide phosphatases
Gene summary
The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~117.3 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 SYNJ2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003898.4. 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 | 6 | 6 | 12 | |||
| missense | 240 | 11 | 1 | 252 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 253 | 17 | 1 | 271 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003889.1 | 27 | MANE Select | |
| Ensembl | ENSP00000347792.4 | 27 | MANE Select | |
| RefSeq | NP_001171559.1 | 23 | Standard | |
| RefSeq | NP_001397876.1 | 27 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inositol phosphate metabolism - Homo sapiens (human)
- Phosphatidylinositol signaling system - Homo sapiens (human)
- D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis
- superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism
- Vesicle-mediated transport
Biological Process
- phosphatidylinositol biosynthetic process
- brain development
- phosphatidylinositol-3-phosphate biosynthetic process
- inositol phosphate dephosphorylation
- phosphatidylinositol dephosphorylation
Molecular Function
- RNA binding
- phosphatidylinositol-3-phosphatase activity
- phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity
- protein binding
- SH3 domain binding
Cellular Component
- cytosol
- membrane raft
- perinuclear region of cytoplasm
- presynapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355585
- Coding exons
- 27
- Length
- 117321
- Individuals with no LoFs
- 125527
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 221
- Defined
- 125748
- p
- 0.000879
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.715 | 824 | 884 | 0.932 | 0.0000540 | 9723 |
| Missense (PolyPhen) | 248 | 280.42 | 0.8844 | 2933 | ||
| Synonymous | -0.110 | 377 | 374 | 1.01 | 0.0000265 | 3030 |
| Loss of Function | 3.55 | 32 | 62.2 | 0.515 | 0.00000299 | 729 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00086 | 0.00085 | rare |
| South Asian | 0.0021 | 0.0021 | notable |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inositol 5-phosphatase which may be involved in distinct membrane trafficking and signal transduction pathways. May mediate the inhibitory effect of Rac1 on endocytosis.;
Intolerance Scores
- LoFtool
- 0.108
- RVIS EVS
- -1.9
- RVIS percentile EVS
- 1.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |