SIPA1L1
protein-codingsignal induced proliferation associated 1 like 1, the group of PDZ domain containing
Gene summary
Predicted to enable GTPase activator activity; actin filament binding activity; and protein kinase binding activity. Predicted to be involved in several processes, including activation of GTPase activity; postsynaptic actin cytoskeleton organization; and regulation of postsynapse organization. Located in actin cytoskeleton and plasma membrane. [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 ~420.8 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 SIPA1L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001386936.1. 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 | 9 | 3 | 15 | ||
| missense | 228 | 4 | 2 | 234 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 238 | 13 | 5 | 256 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001373865.1 | 20 | MANE Select | |
| Ensembl | ENSP00000370630.3 | 20 | MANE Select | |
| RefSeq | NP_001271174.1 | 20 | Standard | |
| RefSeq | NP_001271175.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Rap1 signaling pathway - Homo sapiens (human)
- Neuronal System
- Neurexins and neuroligins
- Protein-protein interactions at synapses
Biological Process
- biological_process
- actin cytoskeleton reorganization
- regulation of GTPase activity
- ephrin receptor signaling pathway
- regulation of synaptic plasticity
Molecular Function
- molecular_function
- GTPase activator activity
- ephrin receptor binding
Cellular Component
- cellular_component
- cytoplasm
- cytoskeleton
- postsynaptic density
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000555818
- Coding exons
- 21
- Length
- 420781
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.98 | 763 | 1.03e+3 | 0.739 | 0.0000596 | 11852 |
| Missense (PolyPhen) | 304 | 473.47 | 0.64206 | 5474 | ||
| Synonymous | -0.0568 | 402 | 401 | 1.00 | 0.0000241 | 3581 |
| Loss of Function | 7.49 | 7 | 78.7 | 0.0890 | 0.00000477 | 888 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F- actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- RVIS EVS
- -2.73
- RVIS percentile EVS
- 0.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.728
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |