SIPA1L1: Signal-Induced Proliferation-Associated 1 Like 1
A Rap GTPase-Activating Protein Involved in Cell Signaling and Neurodevelopment
Gene Information Card
| Symbol | SIPA1L1 |
|---|---|
| Full Name | Signal-Induced Proliferation-Associated 1 Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.1 |
| NCBI Gene ID | 26037 ncbi.nlm.nih.gov/gene/26037 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q9H0H5 |
| OMIM ID | 602577 |
| HGNC ID | 20285 |
| Aliases | SPAR1, E6TP1, SIPA1L, KIAA0440 |
Description
SIPA1L1 (Signal-Induced Proliferation-Associated 1 Like 1) encodes a Rap GTPase-activating protein (RapGAP) that negatively regulates Rap1 and Rap2 signaling. The protein contains a PDZ domain, a C-terminal RapGAP domain, and a coiled-coil region. It is involved in synaptic plasticity, cell adhesion, and proliferation. SIPA1L1 is also known as E6TP1 due to its interaction with the E6 oncoprotein of human papillomavirus. Mutations and dysregulation of SIPA1L1 have been implicated in neurodevelopmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 69 | Loss-of-function mutations impair RapGAP activity, disrupting synaptic signaling and neuronal development | ClinVar, OMIM |
| Intellectual disability, autosomal dominant | De novo missense variants affecting protein stability or GAP function | ClinVar, OMIM |
| Cervical carcinoma | Interaction with HPV E6 protein leads to ubiquitin-mediated degradation, contributing to oncogenesis | UniProt, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Lung | 5.1 | Low |
| Kidney | 4.7 | Low |
| Liver | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression in neuronal lineage |
| HEK293 (embryonic kidney) | 6.8 | Moderate expression |
| HeLa (cervical carcinoma) | 4.1 | Low expression |
| A549 (lung carcinoma) | 3.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.187C>T (p.Arg63Trp) | Missense | Rare | Loss of RapGAP activity; associated with epileptic encephalopathy |
| c.1234G>A (p.Glu412Lys) | Missense | Rare | De novo variant; linked to intellectual disability |
| c.2560_2561del (p.Leu854fs) | Frameshift | Rare | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that reduce or abolish RapGAP activity, leading to dysregulated Rap signaling and neuronal hyperexcitability.
Gain of Function (GOF)
Not reported in SIPA1L1.
Dominant Negative (DN)
Not reported in SIPA1L1.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Rap GTPase binding |
| • PDZ domain binding | • Synaptic signaling |
| • Regulation of cell proliferation | • Negative regulation of Rap GTPase activity |
Pathways
• Rap1 signaling pathway
• Rap2 signaling pathway
• Synaptic vesicle cycle
• HPV E6-mediated degradation
Protein Summary
SIPA1L1 is a 1,804-amino acid protein that functions as a Rap GTPase-activating protein (RapGAP). It contains an N-terminal PDZ domain, a central coiled-coil region, and a C-terminal RapGAP domain. The protein localizes to synapses and regulates dendritic spine morphology and synaptic transmission. It also interacts with the HPV E6 oncoprotein, targeting it for proteasomal degradation. Alternative splicing generates multiple isoforms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIPA1L1 Knockout HEK293 Cell Line | EDJ-KQ1320 | Human | 26037 | Details Get a Quote |
| SIPA1L1 Knockout A-549 Cell Line | EDJ-KQ20755 | Human | 26037 | Details Get a Quote |
| SIPA1L1 Knockout HCT 116 Cell Line | EDJ-KQ20756 | Human | 26037 | Details Get a Quote |
| SIPA1L1 Knockout HeLa Cell Line | EDJ-KQ20757 | Human | 26037 | Details Get a Quote |
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