SIPA1L3 Gene: Signal-Induced Proliferation-Associated 1 Like 3
Comprehensive genomic and functional annotation of SIPA1L3, a Rap GTPase-activating protein implicated in neurodevelopmental and ocular disorders.
Gene Information Card
| Symbol | SIPA1L3 |
|---|---|
| Full Name | Signal-induced proliferation-associated 1 like 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 23094 ncbi.nlm.nih.gov/gene/23094 |
| Ensembl ID | ENSG00000105767 |
| UniProt ID | O60292 |
| OMIM ID | 616655 |
| HGNC ID | 24898 |
| Aliases | SPAL3, KIAA0545, E6TP1 beta |
Description
SIPA1L3 encodes a member of the signal-induced proliferation-associated (SIPA) family of Rap GTPase-activating proteins (RapGAPs). The protein contains a RapGAP domain and a PDZ domain, and functions as a negative regulator of Rap-mediated signaling. SIPA1L3 is involved in cell adhesion, migration, and cytoskeletal dynamics. Mutations in this gene have been associated with neurodevelopmental disorders and ocular anomalies, including coloboma and microphthalmia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with or without ocular anomalies | Loss-of-function mutations in SIPA1L3 disrupt Rap signaling, affecting neuronal migration and eye development. | PMID: 28413018, ClinVar |
| Ocular coloboma | Missense and truncating variants impair RapGAP activity, leading to defective optic fissure closure. | PMID: 28413018, OMIM #616655 |
| Microphthalmia | Homozygous loss-of-function variants reduce SIPA1L3 expression, altering retinal progenitor cell proliferation. | PMID: 28413018 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Eye | 8.3 | Medium |
| Testis | 6.1 | Low |
| Lung | 4.7 | Low |
| Kidney | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 8.9 | Moderate expression |
| ARPE-19 (retinal pigment epithelium) | 7.4 | Moderate expression |
| HeLa (cervical carcinoma) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76*) | Nonsense | <0.01% | Loss of function; truncation of RapGAP domain |
| c.1015G>A (p.Gly339Arg) | Missense | <0.01% | Impaired RapGAP activity; associated with ocular coloboma |
| c.1687_1688del (p.Leu563Valfs*12) | Frameshift | <0.01% | Loss of function; predicted nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants (e.g., p.Arg76*, p.Leu563Valfs*12) lead to truncated or degraded protein, reducing RapGAP activity.
Gain of Function (GOF)
No gain-of-function mutations reported in SIPA1L3.
Dominant Negative (DN)
No dominant-negative mutations reported in SIPA1L3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rap1 signaling pathway (Reactome: R-HSA-392517)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
• Axon guidance (Reactome: R-HSA-422475)
Protein Summary
SIPA1L3 is a 1,331-amino-acid protein containing an N-terminal RapGAP domain and a C-terminal PDZ domain. It localizes to the cytoplasm and cell junctions, where it inactivates Rap1 and Rap2 by stimulating GTP hydrolysis. Through this activity, SIPA1L3 modulates cell adhesion, cytoskeletal organization, and neuronal migration. The protein is highly expressed in brain and eye tissues, consistent with its role in neurodevelopment and ocular morphogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIPA1L3 Knockout HEK293 Cell Line | EDJ-KQ1324 | Human | 23094 | Details Get a Quote |
| SIPA1L3 Knockout HCT 116 Cell Line | EDJ-KQ19419 | Human | 23094 | Details Get a Quote |
| SIPA1L3 Knockout A-549 Cell Line | EDJ-KQ20763 | Human | 23094 | Details Get a Quote |
| SIPA1L3 Knockout HeLa Cell Line | EDJ-KQ20764 | Human | 23094 | Details Get a Quote |
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