ABI1 (ABL Interactor 1) Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the ABI1 gene, its protein product, associated diseases, expression patterns, and mutations, based on authoritative genomic databases.
Gene Information Card
| Symbol | ABI1 |
|---|---|
| Full Name | abl-interactor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 10p12.2 |
| NCBI Gene ID | 10006 ncbi.nlm.nih.gov/gene/10006 |
| Ensembl ID | ENSG00000138448 |
| UniProt ID | Q9NYB0 |
| OMIM ID | 603050 |
| HGNC ID | 8473 |
| Aliases | ABI-1, E3B1, SSH3BP1, NAP1BP |
Description
The ABI1 gene encodes the Abl interactor 1 protein, a key component of the WAVE (WASP-family verprolin homologous) regulatory complex (WRC). This complex is essential for actin cytoskeleton remodeling, playing a critical role in cell motility, morphogenesis, and vesicle trafficking. ABI1 acts as a scaffold protein, linking the WAVE complex to activated ABL tyrosine kinases and other signaling molecules. Through its interaction with the actin cytoskeleton, ABI1 is involved in fundamental cellular processes including proliferation, differentiation, and adhesion. Dysregulation of ABI1 expression and function has been implicated in various cancers, where it can influence tumor invasion and metastasis, as well as in neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | Altered ABI1 expression affects actin dynamics and cell motility, potentially promoting tumor invasion and metastasis. It can also influence androgen receptor signaling. | Evidence from expression studies and functional assays in cell lines and animal models, as cited in NCBI Gene and PubMed literature. |
| Breast Cancer | ABI1 is involved in regulating the EGFR and integrin signaling pathways, which are crucial for cancer cell migration and invasion. Reduced expression is associated with increased metastatic potential. | Studies in breast cancer cell lines and clinical samples, referenced in NCBI Gene and UniProt. |
| Colorectal Cancer | ABI1 expression is frequently downregulated, which may contribute to tumor progression by disrupting the WAVE complex and enhancing cell migration. | Expression analysis in tumor tissues and cell lines, as documented in NCBI Gene and COSMIC. |
| Gastric Cancer | ABI1 can act as a tumor suppressor, and its loss is associated with increased cell proliferation and invasion, potentially through the regulation of the PI3K/Akt signaling pathway. | Functional studies in gastric cancer cell lines, as reported in NCBI Gene and PubMed. |
| Intellectual Disability | Homozygous mutations in the ABI1 gene have been identified as a cause of a syndromic form of intellectual disability, affecting neuronal development and function. | Case reports and genetic studies, as documented in OMIM (603050). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 31.2 | High |
| Lymph Node | 25.4 | High |
| Testis | 22.8 | High |
| Spleen | 18.5 | Medium |
| Lung | 15.1 | Medium |
| Liver | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (Leukemia) | 28.5 | High expression; used in studies of ABL signaling. |
| MCF7 (Breast Cancer) | 22.1 | Moderate expression; relevant for breast cancer research. |
| A549 (Lung Cancer) | 18.7 | Moderate expression; used in lung cancer studies. |
| HepG2 (Liver Cancer) | 12.3 | Low expression; reflects lower liver expression. |
| SH-SY5Y (Neuroblastoma) | 35.2 | High expression; useful for neuronal function studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.835C>T (p.Arg279Ter) | Nonsense | Rare | Introduces a premature stop codon, leading to a truncated, likely non-functional protein. Associated with intellectual disability. |
| c.1129A>G (p.Thr377Ala) | Missense | Rare | Amino acid substitution in a conserved region; functional impact is uncertain but may affect protein stability or interactions. |
| c.1450G>A (p.Val484Met) | Missense | Rare | Substitution in the SH3 domain, potentially altering binding to proline-rich motifs of partner proteins. |
| c.1660C>T (p.Arg554Cys) | Missense | Rare | Located in the proline-rich region; may affect interactions with ABL kinase. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations, such as the nonsense mutation p.Arg279Ter, are associated with autosomal recessive intellectual disability. These mutations disrupt the protein's ability to regulate actin dynamics, leading to impaired neuronal development and function.
Gain of Function (GOF)
No clear gain-of-function mutations have been described for ABI1 in the context of cancer. Instead, altered expression levels (both up and down) are more commonly observed, which can disrupt the stoichiometry of the WAVE complex and promote oncogenic signaling.
Dominant Negative (DN)
While not definitively proven, certain missense mutations in the SH3 domain or proline-rich regions could potentially act in a dominant-negative manner. Such mutations might bind to partner proteins but fail to recruit downstream effectors, thereby inhibiting the function of the wild-type protein.
View complete mutation data：
Gene Ontology (GO)
| • actin binding | • protein binding |
| • SH3 domain binding | • signal transducer activity |
| • actin cytoskeleton organization | • cell migration |
| • cell morphogenesis | • regulation of cell growth |
| • signal transduction | • vesicle-mediated transport |
Pathways
• Regulation of actin dynamics for phagocytic cup formation
• Rho GTPase cycle
• Signaling by Rho GTPases
• RHO GTPases Activate WASPs and WAVEs
• Axon guidance
Protein Summary
The ABI1 protein is a 55 kDa adaptor protein that serves as a critical regulator of the actin cytoskeleton. It is a core component of the WAVE regulatory complex (WRC), where it stabilizes the complex and links it to upstream signals from Rac GTPase. Through this role, ABI1 is essential for the formation of lamellipodia, which are sheet-like protrusions that drive cell migration. ABI1 also interacts directly with the Abl tyrosine kinase, modulating its activity and localizing it to sites of actin remodeling. Beyond its role in cell motility, ABI1 is involved in receptor endocytosis, vesicle trafficking, and transcriptional regulation. Its function is tightly regulated by tyrosine phosphorylation and ubiquitin-mediated degradation. In cancer, ABI1 can act as either a tumor suppressor or promoter depending on the cellular context, highlighting its complex role in oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABI1 Knockout HEK293 Cell Line | EDJ-KQ6225 | Human | 10006 | Details Get a Quote |
| ABI1 Knockout A-549 Cell Line | EDJ-KQ31437 | Human | 10006 | Details Get a Quote |
| ABI1 Knockout HCT 116 Cell Line | EDJ-KQ31439 | Human | 10006 | Details Get a Quote |
| ABI1 Knockout HeLa Cell Line | EDJ-KQ31440 | Human | 10006 | Details Get a Quote |
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