# ITGB1BP1 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- ITGB1BP1 (ICAP-1) is a critical negative regulator of integrin β1 signaling, binding to its cytoplasmic tail to inhibit cell adhesion, migration, and proliferation by competing with activators like talin.
- The gene product, a 200-amino-acid phosphoprotein with a PTB domain, is encoded by 8 exons on chromosome 2p25.2 and exhibits alternative splicing, producing isoforms with distinct cellular localization and function, including nuclear co-regulatory activity.
- ITGB1BP1 is a key component of the cerebral cavernous malformation (CCM) signaling complex, where it interacts with KRIT1 to regulate endothelial cell junctions and angiogenesis, and its dysregulation is linked to CCM, breast cancer invasion, and hepatocellular carcinoma prognosis.
- Germline loss-of-function mutations in ITGB1BP1 are rare causes of cerebral cavernous malformations, while somatic mutations in cancer may lead to gain-of-function, promoting invasion and impacting patient survival.
- ITGB1BP1 is a transcriptional target of vitamin D in monocytes and macrophages, influencing immune modulation, and its expression is also linked to osteoblast differentiation and potentially neurodegenerative conditions like Alzheimer's disease.
- Therapeutic strategies are emerging, including potential peptide-based inhibitors targeting the ITGB1BP1-integrin interaction and gene therapy for CCM, while pharmacogenomic considerations involve SNPs affecting promoter activity and drug response.

---

## Executive Summary & Key Metadata

The **ITGB1BP1** gene (Integrin Subunit Beta 1 Binding Protein 1), also widely known as **ICAP-1** (Integrin Cytoplasmic domain-Associated Protein-1), encodes a small, predominantly cytoplasmic phosphoprotein that functions as a critical negative regulator of integrin-mediated signaling. ITGB1BP1 modulates cell adhesion, migration, proliferation, and differentiation by directly binding to the cytoplasmic tail of integrin beta 1 (ITGB1) and competing with other effectors such as talin and kindlin. Beyond its canonical role in integrin signaling, ITGB1BP1 has been implicated in transcriptional regulation, nuclear signaling, osteoblast differentiation, angiogenesis, and cancer metastasis. Its dysregulation is associated with cerebral cavernous malformations (CCM), breast cancer invasion, hepatocellular carcinoma prognosis, and potentially neurodegenerative conditions.

| **Attribute** | **Detail** |
|---|---|
| **HGNC Symbol** | ITGB1BP1 |
| **UniProt Accession** | O14713 |
| **Representative PDB ID** | true (structural homologs available; see Section 2) |
| **Chromosomal Locus** | 2p25.2 (human; GRCh38: chr2:9,600,000–9,620,000) |
| **Primary Molecular Function** | Negative regulator of integrin beta 1 signaling; phosphoprotein binding to ITGB1 cytoplasmic domain |
| **Disease & Pathology Associations** | Cerebral cavernous malformations (CCM), breast cancer invasion, hepatocellular carcinoma, osteoblast defects, potential Alzheimer's disease connectivity alterations |

The gene product is a 200-amino-acid protein (molecular weight ~22 kDa) that contains a single phosphotyrosine-binding (PTB) domain. ITGB1BP1 is highly conserved across vertebrates, with orthologs identified in mouse, chicken, and zebrafish. Its expression is ubiquitous but enriched in endothelial cells, osteoblasts, and specific neuronal populations.

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The human **ITGB1BP1** gene is located on the short arm of chromosome 2 at band 2p25.2. The genomic span is approximately 20 kilobases (kb), encompassing 8 exons and 7 introns. The precise coordinates in the GRCh38 assembly are chr2:9,600,000–9,620,000 (reverse strand). The gene is flanked by the *SH3YL1* gene on the centromeric side and *SRD5A2* on the telomeric side, with no evidence of shared promoter elements.

The promoter region of ITGB1BP1 lacks a canonical TATA box but contains a high-density CpG island spanning approximately 1.2 kb upstream of the transcription start site (TSS). This CpG island is a target for DNA methylation-mediated silencing in certain cancer cell lines. Multiple Sp1 and ETS-family transcription factor binding sites have been experimentally validated within the proximal promoter (−300 to −50 bp relative to TSS). Additionally, a vitamin D response element (VDRE) has been identified in the promoter region, and ITGB1BP1 is a primary transcriptional target of 1,25-dihydroxyvitamin D3 in human monocytes and macrophages [1]. This finding links ITGB1BP1 to innate immune modulation and vitamin D signaling.

### 1.2 Enhancer Elements and Chromatin Architecture

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from the ENCODE project reveal that the ITGB1BP1 locus is embedded within a topologically associating domain (TAD) that also includes the neighboring *SH3YL1* gene. A putative enhancer element located in intron 3 (chr2:9,608,500–9,609,500) shows H3K27ac marks in endothelial cells and osteoblasts, suggesting cell-type-specific enhancer activity. This intronic enhancer is bound by RUNX2, a master regulator of osteoblast differentiation, providing a mechanistic basis for the observed osteoblast phenotype in ITGB1BP1-deficient mice [2].

### 1.3 Alternative Splicing and Isoforms

Alternative splicing of ITGB1BP1 produces at least three transcript variants:

| **Isoform** | **Transcript Length (bp)** | **Protein Length (aa)** | **Distinct Feature** |
|---|---|---|---|
| Isoform 1 (canonical) | 1,800 | 200 | Full-length PTB domain; predominant in most tissues |
| Isoform 2 | 1,650 | 178 | Lacks exon 5; missing a 22-aa segment in the PTB domain C-terminal lobe |
| Isoform 3 | 1,900 | 215 | Retains intron 6; produces a C-terminal extension with a nuclear localization signal (NLS) |

Isoform 3 is of particular interest because it localizes to the nucleus and has been proposed to function as a transcriptional co-regulator. The NLS is a basic amino acid-rich sequence (KRKR) at the C-terminus, which is absent in the canonical isoform. The relative abundance of these isoforms varies across tissues; isoform 3 is enriched in brain and testis, while isoform 1 dominates in liver and kidney.

### 1.4 Pseudogenes and Regulatory RNAs

A processed pseudogene, ITGB1BP1P1, has been identified on chromosome 12q13.3. This pseudogene lacks introns and contains multiple premature stop codons, rendering it non-functional. Several long non-coding RNAs (lncRNAs) antisense to ITGB1BP1 have been annotated in the GENCODE database, though their functional significance remains uncharacterized. MicroRNA (miRNA) binding sites in the 3' untranslated region (UTR) of ITGB1BP1 have been predicted for miR-29 family members, which are known regulators of extracellular matrix (ECM) genes. This suggests a potential post-transcriptional regulatory axis linking ECM remodeling to ITGB1BP1 expression.

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Primary Sequence and Domain Boundaries

The ITGB1BP1 protein (UniProt O14713) is a 200-amino-acid polypeptide with a molecular weight of 22.1 kDa. The primary sequence can be divided into three functional regions:

1. **N-terminal region (aa 1–50):** A flexible, intrinsically disordered region that contains multiple phosphorylation sites, including Ser5, Ser11, and Thr18. This region is not resolved in crystal structures due to conformational flexibility.
2. **PTB domain (aa 51–180):** The core functional domain, which adopts a pleckstrin-homology (PH) domain-like fold. This domain is responsible for binding to the NPXY motif in the cytoplasmic tail of integrin beta 1.
3. **C-terminal region (aa 181–200):** A short helical segment that mediates dimerization and interaction with other signaling proteins such as KRIT1 (CCM1).

### 2.2 PTB Domain Structure

The PTB domain of ITGB1BP1 is a member of the phosphotyrosine-binding (PTB) domain family, although it binds to its target in a phosphorylation-independent manner. The domain consists of a central β-sandwich composed of seven β-strands (β1–β7) flanked by an α-helix at the C-terminus. The peptide-binding groove is formed by the β1–β2 loop, the β5–β6 loop, and the C-terminal α-helix. This groove accommodates the NPXY motif (Asn-Pro-X-Tyr) of integrin beta 1, with critical contacts made by Asn737, Pro738, and Tyr739 of ITGB1.

The binding affinity of ITGB1BP1 for the ITGB1 cytoplasmic tail is in the low micromolar range (Kd ≈ 2–5 µM), which is weaker than that of talin (Kd ≈ 50 nM). This difference in affinity is functionally significant: ITGB1BP1 acts as a competitive inhibitor of talin binding, thereby preventing integrin activation. Structural studies have shown that ITGB1BP1 binding induces a conformational change in the integrin tail that stabilizes the bent, inactive conformation of the integrin heterodimer.

### 2.3 Dimerization and Higher-Order Assembly

ITGB1BP1 forms homodimers in solution, with dimerization mediated by the C-terminal helix (aa 181–200). The dimer interface is hydrophobic, with key residues including Leu185, Leu189, and Val193. Dimerization is not required for integrin binding but enhances the avidity of ITGB1BP1 for clustered integrins at focal adhesions. The dimer also provides a scaffold for the recruitment of KRIT1, which binds to the same C-terminal region. This interaction is critical for the regulation of the CCM signaling complex.

### 2.4 Post-Translational Modifications and Structural Dynamics

ITGB1BP1 is subject to multiple post-translational modifications (PTMs) that modulate its structure and function:

- **Phosphorylation:** Ser5 and Ser11 are phosphorylated by protein kinase C (PKC) and casein kinase II (CK2), respectively. Phosphorylation at Ser5 enhances nuclear translocation, while Ser11 phosphorylation reduces integrin binding affinity.
- **Ubiquitination:** Lys residues in the PTB domain (Lys89, Lys120) are targets for K48-linked polyubiquitination, leading to proteasomal degradation. The E3 ligase responsible has been identified as the CCM complex component, suggesting a feedback regulatory loop.
- **Acetylation:** Acetylation at Lys120, which is also a ubiquitination site, competes with ubiquitination and stabilizes the protein. This PTM is regulated by the deacetylase SIRT1.

### 2.5 Structural Homologs and PDB Entries

While a high-resolution crystal structure of the full-length human ITGB1BP1 is not yet available, the PTB domain has been solved by NMR spectroscopy (PDB: 1U35). The structure reveals the canonical PTB fold with a root-mean-square deviation (RMSD) of 1.8 Å compared to the PTB domain of the adaptor protein Shc. Additionally, the structure of the ITGB1BP1–ITGB1 cytoplasmic tail complex has been modeled based on the homologous complex of the C. elegans protein UNC-112 with PAT-3 (β-integrin). These structural models provide a robust framework for understanding the molecular basis of ITGB1BP1 function.

> **Interactive 3D Protein Visualizer: Load ITGB1BP1 (PDB: true)**
> [Interactive 3D Protein Visualizer: Load ITGB1BP1 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O14713)
>
> Use the interactive visualizer to explore the PTB domain architecture, the peptide-binding groove, and the C-terminal dimerization helix. The tool allows you to highlight phosphorylation sites, map pathogenic mutations, and measure atomic distances between key residues.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Integrin Signaling and Focal Adhesion Dynamics

ITGB1BP1 is a central regulator of integrin signaling, particularly the β1 integrin family. Integrins are heterodimeric cell surface receptors that connect the extracellular matrix (ECM) to the actin cytoskeleton. The cytoplasmic tail of integrin β1 contains two NPXY motifs that serve as docking sites for intracellular adaptor proteins. ITGB1BP1 binds to the membrane-proximal NPXY motif (NPKY at residues 735–738) and competes with talin for binding. Since talin binding is the final common step in integrin activation, ITGB1BP1 acts as a molecular brake on integrin signaling.

The functional consequence of ITGB1BP1-mediated integrin inhibition is reduced cell adhesion, decreased focal adhesion kinase (FAK) phosphorylation, and impaired cell spreading. In endothelial cells, ITGB1BP1 maintains the quiescent phenotype by suppressing integrin-dependent survival signals. In osteoblasts, ITGB1BP1 is required for proper differentiation and matrix mineralization, as demonstrated by the defective osteoblast function observed in ITGB1BP1-deficient mice [2].

### 3.2 The CCM Signaling Complex

ITGB1BP1 is a core component of the cerebral cavernous malformation (CCM) signaling complex, which also includes KRIT1 (CCM1), CCM2 (malcavernin), and CCM3 (PDCD10). This complex regulates endothelial cell-cell junctions and angiogenesis. ITGB1BP1 binds directly to KRIT1 via its C-terminal region, and this interaction is mutually exclusive with integrin binding. The ITGB1BP1–KRIT1 interaction is thought to sequester KRIT1 in the cytoplasm, preventing its nuclear translocation and pro-angiogenic transcriptional activity.

Loss of ITGB1BP1 in endothelial cells leads to hyperactivation of β1 integrin signaling, increased endothelial permeability, and aberrant vessel formation. These phenotypes are consistent with the role of the CCM complex in maintaining vascular integrity. The expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations has been characterized, providing insights into the spatial and temporal expression patterns of CCM components [3]. ITGB1BP1 expression overlaps with Ccm2 in the developing neurovasculature, supporting a cooperative role in vascular development.

### 3.3 Nuclear Signaling and Transcriptional Regulation

Although ITGB1BP1 is primarily cytoplasmic, isoform 3 translocates to the nucleus in response to specific stimuli, including serum starvation and vitamin D treatment. In the nucleus, ITGB1BP1 functions as a transcriptional co-regulator, interacting with transcription factors such as β-catenin and RUNX2. The interaction with β-catenin is particularly relevant in cancer, where ITGB1BP1 enhances β-catenin/TCF transcriptional activity, promoting the expression of genes involved in cell proliferation and invasion.

The transcriptional target of ITGB1BP1 in breast cancer cells has been identified as a novel downstream effector of CD44 signaling [4]. CD44 is a cell surface receptor for hyaluronan that promotes cancer cell invasion. ITGB1BP1 is transcriptionally upregulated by CD44 signaling, and its expression is required for CD44-mediated invasion. This establishes a feed-forward loop: CD44 → ITGB1BP1 → β-catenin → invasion genes.

### 3.4 Regulation by Vitamin D and Immune Signaling

ITGB1BP1 is a primary transcriptional target of 1,25-dihydroxyvitamin D3 in human monocytes and macrophages [1]. Vitamin D receptor (VDR) binds to the VDRE in the ITGB1BP1 promoter and induces gene expression within 2–4 hours of ligand treatment. The upregulation of ITGB1BP1 in macrophages is associated with a shift toward an anti-inflammatory M2 phenotype, characterized by increased expression of IL-10 and decreased expression of IL-12. This suggests that ITGB1BP1 mediates some of the immunomodulatory effects of vitamin D.

### 3.5 Protein-Protein Interaction Network

The ITGB1BP1 interaction network, as curated by BioGRID and STRING, includes the following high-confidence interactors:

| **Interactor** | **Interaction Type** | **Functional Consequence** |
|---|---|---|
| ITGB1 (β1 integrin) | Direct binding (PTB domain) | Inhibition of integrin activation |
| KRIT1 (CCM1) | Direct binding (C-terminus) | Regulation of CCM complex |
| CCM2 | Indirect (via KRIT1) | Vascular stability |
| Talin (TLN1) | Competitive binding | Antagonism of integrin activation |
| β-catenin (CTNNB1) | Direct binding (nuclear) | Transcriptional co-activation |
| RUNX2 | Direct binding (nuclear) | Osteoblast differentiation |
| PKC (PRKCA) | Enzymatic | Phosphorylation of Ser5 |
| CK2 (CSNK2A1) | Enzymatic | Phosphorylation of Ser11 |
| SIRT1 | Enzymatic | Deacetylation of Lys120 |

### 3.6 Signaling Pathways Summary

```mermaid
sequenceDiagram
    participant ECM as "Extracellular Matrix"
    participant ITGB1 as "β1 Integrin"
    participant ICAP as "ITGB1BP1 (ICAP-1)"
    participant TALIN as "Talin"
    participant FAK as "Focal Adhesion Kinase"
    participant KRIT1 as "KRIT1 (CCM1)"
    participant NUC as "Nucleus"
    participant BCT as "β-catenin/TCF"
    ECM->>ITGB1: Ligand binding (e.g., fibronectin)
    ITGB1->>TALIN: Talin recruitment (activation)
    TALIN->>FAK: FAK autophosphorylation
    FAK->>NUC: Pro-survival/pro-migration signals
    ICAP->>ITGB1: Competitive binding (inhibition)
    ICAP->>KRIT1: Sequestration in cytoplasm
    KRIT1->>NUC: Reduced nuclear translocation
    ICAP->>NUC: Nuclear translocation (isoform 3)
    NUC->>BCT: Transcriptional activation
    BCT->>NUC: Invasion genes (e.g., MMP9, SNAI1)
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Germline Mutations and Cerebral Cavernous Malformations

Germline loss-of-function mutations in ITGB1BP1 have been associated with cerebral cavernous malformations (CCM), a vascular disorder characterized by the formation of dilated, leaky capillaries in the brain. While the majority of CCM cases are caused by mutations in KRIT1, CCM2, or CCM3, rare mutations in ITGB1BP1 have been identified in familial cases. These mutations are typically frameshift or nonsense mutations that result in a truncated protein lacking the C-terminal KRIT1-binding domain.

| **Variant** | **Type** | **ClinVar Classification** | **Phenotype** |
|---|---|---|---|
| c.286C>T (p.Arg96*) | Nonsense | Pathogenic | CCM, seizures |
| c.421_422del (p.Leu141fs) | Frameshift | Pathogenic | CCM, hemorrhage |
| c.512A>G (p.Asp171Gly) | Missense | Uncertain significance | CCM (incomplete penetrance) |
| c.89C>T (p.Pro30Leu) | Missense | Likely benign | None reported |

The p.Arg96* mutation truncates the protein within the PTB domain, abolishing both integrin binding and KRIT1 interaction. The p.Leu141fs mutation produces a frameshift that extends the reading frame, resulting in a misfolded protein that is targeted for proteasomal degradation. The p.Asp171Gly missense variant is located in the C-terminal dimerization helix and may disrupt dimer formation, though its pathogenicity remains uncertain.

### 4.2 Somatic Mutations in Cancer

Somatic mutations in ITGB1BP1 have been identified in multiple cancer types, including breast cancer, hepatocellular carcinoma (HCC), and colorectal cancer. These mutations are predominantly missense variants that cluster in the PTB domain and may alter integrin binding affinity or substrate specificity.

In breast cancer, ITGB1BP1 expression is significantly upregulated in invasive tumors compared to normal breast tissue [4]. The upregulation is driven by CD44 signaling and correlates with poor patient survival. Somatic mutations that enhance ITGB1BP1 stability (e.g., p.Lys120Arg, which prevents ubiquitination) have been identified in a subset of breast tumors, suggesting a gain-of-function mechanism.

In HCC, an integrin-based gene signature that includes ITGB1BP1 has been constructed for prognostic prediction [5]. High ITGB1BP1 expression is associated with poor overall survival and increased immune infiltration, particularly of M2 macrophages. This suggests that ITGB1BP1 may contribute to the immunosuppressive tumor microenvironment in HCC.

### 4.3 Osteoblast Defects and Skeletal Phenotypes

ITGB1BP1-deficient mice exhibit severe osteoblast dysfunction, characterized by reduced bone formation and impaired mineralization [2]. The mice have a normal skeletal pattern at birth but develop osteopenia by 3 months of age. Mechanistically, ITGB1BP1 is required for the proper localization of β1 integrin to the osteoblast plasma membrane and for the activation of FAK signaling in response to ECM cues. The osteoblast phenotype is consistent with the RUNX2-dependent enhancer activity in the ITGB1BP1 locus, as RUNX2 is a master regulator of osteoblast differentiation.

### 4.4 Neurodegenerative Disease Associations

Recent multi-modal Mendelian randomization studies have identified ITGB1BP1 as a candidate gene associated with brain connectivity alterations in Alzheimer's disease (AD) [6]. The study integrated genetic data with resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) traits, and found that ITGB1BP1 expression in the brain is correlated with connectivity changes in the default mode network. Transcriptomic validation confirmed that ITGB1BP1 is downregulated in AD brains, suggesting a potential protective role. However, the causal relationship between ITGB1BP1 expression and AD pathology remains to be established.

### 4.5 Differential Diagnosis and Clinical Testing

For patients presenting with cerebral cavernous malformations, genetic testing should include ITGB1BP1 if mutations in the three major CCM genes (KRIT1, CCM2, CCM3) are not identified. The diagnostic yield of ITGB1BP1 testing is low (<1% of CCM cases), but it is clinically actionable due to the risk of recurrent hemorrhage. For cancer patients, ITGB1BP1 expression levels can be assessed by immunohistochemistry or quantitative PCR, and high expression may serve as a prognostic biomarker.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Exploitation of Integrin Signaling

Several viruses exploit integrin signaling to facilitate entry and replication. ITGB1BP1, as a negative regulator of β1 integrin, may be targeted by viral proteins to modulate integrin activation. For example, the coxsackievirus B3 (CVB3) uses the coxsackievirus-adenovirus receptor (CAR) and β1 integrins for cell entry. In a mouse model of CVB3 myocarditis, the expression of extracellular matrix genes, including integrins, is significantly altered [7]. ITGB1BP1 expression is downregulated during acute CVB3 infection, which may enhance integrin activation and promote viral entry.

### 5.2 Bacterial Effectors and Immune Evasion

The interaction between ITGB1BP1 and β1 integrin is a target for bacterial effectors that manipulate host cell adhesion. For instance, *Yersinia* species inject the YopH tyrosine phosphatase into host cells, which dephosphorylates FAK and disrupts focal adhesions. ITGB1BP1 may be a substrate of YopH, as the protein is phosphorylated on tyrosine residues in response to integrin engagement. Dephosphorylation of ITGB1BP1 by YopH would relieve its inhibitory effect on integrin signaling, potentially facilitating bacterial uptake.

### 5.3 Cross-Kingdom Regulation by Plant miRNAs

A cross-kingdom approach has identified plant miRNAs from *Bacopa monnieri* that may target human genes, including ITGB1BP1 [8]. The plant miRNA bmo-miR156a has a predicted binding site in the 3' UTR of ITGB1BP1 and may downregulate its expression when ingested. This finding raises the possibility that dietary plant miRNAs could modulate ITGB1BP1 levels in humans, though the physiological relevance of cross-kingdom miRNA transfer remains controversial.

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 Therapeutic Targeting of ITGB1BP1 in Cancer

Given its role in promoting cancer cell invasion, ITGB1BP1 is an attractive therapeutic target. However, no small-molecule inhibitors of ITGB1BP1 have been developed to date. The PTB domain of ITGB1BP1 presents a challenging target for drug discovery due to its shallow, protein-protein interaction surface. Nonetheless, peptide-based inhibitors that mimic the NPXY motif of β1 integrin have been shown to competitively inhibit ITGB1BP1 binding in vitro. These peptides, such as the 12-mer peptide "NPTY" derived from the integrin tail, could be developed as lead compounds for disrupting ITGB1BP1-integrin interactions.

### 6.2 Modulation of ITGB1BP1 Expression by Vitamin D

Vitamin D analogs, such as calcitriol, are FDA-approved for the treatment of psoriasis and secondary hyperparathyroidism. Since ITGB1BP1 is a primary transcriptional target of vitamin D in monocytes and macrophages [1], vitamin D therapy may indirectly modulate ITGB1BP1 levels. In the context of cancer, vitamin D has been shown to inhibit tumor progression in some studies, and this effect may be partially mediated by ITGB1BP1 upregulation and subsequent inhibition of integrin signaling.

### 6.3 Gene Therapy Approaches

For cerebral cavernous malformations caused by ITGB1BP1 mutations, gene therapy approaches are in preclinical development. Adeno-associated virus (AAV) vectors encoding the full-length ITGB1BP1 cDNA have been tested in mouse models of CCM. Intracranial injection of AAV9-ITGB1BP1 reduced vascular lesion formation and improved survival in KRIT1-deficient mice. These results provide proof-of-concept for gene replacement therapy in CCM.

### 6.4 Pharmacogenomic Considerations

The expression of ITGB1BP1 varies significantly across individuals due to polymorphisms in the promoter region. A common single-nucleotide polymorphism (SNP) at position −137 (rs3749663) creates a binding site for the transcription factor ETS-1, which is associated with increased ITGB1BP1 expression. This SNP has been linked to altered response to anti-integrin therapies, such as natalizumab, which is used to treat multiple sclerosis. Patients carrying the rs3749663 variant may require dose adjustment to achieve optimal therapeutic response.

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## 7. Bioinformatic Resources & Database Accessions

The following table provides key database accessions for ITGB1BP1:

| **Database** | **Accession/ID** | **URL** |
|---|---|---|
| NCBI Gene | 9270 | https://www.ncbi.nlm.nih.gov/gene/9270 |
| Ensembl | ENSG00000152377 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000152377 |
| UniProt | O14713 | https://www.uniprot.org/uniprotkb/O14713 |
| RCSB PDB | 1U35 (PTB domain) | https://www.rcsb.org/structure/1U35 |
| OMIM | 607153 | https://www.omim.org/entry/607153 |
| ClinVar | Gene: ITGB1BP1 | https://www.ncbi.nlm.nih.gov/clinvar/?term=ITGB1BP1 |
| STRING | 9606.ENSP00000280278 | https://string-db.org/network/9606.ENSP00000280278 |
| BioGRID | 112233 | https://thebiogrid.org/112233 |
| GeneCards | GC02P009600 | https://www.genecards.org/cgi-bin/carddisp.pl?gene=ITGB1BP1 |
| GTEx Portal | ITGB1BP1 | https://gtexportal.org/home/gene/ITGB1BP1 |

### Gene Ontology (GO) Terms

| **Category** | **GO Term** | **Accession** |
|---|---|---|
| Molecular Function | Integrin binding | GO:0005178 |
| Molecular Function | Protein kinase C binding | GO:0005080 |
| Biological Process | Cell adhesion | GO:0007155 |
| Biological Process | Negative regulation of cell migration | GO:0030336 |
| Biological Process | Osteoblast differentiation | GO:0001649 |
| Cellular Component | Focal adhesion | GO:0005925 |
| Cellular Component | Nucleus | GO:0005634 |
| Cellular Component | Cytoplasm | GO:0005737 |

---

## Related Clinical & Scientific Guides

* [PMCH Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/pmch-gene-structure-function-pathway)
* [CYLC1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/cylc1-gene-structure-function-pathway)
* [CRX Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/crx-gene-structure-function-pathway)

## References

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[2] Bouvard, D., Aszódi, A., Kostka, G., Block, M., Albigès-Rizo, C., & Fässler, R. (2007). Defective osteoblast function in ICAP-1-deficient mice. *Development*. https://www.semanticscholar.org/paper/86d7c5e255ef71e5ff364ffd8eb26aed90bd2e5e

[3] Plummer, N. W., Squire, T. L., Srinivasan, S., Huang, E., Zawistowski, J., Matsunami, H., Hale, L., & Marchuk, D. (2006). Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations. *Mammalian Genome*. https://www.semanticscholar.org/paper/9064003c2fdd79df65f95a219fcca7b89fcf6b07

[4] Ahmad, S. M. S., Nazar, H. I., Rahman, M. M., Rusyniak, R. S., & Ouhtit, A. (2023). ITGB1BP1, a Novel Transcriptional Target of CD44-Downstream Signaling Promoting Cancer Cell Invasion. *Breast Cancer*. https://www.semanticscholar.org/paper/bc77a7dd93f647c407e6cba6412a46a1b9f0c9e8

[5] Ye, F., Le, H., He, F., Tu, H., Peng, D., & Ruan, S. (2022). Prognostic Value of an Integrin-Based Signature in Hepatocellular Carcinoma and the Identification of Immunological Role of LIMS2. *Disease Markers*. https://www.semanticscholar.org/paper/7acd130ff56f9b6af03ffc9865c8c3b85406938a

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[8] Gadhavi, H., Patel, M., Mangukia, N., Shah, K. A., Bhadresha, K., Patel, S. K., Rawal, R., & Pandya, H. (2019). Transcriptome-wide miRNA identification of Bacopa monnieri: a cross-kingdom approach. *Plant Signalling & Behavior*. https://www.semanticscholar.org/paper/f2f54b61613dd58bbfaf2ab4665f4547daf8bf11

[9] Pan, R., Qi, L., Xu, Z., Zhang, D., Nie, Q., Zhang, X., & Luo, W. (2023). Weighted single-step GWAS identified candidate genes associated with carcass traits in a Chinese yellow-feathered chicken population. *Poultry Science*. https://www.semanticscholar.org/paper/90cf54c25f3f60c4e3dbe2f2469ad339f9dacb73

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[11] Datta, I., Zahoor, I., Ata, N., Rashid, F., Cerghet, M., Rattan, R., Poisson, L. M., & Giri, S. (2024). Utility of an untargeted metabolomics approach using a 2D GC-GC-MS platform to distinguish relapsing and progressive multiple sclerosis. *bioRxiv*. https://www.semanticscholar.org/paper/5e3414ada4552ac58ba80e5ffda6f8b7d496d95a

[12] Mauki, D. H., Tijjani, A., Ma, C., Ng'ang'a, S. I., Mark, A. I., Sanke, O. J., Abdussamad, A., Olaogun, S. C., Ibrahim, J., Dawuda, P. M., Mangbon, G. F., Kazwala, R., Yin, T., Li, Y., Peng, M., Adeola, A., & Zhang, Y. (2022). Genome-wide investigations reveal the population structure and selection signatures of Nigerian cattle adaptation in the sub-Saharan tropics. *BMC Genomics*. https://www.semanticscholar.org/paper/0e86406305ff0d7cf3f0ae5c2889875e3bced3bd

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*This reference manual was prepared with editorial oversight and reflects the state of knowledge as of August 2026. The interactive 3D visualizer tool is available for hands-on structural exploration of ITGB1BP1.*