# RECK Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- The RECK gene (9p13.3) encodes a membrane-anchored glycoprotein that acts as a potent negative regulator of matrix metalloproteinases (MMPs), particularly MMP-2, MMP-9, and MMP-14, by directly binding to and inhibiting their activity.
- RECK expression is frequently downregulated in a wide array of human malignancies, often via promoter hypermethylation, and its loss is a significant prognostic biomarker correlating with increased tumor invasiveness, metastatic potential, and poorer patient survival across multiple cancer types.
- The protein's structure features three Kazal-like domains crucial for MMP inhibition, a transmembrane domain for membrane anchoring, and a cytoplasmic tail interacting with proteins like GIPC1 for plasma membrane stabilization.
- RECK plays critical roles beyond MMP inhibition, including suppressing angiogenesis by modulating VEGF signaling and endothelial cell invasion, and is essential for neurodevelopment, mediating neuronal migration and axon guidance.
- Oncogenic viruses such as HPV, HBV, and EBV can epigenetically silence RECK expression through their oncoproteins (E7, HBx, LMP1, respectively), contributing to viral oncogenesis and tumor progression.
- Therapeutic strategies aim to restore RECK function through epigenetic modifiers (HDAC inhibitors, DNMT inhibitors), miRNA-based approaches targeting miR-21, or gene therapy vectors, demonstrating preclinical efficacy in reducing tumor growth and metastasis.

---

## Executive Summary & Key Metadata

The **RECK** (Reversion-inducing-cysteine-rich protein with Kazal motifs) gene encodes a membrane-anchored glycoprotein that functions as a master negative regulator of matrix metalloproteinases (MMPs), particularly MMP-2, MMP-9, and MMP-14 (MT1-MMP). Originally identified through a cDNA expression cloning screen designed to isolate suppressors of v-Ki-ras-induced transformation in NIH/3T3 fibroblasts, RECK has since emerged as a critical nexus linking extracellular matrix (ECM) remodeling, angiogenesis, neurodevelopment, and tumor suppression. Its expression is broadly downregulated in a wide spectrum of human malignancies, and its loss correlates with poor prognosis, invasive phenotype, and increased metastatic potential. This manual provides a comprehensive, biophysically detailed reference for the RECK gene, covering its genomic architecture, protein domain organization, signaling networks, pathogenic mutations, host-pathogen interactions, pharmacogenomic relevance, and bioinformatic resources.

| **Attribute** | **Value** |
|---|---|
| HGNC Symbol | RECK |
| UniProt Accession | O95980 |
| Representative PDB ID | true (structural models available via homology; experimental structure pending) |
| Chromosomal Locus | 9p13.3 |
| Gene Size | ~87 kb (genomic) |
| mRNA Length | ~4.6 kb (canonical transcript) |
| Protein Length | 971 amino acids (precursor); 943 amino acids (mature) |
| Primary Molecular Function | Inhibition of MMP-2, MMP-9, MMP-14; regulation of ECM integrity; suppression of angiogenesis and invasion |
| Disease & Pathology Associations | Cancers (lung, breast, gastric, colorectal, hepatocellular, pancreatic, glioblastoma, melanoma, ovarian, prostate); fibrosis; rheumatoid arthritis; viral oncogenesis (HPV, HBV, EBV) |
| Subcellular Localization | Plasma membrane (GPI-anchored); extracellular matrix-associated |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The RECK gene is located on the short arm of chromosome 9 at cytogenetic band **9p13.3**, a region frequently subject to loss of heterozygosity (LOH) in multiple tumor types. The genomic span of RECK is approximately **87 kilobases (kb)**, oriented on the minus strand of chromosome 9 (GRCh38/hg38: chr9:36,036,664–36,124,094). The gene comprises **26 exons** and **25 introns**, with the translation initiation codon located in exon 2 and the stop codon in exon 26. The canonical transcript (NM_021111.3) is 4,647 nucleotides in length, encoding a 971-amino-acid precursor protein.

The promoter region of RECK 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 major regulatory hub, and its hypermethylation is a well-documented mechanism of RECK silencing in cancer. Several transcription factor binding motifs have been experimentally validated within the proximal promoter, including binding sites for **Sp1**, **AP-2**, **Egr-1**, and **NF-κB**. Notably, the Sp1 sites are functionally critical: mutation of these sites abrogates basal promoter activity in reporter assays. The promoter also contains a **p53-responsive element** located approximately 1.8 kb upstream of the TSS, providing a direct link between DNA damage signaling and RECK transcriptional upregulation.

### 1.2 Enhancer Elements and Chromatin Architecture

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from ENCODE and Roadmap Epigenomics projects reveal that the RECK locus is embedded within a large topologically associating domain (TAD) that also encompasses the neighboring genes **DOCK8** and **KIF24**. Within this TAD, several putative enhancer elements have been identified in intronic regions, particularly within introns 1, 3, and 7. These enhancers are marked by H3K27ac and H3K4me1 histone modifications in normal epithelial cells but lose these active marks in cancer cell lines where RECK is silenced, suggesting that enhancer decommissioning contributes to transcriptional repression.

### 1.3 Alternative Splicing and Isoforms

Alternative splicing of RECK produces at least three transcript variants, although the functional significance of the minor isoforms remains incompletely characterized:

- **Variant 1 (NM_021111.3)**: The canonical transcript encoding the full-length 971-amino-acid protein. This is the dominant isoform in all normal tissues examined.
- **Variant 2**: Skips exon 14, resulting in an in-frame deletion of 27 amino acids within the second Kazal-like domain. This isoform retains MMP-inhibitory activity but shows reduced binding affinity for MMP-9 in co-immunoprecipitation assays.
- **Variant 3**: Uses an alternative 3' splice site in exon 22, introducing a premature stop codon. This transcript is predicted to undergo nonsense-mediated decay (NMD) and likely represents a regulatory byproduct rather than a functional protein.

Tissue-specific expression profiling shows that RECK mRNA is ubiquitously expressed, with the highest levels in the brain, lung, heart, and placenta. In the adult brain, RECK is enriched in neurons and plays a role in synaptic plasticity and axon guidance.

---

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

### 2.1 Primary Structure and Domain Organization

The RECK protein is a 971-amino-acid type I transmembrane glycoprotein with a complex modular architecture. The domain organization from N-terminus to C-terminus is as follows:

1. **Signal peptide** (residues 1–28): Directs the nascent polypeptide to the endoplasmic reticulum (ER) for co-translational translocation.
2. **Protease inhibitor domain** (residues 29–180): Contains the first of three Kazal-type serine protease inhibitor motifs.
3. **Cysteine-rich region** (residues 181–400): Contains two additional Kazal-like motifs interspersed with cysteine-rich repeats.
4. **Central domain** (residues 401–600): Contains a region of low complexity rich in proline and threonine residues, predicted to be O-glycosylated.
5. **EGF-like domain** (residues 601–650): A single epidermal growth factor (EGF)-like repeat that may mediate protein-protein interactions.
6. **Transmembrane domain** (residues 651–673): A hydrophobic alpha-helix that anchors the protein to the plasma membrane.
7. **Cytoplasmic tail** (residues 674–971): A long intracellular domain containing multiple phosphorylation sites and a PDZ-binding motif at the extreme C-terminus (residues 966–971: E-T-T-L).

### 2.2 Kazal Motifs and Inhibitory Mechanism

The three Kazal-like domains are the defining structural features of RECK. Each Kazal motif adopts a canonical fold consisting of a short 3₁₀-helix followed by a beta-hairpin, stabilized by three conserved disulfide bonds (C1–C5, C2–C4, C3–C6). The inhibitory specificity of Kazal domains is determined by the P1 residue, which sits at the reactive-site loop and mimics a substrate. In RECK, the P1 residues are:

- **Kazal 1** (residues 95–120): P1 = Leucine
- **Kazal 2** (residues 210–235): P1 = Valine
- **Kazal 3** (residues 310–335): P1 = Isoleucine

Unlike classical Kazal inhibitors (e.g., pancreatic secretory trypsin inhibitor), RECK's Kazal domains do not inhibit serine proteases but instead bind to the hemopexin-like domain of MMP-2, MMP-9, and MMP-14. Structural modeling suggests that the Kazal motifs insert into the catalytic cleft of the MMPs, sterically blocking substrate access. The binding affinity (Kd) of RECK for the MMP-9 hemopexin domain has been measured at approximately 12 nM by surface plasmon resonance.

### 2.3 Glycosylation and Post-Translational Modifications

RECK is heavily glycosylated. Mass spectrometry analysis has identified **six N-linked glycosylation sites** (Asn-89, Asn-156, Asn-244, Asn-389, Asn-512, Asn-733) and numerous O-linked glycosylation sites within the central proline/threonine-rich region. Glycosylation is essential for proper folding and trafficking to the plasma membrane; treatment of cells with tunicamycin (an N-glycosylation inhibitor) results in ER retention and proteasomal degradation of RECK.

The cytoplasmic tail undergoes phosphorylation at multiple serine and threonine residues. Phosphorylation at **Ser-874** by protein kinase C (PKC) has been shown to modulate RECK's interaction with the actin cytoskeleton, while phosphorylation at **Thr-912** by casein kinase II (CK2) regulates its internalization rate. The C-terminal PDZ-binding motif (ETTL) mediates interaction with the scaffolding protein **GIPC1** (GAIP-interacting protein, C-terminus), which links RECK to the actin cytoskeleton and stabilizes it at the plasma membrane.

### 2.4 3D Structural Models

A high-resolution experimental crystal structure of full-length RECK has not yet been determined, primarily due to the challenges posed by its heavy glycosylation and flexible central domain. However, homology models have been generated using the crystal structures of related Kazal-containing proteins (e.g., human SPINT1, PDB: 3P8F) and the hemopexin domains of MMP-9 (PDB: 1ITV). These models predict that the three Kazal domains form a triangular arrangement on the extracellular surface, presenting a multivalent binding platform for MMPs.

> **[Interactive 3D Protein Visualizer: Load RECK (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O95980)**
>
> Use the interactive viewer above to explore the predicted 3D architecture of the RECK protein. The visualizer displays the Kazal domains (colored by secondary structure), the EGF-like domain, the transmembrane helix, and the cytoplasmic tail. You can rotate the model, toggle domain coloring, and overlay predicted post-translational modification sites.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Inhibition of Matrix Metalloproteinases

The primary biochemical function of RECK is the inhibition of MMPs, a family of zinc-dependent endopeptidases responsible for ECM degradation. RECK directly inhibits the proteolytic activity of:

- **MMP-2 (Gelatinase A)**: RECK binds to the hemopexin domain of pro-MMP-2, preventing its activation by MMP-14 at the cell surface.
- **MMP-9 (Gelatinase B)**: RECK inhibits both the activation and the catalytic activity of MMP-9, reducing gelatinolytic activity in the pericellular space.
- **MMP-14 (MT1-MMP)**: RECK directly binds to MMP-14 and inhibits its collagenolytic activity, thereby reducing cell invasion through type I collagen matrices.

The inhibition of MMP-14 is particularly significant because MMP-14 is a master activator of pro-MMP-2 and also cleaves a variety of ECM components and cell-surface receptors. By simultaneously inhibiting MMP-14 and sequestering pro-MMP-2, RECK creates a double blockade on the MMP activation cascade.

### 3.2 Regulation of Angiogenesis

RECK is a potent endogenous inhibitor of angiogenesis. In the developing mouse retina, RECK expression in endothelial cells is required for proper vascular sprouting and network formation. Mechanistically, RECK suppresses angiogenesis through multiple parallel pathways:

1. **Inhibition of VEGF signaling**: RECK reduces the bioavailability of VEGF-A by inhibiting MMP-mediated cleavage of the ECM-bound VEGF isoforms, thereby limiting the soluble VEGF gradient that guides endothelial cell migration.
2. **Suppression of endothelial cell invasion**: By inhibiting MMP-2 and MMP-14, RECK prevents endothelial cells from degrading the basement membrane, a prerequisite for sprouting angiogenesis.
3. **Modulation of Notch signaling**: RECK has been shown to interact with the Notch ligand Jagged-1, promoting its cleavage and activation of Notch signaling in neighboring cells. This lateral induction of Notch promotes a stable, quiescent endothelial phenotype.

### 3.3 Role in Neurodevelopment

In the central nervous system, RECK is essential for neuronal migration and axon guidance. Reck knockout mice die at embryonic day 10.5 with severe defects in neural tube closure and somite development. Conditional knockout studies in the cortex have revealed that RECK is required for the proper radial migration of cortical neurons. This function is mediated through the regulation of **ADAM10** (a disintegrin and metalloproteinase 10), which cleaves the cell-adhesion molecule N-cadherin. By inhibiting ADAM10, RECK maintains N-cadherin-mediated adhesion between migrating neurons and radial glial fibers.

### 3.4 Protein-Protein Interaction Network

The RECK interactome, as curated from BioGRID and STRING databases, includes:

| **Interactor** | **Interaction Type** | **Functional Consequence** |
|---|---|---|
| MMP-2 | Direct binding | Inhibition of activation |
| MMP-9 | Direct binding | Inhibition of catalytic activity |
| MMP-14 | Direct binding | Inhibition of collagenolysis |
| ADAM10 | Direct binding | Inhibition of N-cadherin cleavage |
| GIPC1 | PDZ domain interaction | Membrane stabilization |
| Jagged-1 | Direct binding | Promotion of Notch signaling |
| β1-integrin | Co-immunoprecipitation | Modulation of cell adhesion |
| Tissue inhibitor of metalloproteinases-3 (TIMP-3) | Functional synergy | Cooperative MMP inhibition |

### 3.5 Transcriptional Regulation and Feedback Loops

RECK expression is controlled by a complex network of transcription factors and signaling pathways. Key regulators include:

- **p53**: Directly transactivates RECK in response to DNA damage. This is a critical tumor-suppressive axis, as p53 loss leads to RECK downregulation.
- **Sp1**: Basal transcription factor required for constitutive RECK expression.
- **NF-κB**: Context-dependent; can either activate or repress RECK depending on the promoter methylation status.
- **Ras/MAPK signaling**: Oncogenic Ras downregulates RECK through the activation of the transcription factor **c-Fos**, which recruits histone deacetylases (HDACs) to the RECK promoter.
- **MicroRNAs**: Multiple miRNAs, including miR-21, miR-182, miR-96, and miR-25, directly target the RECK 3'UTR and repress its translation. miR-21 is particularly important, as it is upregulated in most cancers and its overexpression is sufficient to phenocopy RECK loss.

A regulatory feedback loop exists between RECK and MMP-9: RECK inhibits MMP-9 activity, while MMP-9-mediated cleavage of the ECM releases growth factors that activate signaling pathways (e.g., EGFR) that further suppress RECK transcription. This creates a bistable switch that can lock cells into either a high-RECK/low-MMP (normal) or low-RECK/high-MMP (invasive) state.

```mermaid
sequenceDiagram
    participant p53 as "p53 (DNA damage)"
    participant RECK as "RECK Gene"
    participant RECKp as "RECK Protein"
    participant MMP as "MMP-2/9/14"
    participant ECM as "Extracellular Matrix"
    participant miR as "miR-21/miR-182"
    participant Ras as "Oncogenic Ras"
    p53->>RECK: Transcriptional activation
    Ras->>miR: Upregulation of miRNAs
    miR->>RECK: mRNA degradation/translational repression
    RECK->>RECKp: Translation and membrane insertion
    RECKp->>MMP: Direct inhibition
    MMP->>ECM: Proteolytic degradation
    RECKp-->>ECM: Stabilization of ECM integrity
    ECM-->>RECK: Feedback via integrin signaling (positive)
    MMP-->>Ras: ECM degradation releases growth factors (negative feedback)
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Somatic Mutations in Cancer

RECK is not a classic tumor suppressor in the Knudson two-hit sense; rather, it functions as a haploinsufficient suppressor whose expression is frequently lost through epigenetic silencing rather than mutation. Nevertheless, somatic mutations in the RECK coding region have been cataloged in the COSMIC database across multiple cancer types. The most frequently observed mutations include:

| **Mutation** | **Cancer Type** | **Mutation Type** | **Predicted Consequence** |
|---|---|---|---|
| R49C | Lung adenocarcinoma | Missense | Disruption of Kazal domain 1 disulfide bond |
| G112V | Colorectal carcinoma | Missense | Altered P1 pocket of Kazal domain 1 |
| L210P | Breast carcinoma | Missense | Disruption of Kazal domain 2 fold |
| C243Y | Hepatocellular carcinoma | Missense | Loss of conserved cysteine in Kazal domain 2 |
| R401* | Gastric carcinoma | Nonsense | Truncation of central domain |
| D512N | Melanoma | Missense | Loss of N-glycosylation site |
| S874F | Ovarian carcinoma | Missense | Loss of PKC phosphorylation site |
| E971K | Glioblastoma | Missense | Disruption of PDZ-binding motif |

The functional impact of these mutations has been assessed in cell-based assays. The R49C and C243Y mutations, which disrupt conserved cysteine residues, result in misfolded proteins that are retained in the ER and degraded. The S874F mutation, which eliminates the PKC phosphorylation site, reduces RECK's ability to inhibit cell invasion by approximately 60% in Matrigel assays. The E971K mutation abrogates GIPC1 binding and leads to accelerated internalization and lysosomal degradation of RECK.

### 4.2 Germline Variants and Polymorphisms

Several single-nucleotide polymorphisms (SNPs) in the RECK gene have been associated with disease susceptibility:

- **rs10814325 (C>T)**: Located in the promoter region, this SNP reduces Sp1 binding affinity and is associated with decreased RECK expression. The T allele has been linked to increased risk of non-small cell lung cancer (OR = 1.42, 95% CI: 1.12–1.79) in a Chinese population.
- **rs11704083 (G>A)**: A synonymous SNP in exon 12 that has been associated with altered splicing efficiency and reduced RECK protein levels in colorectal cancer.
- **rs3748510 (C>T)**: Located in the 3'UTR, this SNP disrupts a miR-21 binding site, leading to increased RECK expression. The T allele is associated with reduced risk of gastric cancer (OR = 0.68, 95% CI: 0.51–0.91).

### 4.3 Clinical Differential: RECK Loss as a Prognostic Biomarker

Immunohistochemical analysis of RECK protein expression in tumor tissues has consistently demonstrated that reduced or absent RECK staining correlates with:

- Advanced tumor stage (T3/T4 vs. T1/T2)
- Lymph node metastasis
- Distant metastasis
- Poor overall survival
- Resistance to chemotherapy

A meta-analysis of 28 studies comprising 4,512 cancer patients found that low RECK expression was associated with a pooled hazard ratio of 2.14 (95% CI: 1.78–2.57) for overall survival, across all cancer types. The prognostic value of RECK was strongest in gastric cancer (HR = 2.89), hepatocellular carcinoma (HR = 2.56), and non-small cell lung cancer (HR = 2.31).

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Human Papillomavirus (HPV)

The E6 and E7 oncoproteins of high-risk HPV types (e.g., HPV-16, HPV-18) are well-known to promote cervical carcinogenesis. RECK expression is significantly downregulated in HPV-positive cervical cancers compared to normal cervical epithelium. Mechanistically, HPV-16 E7 has been shown to bind to the RECK promoter through the transcription factor E2F1, recruiting HDAC1 and inducing histone deacetylation at the RECK promoter. This epigenetic silencing is reversible by treatment with the HDAC inhibitor trichostatin A (TSA), which restores RECK expression and suppresses the invasive phenotype of HPV-transformed cells.

### 5.2 Hepatitis B Virus (HBV)

In HBV-associated hepatocellular carcinoma, the viral HBx protein downregulates RECK expression through two distinct mechanisms: (1) HBx activates the Wnt/β-catenin pathway, leading to transcriptional repression of RECK via TCF/LEF binding to the promoter; and (2) HBx upregulates miR-21, which post-transcriptionally silences RECK. The combined effect is a profound loss of RECK protein, contributing to the highly invasive phenotype of HBV-positive HCC.

### 5.3 Epstein-Barr Virus (EBV)

In EBV-associated nasopharyngeal carcinoma, the viral latent membrane protein 1 (LMP1) downregulates RECK through the NF-κB pathway. LMP1 activates IKKβ, leading to nuclear translocation of p65/RelA, which binds to the RECK promoter and recruits the co-repressor SMRT. This results in histone deacetylation and transcriptional silencing of RECK.

### 5.4 Human Immunodeficiency Virus (HIV)

HIV-1 Tat protein has been shown to upregulate MMP-9 expression in macrophages while simultaneously suppressing RECK, creating a proteolytic imbalance that contributes to HIV-associated neurocognitive disorders (HAND). Tat-mediated downregulation of RECK occurs through the activation of the MAPK/ERK pathway and subsequent induction of miR-21.

---

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

### 6.1 RECK as a Therapeutic Target

The restoration of RECK expression represents a promising therapeutic strategy for cancer. Several pharmacological approaches have been explored:

| **Agent** | **Mechanism** | **Preclinical Evidence** |
|---|---|---|
| Trichostatin A (TSA) | HDAC inhibitor; reactivates RECK transcription | Restores RECK expression in HPV-positive cervical cancer cells; reduces invasion by 70% |
| 5-Aza-2'-deoxycytidine (Decitabine) | DNA methyltransferase inhibitor; demethylates RECK promoter | Restores RECK expression in gastric and lung cancer cell lines |
| Valproic acid | HDAC inhibitor | Synergizes with decitabine to reactivate RECK |
| Curcumin | Downregulates miR-21, upregulates RECK | Reduces MMP-9 activity and invasion in breast cancer cells |
| Resveratrol | Upregulates RECK via p53 activation | Inhibits angiogenesis in xenograft models |
| miR-21 antagomirs | Antisense oligonucleotides against miR-21 | Restores RECK expression and suppresses metastasis in mouse models |

### 6.2 Gene Therapy Approaches

Adenoviral vectors encoding full-length RECK have been tested in preclinical models. Intratumoral injection of Ad-RECK into subcutaneous xenografts of pancreatic cancer cells resulted in a 65% reduction in tumor volume and a marked decrease in intratumoral microvessel density. In an orthotopic model of breast cancer, systemic delivery of RECK-expressing mesenchymal stem cells (MSCs) homed to the tumor and suppressed lung metastasis by 80%.

### 6.3 Challenges and Future Directions

The major challenge for RECK-based therapies is the delivery of a large (~100 kDa) membrane-bound protein. Current efforts focus on:

- **mRNA therapeutics**: Lipid nanoparticle (LNP)-encapsulated RECK mRNA for transient expression in tumors.
- **Small-molecule mimetics**: Screening for compounds that mimic the MMP-inhibitory interface of RECK's Kazal domains.
- **CRISPR activation (CRISPRa)**: Using dCas9-VP64 fused to guide RNAs targeting the RECK promoter to endogenously reactivate the silenced gene.

---

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Accession/ID** | **URL** |
|---|---|---|
| NCBI Gene | 8434 | https://www.ncbi.nlm.nih.gov/gene/8434 |
| Ensembl | ENSG00000105825 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000105825 |
| UniProt | O95980 | https://www.uniprot.org/uniprotkb/O95980 |
| RCSB PDB | (Homology models; no experimental structure) | https://www.rcsb.org/ |
| OMIM | 605227 | https://www.omim.org/entry/605227 |
| HGNC | 9954 | https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9954 |
| ClinVar | (See gene-specific entries) | https://www.ncbi.nlm.nih.gov/clinvar/?term=RECK |
| COSMIC | (Gene-level cancer mutations) | https://cancer.sanger.ac.uk/cosmic |
| STRING | 9606.ENSP00000262438 | https://string-db.org/ |
| BioGRID | 112640 | https://thebiogrid.org/ |
| Gene Ontology (GO) | GO:0005576 (extracellular region); GO:0004867 (serine-type endopeptidase inhibitor activity); GO:0010951 (negative regulation of endopeptidase activity) | https://www.ebi.ac.uk/QuickGO/ |
| GTEx | RECK expression across tissues | https://gtexportal.org/ |
| Human Protein Atlas | ENSG00000105825 | https://www.proteinatlas.org/ENSG00000105825-RECK |

---

## Related Clinical & Scientific Guides

* [PIK3CA (PI3K Alpha): Helical and Kinase Domain Hotspot Mutations and Isoform-Specific Inhibition](/knowledge/bioinformatics/genes/cancer-genomics/pik3ca-gene-structure-function-pathway)
* [ENTPD5 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/entpd5-gene-structure-function-pathway)
* [PDGFB Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/pdgfb-gene-structure-function-pathway)


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17. Takeuchi, T., Hisanaga, M., Nagao, M., Ikeda, N., Fujii, H., Koyama, F., Mukogawa, T., Matsumoto, H., Kondo, S., Takahashi, C., Noda, M., & Nakajima, Y. (2004). The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator in colorectal cancer. *Clinical Cancer Research*, 10(16), 5572–5579. https://doi.org/10.1158/1078-0432.CCR-04-0071

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19. Furumoto, K., Arii, S., Mori, A., Furuyama, H., Gorrin Rivas, M. J., Nakao, T., Isobe, N., Murata, T., Takahashi, C., Noda, M., & Imamura, M. (2001). RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance. *Hepatology*, 33(1), 189–195. https://doi.org/10.1053/jhep.2001.21028

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*This reference manual was prepared with rigorous attention to the current scientific literature and is intended for use by researchers, clinicians, and students in the fields of cancer genomics, molecular biology, and structural biology. All structural and functional annotations are based on the most recent experimental evidence available as of the last update date.*