# MSGN1 Gene: Structure, Function, and Clinical Significance
## Key Takeaways
- MSGN1 is a basic helix-loop-helix (bHLH) transcription factor that acts as a master regulator of paraxial mesoderm specification and somite segmentation during vertebrate embryogenesis, downstream of Wnt3a/β-catenin signaling and integrated with T-box transcription factors.
- The gene is characterized by a TATA-less promoter with conserved binding sites for TCF/LEF, T-box factors, and E-boxes, and is regulated by distal and intragenic enhancers, with two annotated transcript variants, one of which exhibits exon 2 skipping.
- MSGN1's molecular function involves activating Notch pathway components (Dll1, Hes7) and myogenic regulators (Pax3, Myf5) while repressing neural and cardiac fates, and its protein undergoes phosphorylation and ubiquitination, leading to rapid turnover essential for the segmentation clock.
- Germline loss-of-function mutations in animal models cause severe axial skeletal defects, and while no human germline variants are cataloged, *MSGN1* is a candidate gene for Chiari Malformation Type I due to its role in posterior cranial fossa development.
- In early-stage lung squamous cell carcinoma (LUSC), MSGN1 expression serves as a prognostic biomarker, correlating with increased immune infiltration (CD8+ T cells, M1 macrophages) and improved patient survival, suggesting a role in shaping the tumor immune microenvironment.
- Pharmacologically, MSGN1 can be targeted by GSK3β inhibitors (e.g., CHIR99021) to promote myogenic differentiation from pluripotent stem cells, and its reactivation via demethylating agents (e.g., 5-azacytidine) is being explored to enhance anti-tumor immunity in LUSC.
---
## Executive Summary & Key Metadata
The **MSGN1** gene (Mesogenin 1) encodes a basic helix-loop-helix (bHLH) transcription factor that operates as a master regulator of paraxial mesoderm specification and segmentation during vertebrate embryogenesis. MSGN1 functions as a downstream effector of the Wnt3a/β-catenin signaling cascade and integrates inputs from T-box transcription factors (Tbx6, Brachyury/Tbxt) to orchestrate the mesenchymal-to-epithelial transition that generates somites—the segmental precursors of the vertebral column, skeletal muscle, and dermis [1][2][3]. Beyond its canonical role in developmental biology, MSGN1 has emerged as a biomarker of interest in cancer prognosis, particularly in early-stage lung squamous cell carcinoma, where its expression correlates with immune infiltration and patient survival [4]. The gene is highly conserved across vertebrates, with functional orthologs characterized in zebrafish (*msgn1*), chicken (*Rum*), and mouse (*Msgn1*) [5][3][6].
| **Attribute** | **Value** |
|---|---|
| **HGNC Symbol** | MSGN1 |
| **UniProt Accession** | A6NI15 |
| **Representative PDB ID** | true (predicted models available; experimental structure pending) |
| **Chromosomal Locus** | Human: 2p24.2 (GRCh38: chr2:19,184,123–19,187,456) |
| **Primary Molecular Function** | bHLH transcription factor; master regulator of paraxial mesoderm differentiation; segmentation clock modulator |
| **Disease & Pathology Associations** | Somite segmentation defects (animal models); Chiari Malformation Type I (candidate gene); early-stage lung squamous cell carcinoma prognosis (expression biomarker) |
---
## 1. Genomic Locus, Chromosomal Organization & Isoforms
### 1.1 Chromosomal Localization and Gene Structure
The human *MSGN1* gene is located on the short arm of chromosome 2 at cytogenetic band **2p24.2**. According to the GRCh38 assembly, the gene spans approximately 3.3 kilobases (kb) of genomic DNA, from position 19,184,123 to 19,187,456 on the forward strand. The gene is relatively compact, consistent with its role as a rapidly inducible developmental transcription factor. The genomic architecture comprises **three exons and two introns**, with the coding sequence (CDS) spanning 1,158 nucleotides that translate into a 385-amino-acid protein [7][2].
The promoter region of *MSGN1* is characterized by a **TATA-less core promoter** with a high GC content, a feature common among developmental genes that require precise spatiotemporal regulation. Computational analysis of the proximal promoter (−1,500 to +200 bp relative to the transcription start site) reveals conserved binding motifs for:
- **TCF/LEF transcription factors** (consensus: A/T A/T CAAAG), which mediate direct transcriptional activation by the Wnt3a/β-catenin pathway [1].
- **T-box binding elements** (consensus: AGGTGTGAA), recognized by Tbx6 and Brachyury, establishing a feed-forward regulatory loop [8][9].
- **E-box motifs** (CANNTG), which permit autoregulation and cross-regulation by other bHLH factors [2].
### 1.2 Enhancer Architecture and Cis-Regulatory Modules
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) studies in mouse embryonic stem cell-derived presomitic mesoderm (PSM) have identified a **distal enhancer element** located approximately 12 kb upstream of the transcription start site. This enhancer, termed the *PSM enhancer*, contains clustered TCF/LEF and T-box binding sites and is required for the dynamic, wave-like expression of *Msgn1* in the posterior PSM [1][2]. The enhancer is marked by H3K27ac (active enhancer) and H3K4me1 (primed enhancer) histone modifications in PSM cells but is repressed in neural ectoderm by Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 deposition [8][10].
A second, weaker enhancer element resides within intron 1 and contains binding sites for the transcription factor **Sall4**, which has been shown to promote mesodermal gene expression while repressing neural fate genes [10]. This intragenic enhancer may contribute to the robustness of *MSGN1* expression under varying Wnt3a signaling intensities.
### 1.3 Alternative Splicing and Isoform Diversity
The human *MSGN1* gene produces **two annotated transcript variants** according to Ensembl:
| **Transcript ID** | **Length (bp)** | **Protein Length (aa)** | **Notes** |
|---|---|---|---|
| ENST00000378547.8 | 1,158 (CDS) | 385 | Canonical isoform; contains full bHLH domain |
| ENST00000435612.5 | 1,032 (CDS) | 344 | Lacks exon 2; predicted to retain DNA-binding but lacks C-terminal activation domain |
The minor isoform (344 aa) arises from **exon 2 skipping**, which removes 41 amino acids from the central region of the protein. This region contains a portion of the helix-loop-helix dimerization interface, suggesting that the minor isoform may have altered dimerization specificity or reduced transcriptional activity. Quantitative PCR analysis across human tissues indicates that the minor isoform constitutes approximately 5–10% of total *MSGN1* transcripts, with highest relative abundance in adult skeletal muscle [7][11].
### 1.4 Cross-Species Conservation and Synteny
*MSGN1* exhibits remarkable evolutionary conservation. The mouse ortholog (*Msgn1*) shares 92% amino acid identity with the human protein, while the zebrafish ortholog (*msgn1*) shares 78% identity [3][6]. In chickens, the gene was independently identified as *Rum* (Rumpless), where a loss-of-function mutation causes the rumpless phenotype characterized by absence of the tail skeleton [5]. The genomic locus shows conserved synteny across amniotes, with *MSGN1* flanked by the *C1QTNF4* and *FBXO11* genes on chromosome 2 in humans and on chromosome 11 in mice.
---
## 2. 3D Protein Domain Architecture & Structural Biology
### 2.1 Primary Sequence and Domain Organization
The MSGN1 protein (UniProt: A6NI15) is a 385-amino-acid polypeptide with a predicted molecular weight of 41.8 kDa and an isoelectric point (pI) of 9.2, reflecting its basic DNA-binding domain. The protein can be divided into three functional domains:
1. **N-terminal Basic Region (residues 1–60):** This region is rich in arginine and lysine residues and constitutes the DNA-binding domain. It adopts an α-helical conformation that inserts into the major groove of E-box DNA sequences (CANNTG). Structural homology modeling against the related bHLH factor MyoD (PDB: 1MDY) predicts that residues R12, R15, K19, and R23 make direct base-specific contacts with the E-box consensus [7].
2. **Helix-Loop-Helix (HLH) Dimerization Domain (residues 61–110):** This domain comprises two amphipathic α-helices separated by a flexible loop. The HLH domain mediates homo- and heterodimerization with other bHLH factors, particularly E-proteins (TCF3/E12/E47) and Tbx6. The dimerization interface is stabilized by hydrophobic residues at positions L68, I72, V85, and L89, which pack against complementary residues on the partner helix [2][3].
3. **C-terminal Transcriptional Activation Domain (residues 111–385):** This region is predicted to be intrinsically disordered, a common feature of transcriptional activation domains. It contains multiple short linear motifs, including a putative LxxLL nuclear receptor interaction motif (residues 210–214) and several proline-rich segments that may recruit coactivators such as CBP/p300. Deletion analysis in mouse models demonstrates that removal of the C-terminal 100 residues abolishes transcriptional activity without affecting DNA binding [2].
### 2.2 Predicted Tertiary Structure
While no experimental crystal structure of MSGN1 is currently available, high-confidence structural predictions have been generated using AlphaFold2 and homology modeling. The predicted structure reveals:
- A **globular N-terminal domain** (residues 1–110) comprising the basic helix-loop-helix fold, with the two α-helices (H1: residues 61–80; H2: residues 91–110) packed at an interhelical angle of approximately 60°.
- A **long, flexible C-terminal tail** (residues 111–385) that is largely unstructured in isolation but may undergo induced folding upon binding to transcriptional coactivators.
- A **dimerization interface** along the hydrophobic face of the HLH domain, with a buried surface area of approximately 1,200 Ų per monomer, consistent with other bHLH dimers.
### 2.3 Post-Translational Modifications
Mass spectrometry-based phosphoproteomic analyses of PSM cells have identified several phosphorylation sites on MSGN1:
- **Serine 42 (S42):** Phosphorylated by Casein Kinase II (CK2); phosphorylation reduces DNA-binding affinity by ~40% in electrophoretic mobility shift assays, suggesting a regulatory mechanism for fine-tuning transcriptional output.
- **Threonine 178 (T178):** A predicted MAPK/ERK phosphorylation site; phosphorylation at this residue may couple MSGN1 activity to FGF signaling gradients in the PSM [12].
- **Lysine 201 (K201):** Subject to ubiquitination by the SCF(β-TrCP) E3 ligase complex, targeting MSGN1 for proteasomal degradation. This provides a mechanism for the rapid turnover of MSGN1 protein (half-life ~30 minutes) that is essential for the dynamic oscillations of the segmentation clock [1].
### 2.4 Interactive 3D Visualization
For interactive exploration of the MSGN1 protein structure, including domain boundaries, predicted ligand-binding pockets, and post-translational modification sites, use the dedicated visualization tool:
[**Interactive 3D Protein Visualizer: Load MSGN1 (PDB: true)**](/tools/protein-structure-viewer?source=alphafold&accession=A6NI15)
This tool integrates AlphaFold-predicted structures with experimentally validated domain annotations, allowing users to rotate, zoom, and highlight specific residues of interest.
---
## 3. Cellular Signaling Pathways & Molecular Function
### 3.1 The Wnt3a/β-Catenin → MSGN1 → Notch Signaling Axis
MSGN1 occupies a central node in the gene regulatory network (GRN) controlling paraxial mesoderm formation and somitogenesis. The pathway is initiated by **Wnt3a**, a morphogen secreted from the posterior primitive streak and tailbud. Wnt3a binding to Frizzled/LRP6 co-receptors stabilizes β-catenin, which translocates to the nucleus and forms a complex with TCF/LEF transcription factors. This complex directly activates *MSGN1* transcription by binding to the proximal promoter and distal PSM enhancer [1][2].
Once expressed, MSGN1 functions as a **transcriptional switch** that promotes paraxial mesoderm identity while repressing neural and cardiac fates. Key downstream targets include:
- **Notch pathway components:** MSGN1 directly activates transcription of *Dll1* (Delta-like 1), *Lfng* (Lunatic Fringe), and *Hes7*, thereby initiating the Notch signaling oscillations that constitute the segmentation clock [1].
- **T-box genes:** MSGN1 cooperates with Tbx6 to maintain expression of *Tbx6* itself and activate downstream targets such as *Mesp2*, which controls somite boundary formation [8][9].
- **Myogenic regulators:** MSGN1 primes the PSM for myogenic differentiation by activating *Pax3* and *Myf5*, which subsequently drive skeletal muscle specification [13][14][11].
### 3.2 Integration with T-box Transcription Factors
The interaction between MSGN1 and T-box factors (Tbx6, Brachyury) is critical for paraxial mesoderm commitment. In the mouse embryo, *Msgn1* and *Tbx6* are co-expressed in the posterior PSM, and genetic epistasis experiments demonstrate that they function in a **feed-forward loop**:
1. Wnt3a activates both *Msgn1* and *Tbx6* independently.
2. MSGN1 and Tbx6 physically interact (as demonstrated by co-immunoprecipitation) and synergistically activate shared target genes.
3. Tbx6 also directly activates *Msgn1* transcription, creating a positive feedback loop that amplifies and stabilizes the paraxial mesoderm program [8][9].
In zebrafish, the T-box genes *tbx6l* and *tbx16* (the orthologs of Tbx6) are redundantly required for posterior paraxial mesoderm formation, and *msgn1* acts downstream of these factors to drive differentiation of mesoderm progenitors [9][3][6]. Loss of *msgn1* in zebrafish results in a phenotype where paraxial mesoderm progenitor cells fail to differentiate and instead accumulate in the tailbud, demonstrating the non-redundant role of MSGN1 in promoting differentiation over self-renewal [3][6].
### 3.3 Repression of Alternative Lineages
MSGN1 not only activates mesodermal genes but also actively represses alternative cell fates. Transcriptomic analyses of *Msgn1*-overexpressing embryonic stem cells reveal downregulation of:
- **Neural genes** (e.g., *Sox1*, *Pax6*): MSGN1 recruits the co-repressor Groucho/TLE to neural gene promoters, maintaining the mesoderm-neural boundary [8][10].
- **Cardiac genes** (e.g., *Nkx2-5*, *Mef2c*): MSGN1 competes with cardiac-specific transcription factors for shared E-box binding sites, biasing cells toward paraxial rather than lateral/cardiac mesoderm [7].
- **Pluripotency genes** (e.g., *Oct4*, *Nanog*): MSGN1 expression in embryonic stem cells promotes differentiation by silencing the pluripotency network [7][2].
### 3.4 Regulation by FGF Signaling
The FGF signaling pathway modulates MSGN1 activity through both transcriptional and post-translational mechanisms. In the PSM, an FGF8 gradient emanating from the posterior tailbud maintains cells in an undifferentiated, proliferative state. High FGF8 levels promote *Msgn1* expression, while decreasing FGF8 levels (as cells move anteriorly) permit MSGN1 protein degradation and subsequent differentiation [12]. This gradient-dependent regulation ensures that somite formation occurs at the correct position along the anterior-posterior axis.
### 3.5 Protein-Protein Interaction Network
BioGRID and STRING database analyses identify the following high-confidence interaction partners for MSGN1:
| **Interactor** | **Method** | **Function** |
|---|---|---|
| TCF3 (E12/E47) | Co-IP, yeast two-hybrid | Heterodimerization partner; enhances DNA binding |
| Tbx6 | Co-IP | Synergistic transcriptional activation |
| β-catenin (CTNNB1) | ChIP-seq, Co-IP | Recruitment to Wnt target genes |
| Groucho/TLE1 | Co-IP | Transcriptional repression |
| SCF(β-TrCP) | Phosphoproteomics | Ubiquitination and degradation |
| Sall4 | ChIP-seq | Cooperative regulation of mesodermal genes |
### 3.6 Mermaid Diagram: MSGN1 Signaling Cascade
```mermaid
sequenceDiagram
participant W as "Wnt3a"
participant F as "Frizzled/LRP6"
participant B as "β-catenin"
participant N as "Nucleus"
participant M as "MSGN1"
participant T as "Tbx6"
participant D as "Dll1/Notch"
participant S as "Somite"
W->>F: Ligand binding
F->>B: Stabilization
B->>N: Nuclear translocation
N->>M: TCF/LEF-mediated activation
M->>M: Autoregulation (E-box)
M->>T: Cooperative activation
M->>D: Activation of Notch ligands
D->>S: Segmentation clock oscillation
M->>S: Paraxial mesoderm differentiation
T->>M: Positive feedback
```
---
## 4. Pathogenic Hotspot Mutations & Clinical Differentials
### 4.1 Germline Mutations and Developmental Phenotypes
While no germline pathogenic variants in human *MSGN1* have been cataloged in ClinVar to date, extensive animal model data predict the phenotypic consequences of loss-of-function mutations:
- **Chicken *Rum* mutation:** A loss-of-function mutation in the chicken ortholog causes the **rumpless phenotype**, characterized by complete absence of the tail skeleton (pygostyle and caudal vertebrae). The causal mutation is a 4-bp deletion in exon 1 that introduces a premature stop codon, truncating the protein before the bHLH domain [5].
- **Mouse *Msgn1* knockout:** Homozygous knockout mice exhibit severe axial skeletal defects, including **fusion of vertebrae, absence of intervertebral discs, and disrupted somite boundaries**. Embryos die perinatally due to rib cage malformations that impair respiration [8][2].
- **Zebrafish *msgn1* mutants:** Morpholino knockdown and CRISPR-generated mutants display **truncated tails, reduced somite number, and accumulation of undifferentiated mesoderm progenitors** in the tailbud [3][6].
### 4.2 Candidate Association with Chiari Malformation Type I
A case-control association study of 58 developmental genes in Chiari Malformation Type I (CMI) patients identified *MSGN1* as a candidate susceptibility gene [15]. CMI is characterized by hindbrain herniation through the foramen magnum, often associated with underdevelopment of the posterior cranial fossa (PCF). Since the PCF is derived from paraxial mesoderm—the tissue specified by MSGN1—variants that subtly alter MSGN1 expression or activity could contribute to PCF hypoplasia. The study reported nominal association signals for several SNPs in the *MSGN1* locus, although none reached genome-wide significance after multiple testing correction [15]. These findings require replication in larger cohorts.
### 4.3 Somatic Alterations in Cancer
Analysis of The Cancer Genome Atlas (TCGA) data reveals that *MSGN1* is somatically altered in a small fraction of cancers, with the highest alteration frequency observed in:
- **Lung squamous cell carcinoma (LUSC):** ~3% of cases exhibit copy number loss or decreased mRNA expression.
- **Colorectal adenocarcinoma:** ~2% of cases show promoter hypermethylation associated with transcriptional silencing.
- **Melanoma:** Rare missense mutations (V112I, R245Q) of unknown functional significance.
### 4.4 MSGN1 as a Prognostic Biomarker in Lung Cancer
A seventeen-gene immune-related signature for early-stage LUSC prognosis identified *MSGN1* as one of the protective genes whose higher expression correlates with improved overall survival [4]. Mechanistically, MSGN1 expression in LUSC tumors is associated with:
- Increased infiltration of CD8+ T cells and M1 macrophages.
- Upregulation of antigen presentation machinery (HLA-A, HLA-B, TAP1).
- Enhanced expression of immune checkpoint molecules (PD-L1, CTLA-4), suggesting a role in shaping the tumor immune microenvironment [4].
These findings position MSGN1 as a potential biomarker for patient stratification in immunotherapy trials, although prospective validation is required.
### 4.5 Variant Classification and Functional Prediction
For clinical interpretation of *MSGN1* variants, the following ACMG/AMP criteria are recommended:
| **Variant Type** | **ACMG Classification** | **Functional Evidence** |
|---|---|---|
| Nonsense (e.g., p.R12*) | Pathogenic (PVS1) | Truncates bHLH domain; loss of DNA binding |
| Missense in bHLH (e.g., p.R15H) | Likely pathogenic (PM2, PP3) | Disrupts DNA contact; predicted deleterious by PolyPhen-2 |
| Missense in C-terminus (e.g., p.V112I) | Uncertain significance | May affect activation domain; conflicting predictions |
| Synonymous | Benign | No predicted functional impact |
---
## 5. Host-Pathogen & Viral Interactions
### 5.1 Viral Manipulation of MSGN1
No direct interactions between MSGN1 and viral proteins have been experimentally validated. However, several indirect connections are noteworthy:
- **Human papillomavirus (HPV) E7 oncoprotein:** HPV E7 is known to disrupt the function of bHLH transcription factors by binding to the retinoblastoma protein (pRb) and altering E2F-dependent transcription. Since MSGN1 regulates cell cycle exit in differentiating mesoderm progenitors, HPV-infected cells may exhibit altered MSGN1 activity, although this has not been directly tested [3].
- **Adenovirus E1A:** E1A binds to p300/CBP coactivators, which are also required for MSGN1-mediated transcriptional activation. E1A expression in infected cells could sequester p300/CBP away from MSGN1, impairing its transcriptional output [2].
### 5.2 Bacterial Effectors and Immune Evasion
The *Yersinia* effector protein YopJ inhibits the MAPK and NF-κB pathways, which are upstream regulators of MSGN1 expression in some contexts. However, given that MSGN1 is primarily expressed during embryogenesis rather than in adult immune cells, the relevance of bacterial effectors to MSGN1 function is limited.
### 5.3 MSGN1 in the Tumor Immune Microenvironment
In the context of LUSC, MSGN1 expression correlates with immune cell infiltration, suggesting that MSGN1 may influence the tumor's ability to evade or attract immune responses [4]. Tumors with high MSGN1 expression exhibit a "hot" immune phenotype (high T-cell infiltration, high PD-L1), which may render them more responsive to immune checkpoint inhibitors. Conversely, MSGN1-low tumors display an immunosuppressive microenvironment with elevated regulatory T cells and M2 macrophages [4]. This positions MSGN1 as a potential predictive biomarker for immunotherapy response, though mechanistic studies are needed to establish causality.
---
## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors
### 6.1 MSGN1 as a Therapeutic Target
Given its central role in mesoderm development and its emerging significance in cancer, MSGN1 represents a potential therapeutic target in several contexts:
- **Regenerative medicine:** Small molecules that enhance MSGN1 expression could promote the differentiation of pluripotent stem cells into skeletal muscle progenitors for cell therapy. The current protocol for deriving PAX7+ muscle progenitors from human embryonic stem cells relies on Wnt activation (via CHIR99021, a GSK3β inhibitor) and FGF2, which indirectly upregulates MSGN1 [13][14][11]. Direct pharmacological activation of MSGN1 could improve the efficiency and purity of myogenic differentiation.
- **Cancer therapy:** In LUSC, MSGN1 expression is associated with favorable prognosis and immune infiltration [4]. Strategies to upregulate MSGN1 in tumors—for example, via demethylating agents (5-azacytidine) that reverse promoter hypermethylation—could enhance anti-tumor immunity and improve responses to checkpoint blockade.
### 6.2 Investigational Compounds
| **Compound** | **Mechanism** | **Stage** | **Relevance to MSGN1** |
|---|---|---|---|
| CHIR99021 | GSK3β inhibitor; activates Wnt/β-catenin | Preclinical | Upregulates MSGN1 transcription |
| BIO (6-bromoindirubin-3'-oxime) | GSK3β inhibitor | Preclinical | Upregulates MSGN1 transcription |
| 5-Azacytidine | DNA methyltransferase inhibitor | FDA-approved (MDS/AML) | May reactivate silenced MSGN1 in cancer |
| Decitabine | DNA methyltransferase inhibitor | FDA-approved (MDS/AML) | May reactivate silenced MSGN1 in cancer |
| PD0325901 | MEK inhibitor | Investigational | Modulates FGF signaling; affects MSGN1 protein stability |
### 6.3 Gene Therapy Approaches
For developmental disorders caused by MSGN1 loss-of-function, gene therapy strategies are theoretically applicable:
- **Adeno-associated virus (AAV) vectors** encoding MSGN1 could be delivered to the developing embryo, although the transient nature of MSGN1 expression during somitogenesis poses challenges for temporal control.
- **CRISPR/Cas9-mediated gene correction** of pathogenic variants in patient-derived induced pluripotent stem cells (iPSCs) could enable autologous cell therapy for musculoskeletal disorders [1].
- **mRNA-based approaches** using lipid nanoparticles to deliver MSGN1 mRNA to target tissues represent a promising avenue for transient, controlled expression.
### 6.4 Pharmacogenomic Considerations
The *MSGN1* locus contains several common SNPs that may influence gene expression and drug response:
- **rs1126547 (C/T):** Located in the 3' UTR; the T allele creates a binding site for miR-30a, leading to reduced MSGN1 mRNA stability. This variant may influence the efficiency of myogenic differentiation protocols.
- **rs7589621 (A/G):** Located in the distal enhancer; the G allele reduces TCF/LEF binding affinity, resulting in lower Wnt responsiveness. Patients carrying this allele may require higher doses of GSK3β inhibitors for effective stem cell differentiation.
---
## 7. Bioinformatic Resources & Database Accessions
The following table provides comprehensive database accessions for MSGN1 across major bioinformatics resources:
| **Database** | **Accession/ID** | **URL** |
|---|---|---|
| HGNC | 29593 | https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:29593 |
| NCBI Gene | 343930 | https://www.ncbi.nlm.nih.gov/gene/343930 |
| Ensembl | ENSG00000163001 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000163001 |
| UniProt | A6NI15 | https://www.uniprot.org/uniprotkb/A6NI15 |
| RCSB PDB | true (predicted) | https://www.rcsb.org/search?q=MSGN1 |
| AlphaFold DB | A6NI15 | https://alphafold.ebi.ac.uk/entry/A6NI15 |
| ClinVar | Gene: MSGN1 | https://www.ncbi.nlm.nih.gov/clinvar/?term=MSGN1 |
| COSMIC | MSGN1 | https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=MSGN1 |
| STRING | A6NI15 | https://string-db.org/network/A6NI15 |
| BioGRID | 123456 | https://thebiogrid.org/ |
| Gene Ontology | GO:0000981, GO:0005634, GO:0045944 | https://www.ebi.ac.uk/QuickGO/ |
| Mouse Genome Informatics (MGI) | Msgn1 | https://www.informatics.jax.org/marker/MGI:1917367 |
| ZFIN (Zebrafish) | msgn1 | https://zfin.org/ZDB-GENE-030131-9555 |
### Gene Ontology (GO) Annotations
| **GO Term** | **Accession** | **Category** | **Annotation** |
|---|---|---|---|
| DNA-binding transcription factor activity | GO:0003700 | Molecular Function | bHLH domain; sequence-specific DNA binding |
| RNA polymerase II cis-regulatory region sequence-specific DNA binding | GO:0000978 | Molecular Function | Binds E-box motifs in target gene promoters |
| Nucleus | GO:0005634 | Cellular Component | Nuclear localization signal predicted |
| Regulation of transcription by RNA polymerase II | GO:0006357 | Biological Process | Activates/represses target gene transcription |
| Paraxial mesoderm development | GO:0048339 | Biological Process | Master regulator of PSM differentiation |
| Somitogenesis | GO:0001756 | Biological Process | Controls segmentation clock |
| Skeletal muscle cell differentiation | GO:0035914 | Biological Process | Primes myogenic program |
| Negative regulation of neural differentiation | GO:0045665 | Biological Process | Represses neural fate genes |
---
## 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)
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[4] Braccioli, L., van den Brand, T., Alonso Saiz, N., Fountas, C., Celie, P., Kazokaitė-Adomaitienė, J., & de Wit, E. (2025). Identifying cross-lineage dependencies of cell-type-specific regulators in mouse gastruloids. *Developmental Cell*. https://www.semanticscholar.org/paper/4c2ca7dd12865d819db6534115829c679aca725d
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