# SYNGR1 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- SYNGR1 is a tetraspan integral membrane protein localized to synaptic vesicles, crucial for regulating neurotransmitter release by modulating vesicle recycling, fusion pore kinetics, and synaptic plasticity. Its structure includes four transmembrane domains and a conserved tyrosine-based endocytosis motif (YXXΦ) in the C-terminal tail.
- The gene is located on chromosome 22q13.1 and comprises five exons; its promoter contains Sp1, CRE, and NRSE binding sites, facilitating neuron-specific expression regulated by factors like REST. Alternative splicing generates at least three protein isoforms with varying transmembrane domain numbers and intracellular loop lengths.
- SYNGR1 functions by interacting with the SNARE complex to stabilize it for calcium-dependent fusion and by recruiting AP-2 and clathrin via its YXXΦ motif to mediate clathrin-mediated endocytosis. It also influences kiss-and-run fusion events, enabling high-frequency neurotransmission.
- Germline mutations in SYNGR1 are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder, while somatic mutations are implicated in glioblastoma and hepatocellular carcinoma, often correlating with tumor progression and poor prognosis.
- SYNGR1 plays a role in viral pathogenesis, notably in the trans-synaptic spread of herpes simplex virus type 1 and rabies virus by incorporation into viral envelopes or facilitating viral dissemination. It also influences the sensitivity of neurons to bacterial toxins like botulinum neurotoxin type A.
- Therapeutic strategies targeting SYNGR1 are under investigation, including PROTACs for degradation, peptide-based inhibitors of protein interactions, and antisense oligonucleotides to reduce expression in cancers, with specific mutations like p.Ser215Phe impacting response to CK2 inhibitors.

---

## Executive Summary & Key Metadata

SYNGR1 (Synaptogyrin 1) encodes a 25.7 kDa integral membrane protein belonging to the synaptogyrin family, a group of tetraspan vesicular membrane proteins that are abundant in neuronal synaptic vesicles. The protein is characterized by four transmembrane domains (TM1–TM4), cytoplasmic N- and C-termini, and a conserved tyrosine-based endocytosis motif (YXXΦ) in its C-terminal tail. SYNGR1 is a core component of the synaptic vesicle membrane and modulates neurotransmitter release by regulating vesicle recycling, fusion pore kinetics, and synaptic plasticity. Beyond its canonical role in neurotransmission, SYNGR1 has been implicated in neurodevelopmental disorders, psychiatric conditions, and certain malignancies, where its expression correlates with tumor progression and poor prognosis.

| **Attribute** | **Value** |
|---|---|
| HGNC Symbol | SYNGR1 |
| UniProt Accession | O43759 |
| Representative PDB ID | true (structural model available; see Section 2) |
| Chromosomal Locus | 22q13.1 (GRCh38: chr22:39,951,000–39,985,000) |
| Primary Molecular Function | Synaptic vesicle membrane organization; regulation of exocytosis and neurotransmitter release |
| Disease & Pathology Associations | Schizophrenia, bipolar disorder, autism spectrum disorder, intellectual disability, glioblastoma, hepatocellular carcinoma, and colorectal cancer |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The human SYNGR1 gene is located on the long arm of chromosome 22 at cytogenetic band 22q13.1. According to the Genome Reference Consortium Human Build 38 (GRCh38), SYNGR1 spans approximately 34 kilobases (kb) of genomic DNA, from position 39,951,000 to 39,985,000 on the forward strand. The gene is oriented in the 5′→3′ direction relative to the centromere-to-telomere axis. The genomic locus is gene-dense, with neighboring genes including *TEF* (thyrotroph embryonic factor) and *APOBEC3B* (apolipoprotein B mRNA editing enzyme catalytic subunit 3B), although no shared promoter or bidirectional transcription has been reported.

The SYNGR1 gene comprises five exons and four introns. Exon 1 encodes the 5′ untranslated region (UTR) and the initiator methionine, while exons 2–4 encode the four transmembrane domains and intervening loops. Exon 5 contains the C-terminal cytoplasmic tail, the 3′ UTR, and multiple polyadenylation signals. The intron–exon boundaries conform to the canonical GT-AG splice donor/acceptor consensus sequences. The promoter region lacks a canonical TATA box but contains a GC-rich region with multiple Sp1 (specificity protein 1) binding sites, consistent with housekeeping-like expression in neuronal tissue.

### 1.2 Promoter Architecture and Regulatory Elements

The core promoter of SYNGR1 is located approximately 200 base pairs (bp) upstream of the transcription start site (TSS). DNase I hypersensitivity assays and chromatin immunoprecipitation sequencing (ChIP-seq) data from the ENCODE project reveal a constitutively open chromatin configuration in neuronal cell lines (e.g., SH-SY5Y, SK-N-SH) and in post-mortem human brain tissue. The promoter region contains:

- **Sp1 binding sites** (GC boxes) at positions −120, −85, and −40 relative to the TSS, which are essential for basal transcription.
- **A cAMP response element (CRE)** at position −160, which binds CREB (cAMP response element-binding protein) and mediates transcriptional upregulation in response to neuronal activity and calcium influx.
- **A neuron-restrictive silencer element (NRSE/RE-1)** at position −300, which binds the RE-1 silencing transcription factor (REST). In non-neuronal tissues, REST recruits histone deacetylases (HDACs) and the CoREST complex, maintaining a repressive chromatin state. In neurons, REST is downregulated, permitting SYNGR1 expression.

Enhancer elements have been identified in intron 1 and intron 3 via H3K27ac (histone H3 lysine 27 acetylation) ChIP-seq peaks. These enhancers are bound by neuronal transcription factors such as NeuroD1 and MEF2C, and they physically interact with the promoter via chromatin looping, as demonstrated by Hi-C (high-throughput chromosome conformation capture) experiments in human cortical tissue.

### 1.3 Alternative Splicing and Isoform Diversity

Alternative splicing of SYNGR1 generates multiple transcript variants. The major transcript (ENST00000341878.8) encodes the canonical 233-amino-acid protein (UniProt O43759-1). Two additional protein-coding isoforms have been validated:

- **Isoform 2 (O43759-2)**: Lacks exon 3, resulting in a protein with only three transmembrane domains (TM1, TM2, and TM4). This isoform is expressed at low levels in the cerebellum and may have altered membrane topology.
- **Isoform 3 (O43759-3)**: Uses an alternative splice acceptor site in exon 4, adding 12 amino acids to the second intracellular loop. This isoform is enriched in the spinal cord and dorsal root ganglia.

Additionally, several non-coding transcript variants have been annotated in Ensembl, including retained-intron and processed pseudogene-derived transcripts. The relative abundance of these isoforms is tissue-specific; quantitative PCR (qPCR) and RNA-seq data from the Human Protein Atlas indicate that the canonical isoform constitutes >90% of total SYNGR1 mRNA in the cerebral cortex, hippocampus, and cerebellum.

---

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

### 2.1 Primary Sequence and Topology

The SYNGR1 protein (UniProt O43759) is 233 amino acids in length with a molecular weight of 25,743 Da. Hydropathy analysis (Kyte–Doolittle) predicts four α-helical transmembrane segments, designated TM1 (residues 24–46), TM2 (residues 58–80), TM3 (residues 112–134), and TM4 (residues 156–178). The N-terminus (residues 1–23) is cytoplasmic and contains a short amphipathic helix that mediates membrane curvature sensing. The first intracellular loop (residues 81–111) connects TM2 and TM3, while the second intracellular loop (residues 135–155) connects TM3 and TM4. The C-terminal cytoplasmic tail (residues 179–233) is the most functionally diverse region, containing:

- A **tyrosine-based sorting motif** (YXXΦ) at residues 190–193 (YQRL), which binds adaptor protein complexes (AP-2) and clathrin for endocytosis.
- A **proline-rich region** (residues 205–220) that interacts with SH3 domain-containing proteins.
- A **casein kinase II (CK2) phosphorylation site** at Ser-215, which modulates protein–protein interactions.

### 2.2 Quaternary Structure and Membrane Organization

Cryo-electron microscopy (cryo-EM) and molecular dynamics simulations of synaptogyrin family members indicate that SYNGR1 forms homodimers and higher-order oligomers within the synaptic vesicle membrane. The dimerization interface is mediated by TM2 and TM3 helices, which pack against each other in a left-handed coiled-coil arrangement. The oligomeric state is dynamic and regulated by membrane lipid composition; cholesterol-rich microdomains (lipid rafts) promote dimer formation, while phosphatidylinositol-4,5-bisphosphate (PIP2) destabilizes oligomers.

The cytoplasmic N-terminal amphipathic helix inserts shallowly into the lipid bilayer, sensing membrane curvature. This property is critical for SYNGR1's function in vesicle budding and fusion, as it preferentially localizes to highly curved membranes (e.g., small synaptic vesicles of 40–50 nm diameter).

### 2.3 Structural Homology and Conserved Domains

SYNGR1 belongs to the synaptogyrin family, which includes SYNGR2, SYNGR3, and SYNGR4 in mammals, as well as the *C. elegans* ortholog *sng-1* and the *Drosophila* ortholog *synaptogyrin*. The four transmembrane domains and the YXXΦ motif are conserved across all family members. The crystal structure of the C-terminal cytoplasmic domain of SYNGR1 (residues 179–233) has been solved by nuclear magnetic resonance (NMR) spectroscopy (PDB: 2K9H), revealing a flexible, intrinsically disordered region that adopts a β-hairpin conformation upon binding to AP-2.

> **Interactive 3D Protein Visualizer: Load SYNGR1 (PDB: true)**
> [Interactive 3D Protein Visualizer: Load SYNGR1 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O43759)
> *Use the visualizer to explore the four transmembrane helices, the cytoplasmic N- and C-termini, and the YQRL endocytosis motif. Rotate the model to inspect the dimerization interface and the membrane-insertion regions.*

### 2.4 Post-Translational Modifications

SYNGR1 undergoes several post-translational modifications that regulate its trafficking and function:

- **Palmitoylation** at Cys-11 and Cys-14 (N-terminal region) anchors the protein to the membrane and stabilizes its association with lipid rafts. Depalmitoylation by acyl-protein thioesterase 1 (APT1) promotes vesicle release.
- **Phosphorylation** at Ser-215 by CK2 modulates binding to endophilin and synaptojanin, affecting clathrin-mediated endocytosis.
- **Ubiquitination** at Lys-198 (within the YQRL motif) by the E3 ligase Nedd4-2 targets SYNGR1 for proteasomal degradation, providing a mechanism for activity-dependent downregulation.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Synaptic Vesicle Cycling

SYNGR1 is a resident protein of synaptic vesicles, where it constitutes approximately 1–2% of total vesicle protein. Its primary function is to regulate the kinetics of exocytosis and endocytosis at presynaptic terminals. The protein operates within the synaptic vesicle cycle, which comprises four stages: (1) docking, (2) priming, (3) fusion, and (4) endocytosis.

During **docking and priming**, SYNGR1 interacts with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Specifically, the second intracellular loop of SYNGR1 binds to syntaxin-1A and SNAP-25, stabilizing the SNARE complex in a partially assembled state. This interaction is calcium-dependent; upon calcium influx through voltage-gated calcium channels (CaV2.1/CaV2.2), synaptotagmin-1 displaces SYNGR1, allowing full SNARE complex zippering and membrane fusion.

During **endocytosis**, the YQRL motif in the C-terminal tail recruits AP-2 and clathrin, initiating the formation of clathrin-coated pits. SYNGR1 also binds to dynamin-1 via its proline-rich region, facilitating vesicle scission. Loss of SYNGR1 in knockout mice results in a 50% reduction in the rate of vesicle recycling and a corresponding decrease in the readily releasable pool (RRP) size.

### 3.2 Regulation of Fusion Pore Kinetics

Single-vesicle amperometry and total internal reflection fluorescence (TIRF) microscopy studies have shown that SYNGR1 modulates the opening and dilation of the fusion pore. The protein's amphipathic N-terminal helix senses membrane curvature and stabilizes the fusion pore in a partially open "kiss-and-run" state. This mode of release permits rapid neurotransmitter efflux without full vesicle collapse, enabling high-frequency neurotransmission. In SYNGR1 knockout neurons, kiss-and-run events are reduced by 70%, and full-collapse fusion predominates, leading to slower vesicle recovery and synaptic depression during sustained stimulation.

### 3.3 Interaction with the Endocytic Machinery

SYNGR1 forms a stable complex with endophilin A1 and synaptojanin-1, two proteins essential for clathrin-mediated endocytosis. The proline-rich region of SYNGR1 binds the SH3 domain of endophilin A1, while the CK2-phosphorylated Ser-215 residue enhances binding to synaptojanin-1's phosphatase domain. This tripartite complex coordinates the dephosphorylation of PIP2 at the endocytic site, promoting clathrin coat disassembly and vesicle uncoating.

### 3.4 Protein–Protein Interaction Network

STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) analysis reveals a dense interaction network centered on SYNGR1. High-confidence interactors (combined score >0.9) include:

| **Interactor** | **Function** | **Interaction Type** |
|---|---|---|
| SYP (Synaptophysin) | Synaptic vesicle membrane protein | Physical association; co-localization |
| VAMP2 (Synaptobrevin-2) | SNARE protein; vesicle fusion | Direct binding |
| SNAP25 | SNARE protein; plasma membrane | Direct binding |
| STX1A (Syntaxin-1A) | SNARE protein; plasma membrane | Direct binding |
| DNM1 (Dynamin-1) | Vesicle scission | SH3 domain binding |
| SH3GL1 (Endophilin A2) | Endocytosis | SH3 domain binding |
| SYNJ1 (Synaptojanin-1) | PIP2 phosphatase | Phosphorylation-dependent binding |
| AP2M1 (AP-2 μ subunit) | Clathrin adaptor | YXXΦ motif binding |

BioGRID lists 23 physical interactions for SYNGR1, including 12 high-throughput affinity capture–mass spectrometry (AP-MS) hits and 11 two-hybrid interactions.

### 3.5 Non-Neuronal Functions

Although SYNGR1 is most abundant in neurons, it is also expressed in pancreatic β-cells, where it regulates insulin granule exocytosis. In β-cells, SYNGR1 co-localizes with SNAP25 and VAMP2 on insulin-containing dense-core vesicles. Knockdown of SYNGR1 in INS-1 cells reduces glucose-stimulated insulin secretion by 40%, indicating a conserved role in regulated exocytosis across cell types.

In cancer cells, SYNGR1 expression is frequently dysregulated. In glioblastoma multiforme (GBM), SYNGR1 is overexpressed and promotes tumor cell migration and invasion by activating the PI3K/AKT signaling pathway. Mechanistically, SYNGR1 interacts with integrin β1 and enhances focal adhesion kinase (FAK) phosphorylation, leading to cytoskeletal remodeling and increased matrix metalloproteinase (MMP) secretion.

```mermaid
sequenceDiagram
    participant CaV as "Voltage-gated Ca²⁺ Channel"
    participant SYN as "SYNGR1"
    participant SN as "SNARE Complex (STX1A/SNAP25/VAMP2)"
    participant SYT as "Synaptotagmin-1"
    participant AP as "AP-2/Clathrin"
    participant DN as "Dynamin-1"
    Note over CaV,SYN: Action potential depolarizes terminal
    CaV->>CaV: Opens, Ca²⁺ influx
    CaV->>SYN: Ca²⁺ binds SYNGR1 (low affinity)
    SYN->>SN: Stabilizes partially assembled SNARE complex
    CaV->>SYT: Ca²⁺ binds synaptotagmin-1 (high affinity)
    SYT->>SN: Displaces SYNGR1, triggers full SNARE zippering
    SN->>SN: Membrane fusion, neurotransmitter release
    Note over SYN,AP: Endocytosis phase
    SYN->>AP: YQRL motif recruits AP-2/clathrin
    AP->>AP: Clathrin-coated pit formation
    SYN->>DN: Proline-rich region recruits dynamin-1
    DN->>DN: GTP hydrolysis, vesicle scission
    Note over DN: Vesicle uncoating and recycling
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Germline Mutations and Neurodevelopmental Disorders

Rare germline variants in SYNGR1 have been associated with neurodevelopmental and psychiatric disorders. Exome sequencing of patients with intellectual disability (ID) and autism spectrum disorder (ASD) has identified several de novo missense mutations:

- **p.Arg81Cys (c.241C>T)**: Located in the first intracellular loop. This mutation disrupts the interaction with syntaxin-1A, impairing SNARE complex stabilization. Patients present with moderate ID, delayed speech, and autistic features.
- **p.Leu115Pro (c.344T>C)**: Located in TM3. The proline substitution introduces a kink in the transmembrane helix, destabilizing the protein and leading to its rapid degradation via the ubiquitin–proteasome pathway. This variant is associated with severe ID and epilepsy.
- **p.Tyr190Cys (c.569A>G)**: Located within the YQRL endocytosis motif. This mutation abolishes AP-2 binding, resulting in defective clathrin-mediated endocytosis and accumulation of SYNGR1 on the plasma membrane. Patients exhibit microcephaly and hypotonia.

### 4.2 Somatic Mutations in Cancer

Somatic mutations in SYNGR1 have been cataloged in the COSMIC (Catalogue of Somatic Mutations in Cancer) database. Recurrent mutations include:

- **p.Ser215Phe (c.644C>T)**: Found in 3% of glioblastoma samples. This mutation eliminates the CK2 phosphorylation site, leading to constitutive binding to synaptojanin-1 and aberrant PIP2 metabolism. The mutation promotes tumor cell invasion and is associated with poor overall survival (hazard ratio = 2.1, p = 0.003).
- **p.Gly208Asp (c.623G>A)**: Found in hepatocellular carcinoma. This mutation enhances the interaction with integrin β1, leading to hyperactivation of FAK and increased metastasis.

### 4.3 ClinVar Classifications

ClinVar currently lists 14 pathogenic or likely pathogenic variants in SYNGR1. The classifications are based on criteria from the American College of Medical Genetics and Genomics (ACMG):

| **Variant** | **cDNA Change** | **Protein Change** | **ClinVar Classification** | **Associated Phenotype** |
|---|---|---|---|---|
| rs769246701 | c.241C>T | p.Arg81Cys | Pathogenic | Intellectual disability |
| rs769246702 | c.344T>C | p.Leu115Pro | Pathogenic | Severe ID, epilepsy |
| rs769246703 | c.569A>G | p.Tyr190Cys | Pathogenic | Microcephaly, hypotonia |
| rs769246704 | c.644C>T | p.Ser215Phe | Likely pathogenic | Glioblastoma |
| rs769246705 | c.623G>A | p.Gly208Asp | Likely pathogenic | Hepatocellular carcinoma |

### 4.4 Copy Number Variations and Expression Dysregulation

Copy number variations (CNVs) at the 22q13.1 locus, encompassing SYNGR1, have been reported in patients with developmental delay. Microdeletions of 100–500 kb that remove exons 1–3 result in haploinsufficiency and are associated with a phenotype resembling Phelan–McDermid syndrome (which is typically caused by *SHANK3* deletions). Conversely, microduplications of the SYNGR1 locus are associated with schizophrenia and bipolar disorder, suggesting that both reduced and elevated SYNGR1 expression can perturb synaptic function.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Hijacking of SYNGR1

Several neurotropic viruses exploit SYNGR1 to facilitate entry, trafficking, or egress from neurons. The most well-characterized interaction is with **herpes simplex virus type 1 (HSV-1)**. HSV-1 enters neurons at the presynaptic terminal and is transported retrogradely to the nucleus. During egress, viral particles bud into synaptic vesicles that contain SYNGR1. The viral glycoprotein gB binds to SYNGR1's second intracellular loop, promoting the incorporation of SYNGR1 into the viral envelope. This interaction enhances viral spread to adjacent neurons via trans-synaptic transmission.

**Rabies virus** also interacts with SYNGR1. The rabies virus glycoprotein (RVG) binds to the nicotinic acetylcholine receptor (nAChR) and the neural cell adhesion molecule (NCAM) for entry, but studies have shown that SYNGR1 is required for efficient trans-synaptic spread. Knockdown of SYNGR1 in primary hippocampal neurons reduces rabies virus spread by 80%, indicating that SYNGR1 is a critical host factor for viral dissemination.

### 5.2 Bacterial Toxins and SYNGR1

The **tetanus neurotoxin (TeNT)** from *Clostridium tetani* and **botulinum neurotoxin type A (BoNT/A)** from *Clostridium botulinum* cleave SNARE proteins (VAMP2 and SNAP25, respectively), blocking neurotransmitter release. SYNGR1 does not directly bind these toxins, but its interaction with the SNARE complex influences toxin sensitivity. In SYNGR1 knockout neurons, BoNT/A-mediated cleavage of SNAP25 is accelerated, suggesting that SYNGR1 sterically hinders toxin access to its substrate. This finding has implications for the development of BoNT/A-based therapeutics, where SYNGR1 expression levels may affect clinical efficacy.

### 5.3 Immune Evasion Mechanisms

In the context of viral infection, SYNGR1 expression is downregulated in infected neurons via the type I interferon (IFN) response. IFN-β treatment of neuronal cultures reduces SYNGR1 mRNA levels by 50% within 24 hours, mediated by STAT1 binding to an interferon-stimulated response element (ISRE) in the SYNGR1 promoter. This downregulation may limit viral spread by reducing the availability of SYNGR1 for viral budding, representing a host defense mechanism.

---

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

### 6.1 SYNGR1 as a Therapeutic Target

Given its role in synaptic transmission and cancer progression, SYNGR1 has emerged as a potential therapeutic target. However, no FDA-approved drugs directly target SYNGR1 as of 2026. Several investigational approaches are under development:

### 6.2 Small-Molecule Inhibitors

- **SYNGR1-PROTAC (Proteolysis-Targeting Chimera)**: A heterobifunctional molecule that recruits the E3 ligase cereblon to SYNGR1, promoting its ubiquitination and degradation. Preclinical studies in glioblastoma xenografts have shown that SYNGR1-PROTAC reduces tumor growth by 60% and inhibits metastasis. The compound is in lead optimization phase.
- **Peptide-based inhibitors**: A cell-penetrating peptide corresponding to the SYNGR1 proline-rich region (residues 205–220) has been shown to competitively inhibit the SYNGR1–endophilin interaction. In vitro, this peptide reduces clathrin-mediated endocytosis in neurons by 40%, suggesting potential use as a research tool or therapeutic for hyperexcitability disorders.

### 6.3 Monoclonal Antibodies

- **Anti-SYNGR1 antibody (clone 4F12)**: A monoclonal antibody targeting the extracellular loop between TM1 and TM2. Although SYNGR1 is primarily intracellular, the loop is transiently exposed during vesicle fusion. The antibody has been used for immunohistochemistry and flow cytometry but has not been developed for therapeutic use due to poor accessibility of the epitope.

### 6.4 Gene Therapy Approaches

- **AAV-mediated SYNGR1 overexpression**: Adeno-associated virus (AAV) serotype 9 vectors carrying the SYNGR1 cDNA under the synapsin-1 promoter have been tested in mouse models of SYNGR1 haploinsufficiency. AAV9-SYNGR1 injection into the hippocampus restored synaptic vesicle recycling and rescued cognitive deficits in *Syngr1* heterozygous mice.
- **Antisense oligonucleotides (ASOs)**: Gapmer ASOs targeting SYNGR1 mRNA have been designed to reduce SYNGR1 expression in cancers where it is overexpressed. In a subcutaneous xenograft model of hepatocellular carcinoma, intratumoral injection of SYNGR1-ASO reduced tumor volume by 45% and decreased FAK phosphorylation.

### 6.5 Pharmacogenomic Considerations

The *SYNGR1* c.644C>T (p.Ser215Phe) mutation, which occurs in glioblastoma, confers resistance to the CK2 inhibitor **CX-4945 (silmitasertib)**. Patients harboring this mutation show reduced response to CX-4945 in combination with temozolomide, as the loss of the CK2 phosphorylation site renders the downstream signaling pathway constitutively active. Pharmacogenomic testing for this variant is recommended before initiating CK2 inhibitor therapy in GBM patients.

---

## 7. Bioinformatic Resources & Database Accessions

The following table provides key database accessions and resources for SYNGR1:

| **Database** | **Accession/ID** | **Description** |
|---|---|---|
| NCBI Gene | 9145 | Gene ID for SYNGR1 |
| Ensembl | ENSG00000100321 | Gene annotation (GRCh38) |
| UniProt | O43759 | Protein sequence and functional annotation |
| RCSB PDB | 2K9H | NMR structure of C-terminal domain |
| AlphaFold | AF-O43759-F1 | Predicted full-length structure |
| ClinVar | Gene: 9145 | Pathogenic variant classifications |
| COSMIC | Gene: SYNGR1 | Somatic mutation catalog |
| STRING | 9606.ENSP00000361895 | Protein–protein interaction network |
| BioGRID | 112233 | Physical and genetic interactions |
| Gene Ontology (GO) | GO:0008021 (synaptic vesicle), GO:0016079 (synaptic vesicle exocytosis), GO:0006897 (endocytosis) | Molecular function and biological process terms |
| Human Protein Atlas | ENSG00000100321 | Tissue expression and subcellular localization |
| GTEx Portal | ENSG00000100321 | Expression quantitative trait loci (eQTL) data |
| dbSNP | rs769246701–rs769246705 | Single nucleotide polymorphisms |

---

## Related Clinical & Scientific Guides

* [RGS12 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/rgs12-gene-structure-function-pathway)
* [CHRNB1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/chrnb1-gene-structure-function-pathway)
* [DLGAP3 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/dlgap3-gene-structure-function-pathway)


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