Details for: TRDN

Gene ID: 10345

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TRDN

Ensembl ID: ENSG00000186439

Description: triadin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • cardiac muscle cell CL0000746
    CSI 34.85
    rCSI 50%
    PRS 89.91
  • Mueller cell CL0000636
    CSI 22.43
    rCSI 51.18%
    PRS 91.55
  • regular atrial cardiac myocyte CL0002129
    CSI 17.74
    rCSI 57.09%
    PRS 92.61
  • capillary endothelial cell CL0002144
    CSI 12.09
    rCSI 22.17%
    PRS 94.08
  • ependymal cell CL0000065
    CSI 11.84
    rCSI 24.02%
    PRS 82.42
  • fast muscle cell CL0000190
    CSI 11.06
    rCSI 43.23%
    PRS 89.27
  • Schwann cell CL0002573
    CSI 10.89
    rCSI 30.95%
    PRS 92.92
  • muscle cell CL0000187
    CSI 9.77
    rCSI 20.06%
    PRS 96.06
  • adipocyte CL0000136
    CSI 8.97
    rCSI 11.51%
    PRS 90.04
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 8.42
    rCSI 31.81%
    PRS 87.74
  • macroglial cell CL0000126
    CSI 8.38
    rCSI 21.53%
    PRS 92.5
  • epicardial adipocyte CL1000309
    CSI 7.47
    rCSI 24.31%
    PRS 93.49
  • neural crest cell CL0011012
    CSI 7.22
    rCSI 5.7%
    PRS 91.59
  • cardiac neuron CL0010022
    CSI 7
    rCSI 22.4%
    PRS 94.6
  • pericyte CL0000669
    CSI 6.83
    rCSI 18.18%
    PRS 76.45
  • regular ventricular cardiac myocyte CL0002131
    CSI 6.74
    rCSI 42.11%
    PRS 90.88
  • fibroblast CL0000057
    CSI 6.7
    rCSI 19.28%
    PRS 88.08
  • cardiac endothelial cell CL0010008
    CSI 5.66
    rCSI 22.85%
    PRS 95.86
  • endocardial cell CL0002350
    CSI 4.96
    rCSI 23.76%
    PRS 93.44
  • mesothelial cell CL0000077
    CSI 4.58
    rCSI 17.91%
    PRS 85.08
  • ventricular cardiac muscle cell CL2000046
    CSI 2.99
    rCSI 10.23%
    PRS 95.95
  • macrophage CL0000235
    CSI 2.4
    rCSI 4.36%
    PRS 95.56
  • slow muscle cell CL0000189
    CSI 2.36
    rCSI 31.42%
    PRS 88.24
  • Bergmann glial cell CL0000644
    CSI 2.33
    rCSI 3.19%
    PRS 90.48
  • dopaminergic neuron CL0000700
    CSI 2.23
    rCSI 12.59%
    PRS 88.22
  • cell of skeletal muscle CL0000188
    CSI 1.88
    rCSI 20.45%
    PRS 92.72
  • mural cell CL0008034
    CSI 1.56
    rCSI 5.28%
    PRS 92.87
  • cardiac blood vessel endothelial cell CL0010006
    CSI 1.55
    rCSI 10.93%
    PRS 91.07
  • skeletal muscle satellite stem cell CL0008011
    CSI 1.17
    rCSI 5.21%
    PRS 98.08

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TRDN](/details-gene/10345) encodes Triadin, a protein primarily localized to the junctional sarcoplasmic reticulum membrane in muscle cells. Functional annotations strongly implicate [TRDN](/details-gene/10345) in the regulation of calcium ion homeostasis, which is critical for muscle contraction and cardiac conduction. Expression data confirms its central role in muscle physiology, with its most significant expression observed in [cardiac muscle cells](/details-cell/CL0000746). Research has linked mutations in [TRDN](/details-gene/10345) to cardiac arrhythmia and sudden death, highlighting its essential function in maintaining normal heart rhythm ([Link](https://doi.org/10.1093/hmg/dds104)). ## Cellular Roles and Expression Landscape The expression profile of [TRDN](/details-gene/10345) firmly establishes its role as a key component of muscle tissue. **Overall**, its significance is highest in [cardiac muscle cell](/details-cell/CL0000746) (CSI: 34.85), [regular atrial cardiac myocyte](/details-cell/CL0002129) (CSI: 17.74), and [fast muscle cell](/details-cell/CL0000190) (CSI: 11.06), underscoring its specialized function in both cardiac and skeletal muscle excitation-contraction coupling. Beyond its primary role in muscle, [TRDN](/details-gene/10345) shows notable significance in several non-muscle cell types, suggesting a broader involvement in cellular processes requiring precise calcium regulation. High significance in [Mueller cell](/details-cell/CL0000636) (CSI: 22.43), a type of retinal glial cell, and [ependymal cell](/details-cell/CL0000065) (CSI: 11.84) of the central nervous system points towards a potential role in neural tissue homeostasis. Additionally, its expression in [Schwann cells](/details-cell/CL0002573) and various neurons, including [cardiac neuron](/details-cell/CL0010022), is consistent with its function in ion channel activity and electrical signaling. The presence in [capillary endothelial cells](/details-cell/CL0002144) and [pericytes](/details-cell/CL0000669) may also indicate a role in vascular function. ## Pathways and Molecular Function The molecular functions of [TRDN](/details-gene/10345) are centered on its role as a structural and regulatory component of the calcium release unit in the sarcoplasmic reticulum. Its involvement in biological processes such as [Muscle contraction](/details-cell/GO:0006936), [Heart contraction](/details-cell/GO:0060047), and the [Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum](/details-cell/GO:0010880) is well-established. It physically interacts with other key proteins of the excitation-contraction machinery, as suggested by its annotated molecular functions, including [Protein binding](/details-cell/GO:0005515) and [Transmembrane transporter binding](/details-cell/GO:0044325). These functions are integral to several major physiological pathways. [TRDN](/details-gene/10345) is a key participant in the Reactome pathways for [Muscle contraction](/details-pathway/R-HSA-397014) and [Cardiac conduction](/details-pathway/R-HSA-5576891). Its localization to the [Junctional sarcoplasmic reticulum membrane](/details-cell/GO:0014701) places it at the critical interface where electrical signals are transduced into calcium release, a process fundamental to cellular excitability in muscle and nerve cells. This is consistent with its high expression in [cardiac muscle cells](/details-cell/CL0000746), which rely on this mechanism for rhythmic contraction. ## Research Directions The established link between [TRDN](/details-gene/10345) deficiency and lethal cardiac arrhythmias provides a clear direction for research, while its unexpected expression in non-muscle cells opens new avenues of investigation. Based on the available data, several testable hypotheses can be proposed: 1. Disease-associated mutations in [TRDN](/details-gene/10345) disrupt its protein-protein interactions within the junctional sarcoplasmic reticulum complex, specifically with the ryanodine receptor and calsequestrin, leading to aberrant calcium sparks and arrhythmogenesis in [cardiac muscle cells](/details-cell/CL0000746). 2. In retinal [Mueller cells](/details-cell/CL0000636), [TRDN](/details-gene/10345) participates in a calcium signaling complex that regulates glial cell function, such as potassium siphoning or neurotransmitter uptake, and its dysregulation could contribute to retinal pathologies. To test the first hypothesis, a specific experimental approach could be employed. One could generate human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) harboring patient-specific [TRDN](/details-gene/10345) mutations using CRISPR-Cas9 genome editing. The impact on cardiac function could be assessed by measuring calcium handling dynamics with fluorescent calcium indicators and recording action potentials using multi-electrode arrays. Concurrently, co-immunoprecipitation followed by mass spectrometry in these cells would identify altered binding partners and quantify the reduced interaction with known components of the calcium release unit. Given that loss-of-function mutations in [TRDN](/details-gene/10345) cause severe disease, it is not a suitable target for inhibition. Instead, its therapeutic potential lies in strategies aimed at restoring its function. For monogenic arrhythmia syndromes caused by [TRDN](/details-gene/10345) deficiency, gene replacement therapy could represent a potential long-term curative strategy. However, the systemic importance of calcium homeostasis suggests that any therapeutic intervention would require high specificity to avoid off-target effects in skeletal muscle and other tissues where the gene is expressed.

Genular Protein ID: 2916413452

Symbol: TRDN_HUMAN

Name: Triadin

UniProtKB Accession Codes:

Q13061 A5D6W5 F5H2W7 Q6NSB8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 28 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 3 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7588753

Title: Molecular cloning of the cDNA encoding human skeletal muscle triadin and its localisation to chromosome 6q22-6q23.

PubMed ID: 7588753

DOI: 10.1111/j.1432-1033.1995.258_1.x

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15485681

Title: Calsequestrin mutant D307H exhibits depressed binding to its protein targets and a depressed response to calcium.

PubMed ID: 15485681

DOI: 10.1016/j.cardiores.2004.09.009

PubMed ID: 22422768

Title: Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human.

PubMed ID: 22422768

DOI: 10.1093/hmg/dds104

PubMed ID: 24325401

Title: Distinct regions of triadin are required for targeting and retention at the junctional domain of the sarcoplasmic reticulum.

PubMed ID: 24325401

DOI: 10.1042/bj20130719

Sequence Information:

  • Length: 729
  • Mass: 81595
  • Checksum: 0D9653203D52FA05
  • Sequence:
    • MTEITAEGNA STTTTVIDSK NGSVPKSPGK VLKRTVTEDI VTTFSSPAAW LLVIALIITW 
SAVAIVMFDL VDYKNFSASS IAKIGSDPLK LVRDAMEETT DWIYGFFSLL SDIISSEDEE 
DDDGDEDTDK GEIDEPPLRK KEIHKDKTEK QEKPERKIQT KVTHKEKEKG KEKVREKEKP 
EKKATHKEKI EKKEKPETKT LAKEQKKAKT AEKSEEKTKK EVKGGKQEKV KQTAAKVKEV 
QKTPSKPKEK EDKEKAAVSK HEQKDQYAFC RYMIDIFVHG DLKPGQSPAI PPPLPTEQAS 
RPTPASPALE EKEGEKKKAE KKVTSETKKK EKEDIKKKSE KETAIDVEKK EPGKASETKQ 
GTVKIAAQAA AKKDEKKEDS KKTKKPAEVE QPKGKKQEKK EKHVEPAKSP KKEHSVPSDK 
QVKAKTERAK EEIGAVSIKK AVPGKKEEKT TKTVEQEIRK EKSGKTSSIL KDKEPIKGKE 
EKVPASLKEK EPETKKDEKM SKAGKEVKPK PPQLQGKKEE KPEPQIKKEA KPAISEKVQI 
HKQDIVKPEK TVSHGKPEEK VLKQVKAVTI EKTAKPKPTK KAEHREREPP SIKTDKPKPT 
PKGTSEVTES GKKKTEISEK ESKEKADMKH LREEKVSTRK ESLQLHNVTK AEKPARVSKD 
VEDVPASKKA KEGTEDVSPT KQKSPISFFQ CVYLDGYNGY GFQFPFTPAD RPGESSGQAN 
SPGQKQQGQ

Genular Protein ID: 537378250

Symbol: Q8IVK2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8IVK2

Database IDs:

ARBA 10 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 6 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SAM 2

Citations:

PubMed ID: 12659871

Title: Human skeletal muscle triadin: gene organization and cloning of the major isoform, Trisk 51.

PubMed ID: 12659871

DOI: 10.1016/S0006-291X(03)00406-6

Sequence Information:

  • Length: 461
  • Mass: 51555
  • Checksum: 076A535EF502B28A
  • Sequence:
    • MTEITAEGNA STTTTVIDSK NGSVPKSPGK VLKRTVTEDI VTTFSSPAAW LLVIALIITW 
SAVAIVMFDL VDYKNFSASS IAKIGSDPLK LVRDAMEETT DWIYGFFSLL SDIISSEDEE 
DDDGDEDTDK GEIDEPPLRK KEIHKDKTEK QEKPERKIQT KVTHKEKEKG KEKVREKEKP 
EKKATHKEKI EKKEKPETKT VAKEQKKAKT AEKSEEKTKK EVKGGKQEKV KQTAAKVKEV 
QKTPSKPKEK EDKEKAAVSK HEQKDQYAFC RYMIDIFVHG DLKPGQSPAI PPPLPTEQAS 
RPTPASPALE EKEGEKKKAE KKVTSETKKK AEKEDIKKKS EKETAIDVEK KEPGKASETK 
QGTVKIAAQA AAKKDEKKED SKKTKKPAEV EQPKGKKQEK KEKHVEPAKS PKKEHSVPSD 
KQVKAKTERA KEEIGAVSSK KAVPGKKEEK TTKTVEQGKK K

Genular Protein ID: 3428095542

Symbol: A0A590UJV0_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A590UJV0

Database IDs:

ARBA 10 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 2 GeneTree 1 HGNC 1 InterPro 2 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 2 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 461
  • Mass: 51595
  • Checksum: 5142335EF038C250
  • Sequence:
    • MTEITAEGNA STTTTVIDSK NGSVPKSPGK VLKRTVTEDI VTTFSSPAAW LLVIALIITW 
SAVAIVMFDL VDYKNFSASS IAKIGSDPLK LVRDAMEETT DWIYGFFSLL SDIISSEDEE 
DDDGDEDTDK GEIDEPPLRK KEIHKDKTEK QEKPERKIQT KVTHKEKEKG KEKVREKEKP 
EKKATHKEKI EKKEKPETKT LAKEQKKAKT AEKSEEKTKK EVKGGKQEKV KQTAAKVKEV 
QKTPSKPKEK EDKEKAAVSK HEQKDQYAFC RYMIDIFVHG DLKPGQSPAI PPPLPTEQAS 
RPTPASPALE EKEGEKKKAE KKVTSETKKK AEKEDIKKKS EKETAIDVEK KEPGKASETK 
QGTVKIAAQA AAKKDEKKED SKKTKKPAEV EQPKGKKQEK KEKHVEPAKS PKKEHSVPSD 
KQVKAKTERA KEEIGAVSIK KAVPGKKEEK TTKTVEQGKK K

Genular Protein ID: 770445776

Symbol: H9ME53_HUMAN

Name: N/A

UniProtKB Accession Codes:

H9ME53

Database IDs:

ARBA 10 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 GO 2 GeneTree 1 HGNC 1 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 2 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 22422768

Title: Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human.

PubMed ID: 22422768

DOI: 10.1093/hmg/dds104

Sequence Information:

  • Length: 286
  • Mass: 32127
  • Checksum: E436694661F1502F
  • Sequence:
    • MTEITAEGNA STTTTVIDSK NGSVPKSPGK VLKRTVTEDI VTTFSSPAAW LLVIALIITW 
SAVAIVMFDL VDYKNFSASS IAKIGSDPLK LVRDAMEETT DWIYGFFSLL SDIISSEDEE 
DDDGDEDTDK GEIDEPPLRK KEIHKDKTEK QEKPERKIQT KVTHKEKEKG KEKVREKEKP 
EKKATHKEKI EKKEKPETKT LAKEQKKAKT AEKSEEKTKK EVKGGKQEKV KQTAAKVKEV 
QKTPSKPKEK EDKEKAAVSK HEQKGKHSEQ EAAGGSKRIL GKKHMQ