Details for: CTNS

Gene ID: 1497

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: CTNS

Ensembl ID: ENSG00000040531

Description: cystinosin, lysosomal cystine transporter

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 10.12
    rCSI 9.14%
    PRS 98.12
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 10.11
    rCSI 12.25%
    PRS 86.91
  • hepatic stellate cell CL0000632
    CSI 4.54
    rCSI 17.01%
    PRS 97.17
  • suprabasal keratinocyte CL4033013
    CSI 3.86
    rCSI 6.3%
    PRS 83.65
  • helper T cell CL0000912
    CSI 3.39
    rCSI 4.79%
    PRS 94.54
  • elicited macrophage CL0000861
    CSI 2.78
    rCSI 2.56%
    PRS 99.33
  • epithelial cell CL0000066
    CSI 2.74
    rCSI 4.21%
    PRS 92.69
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.63
    rCSI 3.27%
    PRS 93.61
  • cytotoxic T cell CL0000910
    CSI 2.6
    rCSI 14.89%
    PRS 95.63
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.57
    rCSI 5.76%
    PRS 94.55
  • mesothelial cell CL0000077
    CSI 2.55
    rCSI 9.96%
    PRS 92.82
  • megakaryocyte CL0000556
    CSI 2.27
    rCSI 9.85%
    PRS 97.2
  • basal cell of epidermis CL0002187
    CSI 2.2
    rCSI 3.91%
    PRS 81.94
  • innate lymphoid cell CL0001065
    CSI 2.12
    rCSI 4.37%
    PRS 93.91
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.35
    rCSI 8.44%
    PRS 95.53
  • platelet CL0000233
    CSI 1.31
    rCSI 5.44%
    PRS 95.35
  • melanocyte of skin CL1000458
    CSI 1.23
    rCSI 1.68%
    PRS 83.04

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 [CTNS](/details-gene/1497) (cystinosin) is a protein-coding gene located on chromosome 17p13.2 that encodes cystinosin, a lysosomal cystine transporter. This protein functions as a proton/cystine symporter, responsible for transporting cystine out of the lysosome and into the cytoplasm. Loss-of-function mutations in [CTNS](/details-gene/1497) lead to the lysosomal storage disorder cystinosis, a severe autosomal recessive disease characterized by the intralysosomal accumulation of cystine crystals, leading to widespread tissue damage, particularly in the kidneys and eyes ([Link](https://doi.org/10.1038/ng0498-319)). The disease has several clinical forms, including nephropathic ([219800](https://omim.org/entry/219800)), intermediate ([219900](https://omim.org/entry/219900)), and non-nephropathic ([219750](https://omim.org/entry/219750)). Expression data indicates that [CTNS](/details-gene/1497) has a broad but significant role in a variety of cell types, with particularly high significance in hematopoietic progenitors and memory T cells, suggesting a fundamental role in cellular metabolism and maintenance across diverse lineages. ## Cellular Roles and Expression Landscape The expression profile of [CTNS](/details-gene/1497) indicates a critical and widespread function in cellular homeostasis. **Overall**, the gene shows the highest significance in hematopoietic lineages, including [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 10.12) and [megakaryocyte](/details-cell/CL0000556) (CSI: 2.27), suggesting its importance in the development and function of platelets and red blood cells. Furthermore, [CTNS](/details-gene/1497) appears to be a key gene in the immune system, with exceptionally high significance in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 10.11) and notable significance in [helper T cell](/details-cell/CL0000912) (CSI: 3.39), [cytotoxic T cell](/details-cell/CL0000910) (CSI: 2.60), and [innate lymphoid cell](/details-cell/CL0001065) (CSI: 2.12). This pattern suggests that cystine transport is fundamental for the metabolic demands of lymphocyte activation, differentiation, and long-term survival. Its role extends to myeloid cells like the [elicited macrophage](/details-cell/CL0000861) (CSI: 2.78). Beyond the hematopoietic system, [CTNS](/details-gene/1497) is significant in various structural and stromal cells, including [hepatic stellate cell](/details-cell/CL0000632) (CSI: 4.54), [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 3.86), and [basal cell of epidermis](/details-cell/CL0002187) (CSI: 2.20), as well as in the central nervous system within [astrocytes](/details-cell/CL0002605) (CSI: 2.57) and specific neuronal populations like the [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 2.63). This broad expression landscape is consistent with a housekeeping function essential for preventing lysosomal stress across multiple organ systems. ## Pathways and Molecular Function The primary molecular function of the [CTNS](/details-gene/1497) product, cystinosin, is [L-cystine transmembrane transporter activity](/details-gene/GO:0015184), specifically operating as a [solute:proton symporter](/details-gene/GO:0015295) ([Link](https://doi.org/10.1093/emboj/20.21.5940)). It is predominantly localized to the [lysosomal membrane](/details-gene/GO:0005765), but has also been found in other organelles such as the [melanosome membrane](/details-gene/GO:0033162). This transport activity is the cornerstone of its role in the [Transport of small molecules](/details-gene/R-HSA-382551) as annotated by Reactome. The biological processes associated with [CTNS](/details-gene/1497) reflect the systemic consequences of its dysfunction. Its central role is in [L-cystine transport](/details-gene/GO:0015811) and broader [amino acid metabolic processes](/details-gene/GO:0006520). The clinical manifestations of cystinosis are directly linked to GO terms such as [proximal tubule morphogenesis](/details-gene/GO:0072158) and [renal albumin absorption](/details-gene/GO:0097018), reflecting the severe renal Fanconi syndrome seen in patients. Its involvement in the [melanin biosynthetic process](/details-gene/GO:0042438) has been experimentally validated and explains the hypopigmentation observed in some patients with cystinosis ([Link](https://doi.org/10.1096/fj.11-201376)). Furthermore, its annotation in processes like [negative regulation of apoptotic process](/details-gene/GO:0043066) and [positive regulation of mitochondrial membrane potential](/details-gene/GO:0010918) suggests that cystine accumulation induces cellular stress that can lead to apoptosis and mitochondrial dysfunction, contributing to tissue damage. ## Research Directions The widespread significance of [CTNS](/details-gene/1497) across diverse cell types highlights its fundamental role in cellular health. Future research should focus on dissecting the cell-type-specific consequences of its dysfunction, beyond the well-characterized renal pathology. **Testable Hypotheses:** 1. Given the high significance of [CTNS](/details-gene/1497) in [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), its dysfunction likely impairs hematopoiesis by inducing lysosomal stress and disrupting metabolic pathways essential for differentiation, potentially contributing to the anemia and other hematological abnormalities observed in cystinosis patients. 2. The exceptionally high significance in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) suggests that [CTNS](/details-gene/1497)-mediated cystine export is critical for the metabolic reprogramming and long-term viability of memory T cells. Its absence may lead to impaired adaptive immune memory due to increased oxidative stress and mitochondrial dysfunction in these long-lived lymphocytes. **Proposed Experiment:** To test the role of [CTNS](/details-gene/1497) in memory T cell function (Hypothesis 2), one could utilize a conditional knockout mouse model where [CTNS](/details-gene/1497) is specifically deleted in T cells. Following an infection model (e.g., with Lymphocytic Choriomeningitis Virus), the formation, maintenance, and recall response of memory CD8+ T cell populations in knockout versus wild-type mice could be quantified using flow cytometry. Further *ex vivo* analysis of these cells could involve Seahorse assays to measure metabolic fitness (oxidative phosphorylation and glycolysis) and assays to quantify reactive oxygen species and apoptosis, thereby directly linking cystine accumulation to functional deficits in immune memory. **Therapeutic Potential:** [CTNS](/details-gene/1497) is a crucial therapeutic target for the monogenic disease cystinosis. As the disease is caused by a loss of function, the therapeutic strategy is not inhibition but **restoration** or **replacement** of function. The current standard of care, cysteamine, provides an alternative chemical pathway for cystine to exit the lysosome but is not a cure. Gene therapy, aimed at reintroducing a functional copy of the [CTNS](/details-gene/1497) gene into affected cells (such as hematopoietic stem cells), represents a promising curative approach and is currently under clinical investigation. Pharmacological chaperones that could help correctly fold and traffic partially functional mutant cystinosin proteins to the lysosome also represent a viable therapeutic avenue for specific mutations.

Genular Protein ID: 3658933797

Symbol: CTNS_HUMAN

Name: N/A

UniProtKB Accession Codes:

O60931 D3DTJ5 Q8IZ01 Q9UNK6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 15 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 20 EMDB 5 Ensembl 3 ExpressionAtlas 1 GO 39 Gene3D 1 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 7 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 3 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 2 Rhea 6 SMART 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9537412

Title: A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.

PubMed ID: 9537412

DOI: 10.1038/ng0498-319

PubMed ID: 10673275

Title: The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion.

PubMed ID: 10673275

DOI: 10.1101/gr.10.2.165

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

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: 10068513

Title: Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS).

PubMed ID: 10068513

DOI: 10.1006/mgme.1998.2790

PubMed ID: 28082515

Title: Impact of cystinosin glycosylation on protein stability by differential dynamic stable isotope labeling by amino acids in cell culture (SILAC).

PubMed ID: 28082515

DOI: 10.1074/mcp.m116.063867

PubMed ID: 10571941

Title: CTNS mutations in patients with cystinosis.

PubMed ID: 10571941

DOI: 10.1002/(sici)1098-1004(199912)14:6<454::aid-humu2>3.0.co;2-h

PubMed ID: 11689434

Title: Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter.

PubMed ID: 11689434

DOI: 10.1093/emboj/20.21.5940

PubMed ID: 11150305

Title: The targeting of cystinosin to the lysosomal membrane requires a tyrosine-based signal and a novel sorting motif.

PubMed ID: 11150305

DOI: 10.1074/jbc.m010562200

PubMed ID: 17897319

Title: Integral and associated lysosomal membrane proteins.

PubMed ID: 17897319

DOI: 10.1111/j.1600-0854.2007.00643.x

PubMed ID: 18337546

Title: Identification and subcellular localization of a new cystinosin isoform.

PubMed ID: 18337546

DOI: 10.1152/ajprenal.00413.2007

PubMed ID: 22649030

Title: Cystinosin is a melanosomal protein that regulates melanin synthesis.

PubMed ID: 22649030

DOI: 10.1096/fj.11-201376

PubMed ID: 22544350

Title: Distribution of cystinosin-LKG in human tissues.

PubMed ID: 22544350

DOI: 10.1007/s00418-012-0958-8

PubMed ID: 22232659

Title: Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin.

PubMed ID: 22232659

DOI: 10.1073/pnas.1115581109

PubMed ID: 25753619

Title: Lysosomal targeting of cystinosin requires AP-3.

PubMed ID: 25753619

DOI: 10.1111/tra.12277

PubMed ID: 27148969

Title: Carboxyl-terminal SSLKG motif of the human cystinosin-LKG plays an important role in plasma membrane sorting.

PubMed ID: 27148969

DOI: 10.1371/journal.pone.0154805

PubMed ID: 29467429

Title: A genetic screen for investigating the human lysosomal cystine transporter, cystinosin.

PubMed ID: 29467429

DOI: 10.1038/s41598-018-21483-x

PubMed ID: 33208952

Title: MFSD12 mediates the import of cysteine into melanosomes and lysosomes.

PubMed ID: 33208952

DOI: 10.1038/s41586-020-2937-x

PubMed ID: 36113465

Title: Structure and mechanism of human cystine exporter cystinosin.

PubMed ID: 36113465

DOI: 10.1016/j.cell.2022.08.020

PubMed ID: 9792862

Title: CTNS mutations in an American-based population of cystinosis patients.

PubMed ID: 9792862

DOI: 10.1086/302118

PubMed ID: 10482956

Title: Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation.

PubMed ID: 10482956

DOI: 10.1038/sj.ejhg.5200349

PubMed ID: 10444339

Title: Mutations of CTNS causing intermediate cystinosis.

PubMed ID: 10444339

DOI: 10.1006/mgme.1999.2876

PubMed ID: 10556299

Title: Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.

PubMed ID: 10556299

DOI: 10.1093/hmg/8.13.2507

PubMed ID: 10625078

Title: Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.

PubMed ID: 10625078

DOI: 10.1203/00006450-200001000-00007

PubMed ID: 12204010

Title: Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis.

PubMed ID: 12204010

DOI: 10.1002/humu.9063

PubMed ID: 12442267

Title: Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.

PubMed ID: 12442267

DOI: 10.1002/humu.10141

PubMed ID: 12825071

Title: Mutational spectrum of the CTNS gene in Italy.

PubMed ID: 12825071

DOI: 10.1038/sj.ejhg.5200993

PubMed ID: 15128704

Title: Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin.

PubMed ID: 15128704

DOI: 10.1093/hmg/ddh152

PubMed ID: 19852576

Title: Characterization of CTNS mutations in Arab patients with cystinosis.

PubMed ID: 19852576

DOI: 10.3109/13816810903200953

PubMed ID: 22450360

Title: Two novel CTNS mutations in cystinosis patients in Thailand.

PubMed ID: 22450360

DOI: 10.1016/j.gene.2012.03.047

PubMed ID: 21786142

Title: Genetic basis of cystinosis in Turkish patients: a single-center experience.

PubMed ID: 21786142

DOI: 10.1007/s00467-011-1942-6

Sequence Information:

  • Length: 367
  • Mass: 41738
  • Checksum: 9343889CD7576908
  • Sequence:
    • MIRNWLTIFI LFPLKLVEKC ESSVSLTVPP VVKLENGSST NVSLTLRPPL NATLVITFEI 
TFRSKNITIL ELPDEVVVPP GVTNSSFQVT SQNVGQLTVY LHGNHSNQTG PRIRFLVIRS 
SAISIINQVI GWIYFVAWSI SFYPQVIMNW RRKSVIGLSF DFVALNLTGF VAYSVFNIGL 
LWVPYIKEQF LLKYPNGVNP VNSNDVFFSL HAVVLTLIII VQCCLYERGG QRVSWPAIGF 
LVLAWLFAFV TMIVAAVGVT TWLQFLFCFS YIKLAVTLVK YFPQAYMNFY YKSTEGWSIG 
NVLLDFTGGS FSLLQMFLQS YNNDQWTLIF GDPTKFGLGV FSIVFDVVFF IQHFCLYRKR 
PGYDQLN

Genular Protein ID: 848862966

Symbol: A0A0S2Z3I9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0S2Z3I9

Database IDs:

ARBA 8 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CTD 1 ChEBI 2 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 GO 3 Gene3D 1 InterPro 2 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 Pfam 1 PhylomeDB 1 RefSeq 4 Rhea 2 SAM 3 SMART 1 SMR 1 VEuPathDB 1

Citations:

PubMed ID: 26871637

Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PubMed ID: 26871637

DOI: 10.1016/j.cell.2016.01.029

Sequence Information:

  • Length: 400
  • Mass: 45039
  • Checksum: 47AF39E14090DFC2
  • Sequence:
    • MIRNWLTIFI LFPLKLVEKC ESSVSLTVPP VVKLENGSST NVSLTLRPPL NATLVITFEI 
TFRSKNITIL ELPDEVVVPP GVTNSSFQVT SQNVGQLTVY LHGNHSNQTG PRIRFLVIRS 
SAISIINQVI GWIYFVAWSI SFYPQVIMNW RRKSVIGLSF DFVALNLTGF VAYSVFNIGL 
LWVPYIKEQF LLKYPNGVNP VNSNDVFFSL HAVVLTLIII VQCCLYERGG QRVSWPAIGF 
LVLAWLFAFV TMIVAAVGVT TWLQFLFCFS YIKLAVTLVK YFPQAYMNFY YKSTEGWSIG 
NVLLDFTGGS FSLLQMFLQS YNNDQWTLIF GDPTKFGLGV FSIVFDVVFF IQHFCLYRKR 
PGLQAARTGS GSRLRQDWAP SLQPKALPQT TSVSASSLKG

Genular Protein ID: 1457886422

Symbol: I3L4A9_HUMAN

Name: N/A

UniProtKB Accession Codes:

I3L4A9

Database IDs:

ARBA 8 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 CTD 1 ChEBI 2 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 1 GeneTree 1 HGNC 1 InterPro 2 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 PANTHER 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 3 Rhea 2 SAM 2 SMART 1 SMR 1 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: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 253
  • Mass: 28630
  • Checksum: 79F1BB80FFF3D836
  • Sequence:
    • MNWRRKSVIG LSFDFVALNL TGFVAYSVFN IGLLWVPYIK EQFLLKYPNG VNPVNSNDVF 
FSLHAVVLTL IIIVQCCLYE RGGQRVSWPA IGFLVLAWLF AFVTMIVAAV GVTTWLQFLF 
CFSYIKLAVT LVKYFPQAYM NFYYKSTEGW SIGNVLLDFT GGSFSLLQMF LQSYNNDQWT 
LIFGDPTKFG LGVFSIVFDV VFFIQHFCLY RKRPGLQAAR TGSGSRLRQD WAPSLQPKAL 
PQTTSVSASS LKG