CTNS

cystinosin, lysosomal cystine transporter, the group of Solute carrier family 66

Basic information

Region (hg38): 17:3636459-3663103

Links

ENSG00000040531 ∙ NCBI:1497 ∙ OMIM:606272 ∙ HGNC:2518 ∙ Uniprot:O60931 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cystinosis (Definitive), mode of inheritance: AR
• nephropathic cystinosis (Definitive), mode of inheritance: AR
• nephropathic cystinosis (Strong), mode of inheritance: AR
• juvenile nephropathic cystinosis (Strong), mode of inheritance: AR
• ocular cystinosis (Strong), mode of inheritance: AR
• nephropathic cystinosis (Definitive), mode of inheritance: AR
• nephropathic infantile cystinosis (Supportive), mode of inheritance: AR
• juvenile nephropathic cystinosis (Supportive), mode of inheritance: AR
• ocular cystinosis (Supportive), mode of inheritance: AR
• juvenile nephropathic cystinosis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cystinosis	AR	Biochemical; Endocrine; Ophthalmologic; Renal	Cystine-depleting agents (cysteamine) instituted at an early age can be beneficial related to manifestations affecting multiple organ systems, perhaps including cognitive development, as well as renal manifestations (renal tubular Fanconi syndrome and glomerular damage), though renal transplantation may be necessary; Surveillance for renal manifestations and related sequelae can allow early detection and management of disease with (in addition to cystine-depleting agents), replacement of renal losses; Dietary management (eg, ensuring sufficient caloric intake, and with vitamin D and phosphate supplementation) can be beneficial related to potential failure to thrive and hypophosphatemic rickets; Cysteamine eyedrops can be beneficial related to ophthalmologic sequelae; Surveillance for endocrine manifestations (eg, hypothyroidism, or hypogonadism in males) can allow early detection and medical management, including potential use of growth hormone in order to optimize height in some individuals	Biochemical; Endocrine; Musculoskeletal; Ophthalmologic; Renal	6038997; 4914142; 5443335; 406375; 333912; 7112129; 3307383; 3335962; 3550461; 3674101; 3821824; 3335962; 3185663; 3292915; 381441; 2230837; 552398; 8455682; 8172256; 7593434; 9537412; 10556299; 10417278; 10444339; 10625078; 11001803; 10673275; 12110740; 12442267; 16603246; 17643777; 19863563; 20301574; 20803298; 20814825; 21305353; 21784456; 21868618; 21371554; 21900880; 22903658; 23001048; 23462307; 23538568; 25165189

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTNS gene.

• Ocular_cystinosis (574 variants)
• Juvenile_nephropathic_cystinosis (568 variants)
• Inborn_genetic_diseases (557 variants)
• Nephropathic_cystinosis (245 variants)
• Cystinosis (117 variants)
• not_provided (57 variants)
• not_specified (26 variants)
• CTNS-related_disorder (15 variants)
• Infantile_nephropathic_cystinosis (3 variants)
• Cystinosis,_atypical_nephropathic (3 variants)
• Nephrotic_syndrome (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTNS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004937.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		5	177	3	186
missense	8	24	147	21	1	201
nonsense	14	18				32
start loss	2					2
frameshift	36	24	1			61
splice donor/acceptor (+/-2bp)	11	30			1	42
Total	72	96	153	198	5

Highest pathogenic variant AF is 0.000111386

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTNS	protein_coding	protein_coding	ENST00000381870	11	25075

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000309	0.988	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.918	271	232	1.17	0.0000162	2632
Missense in Polyphen		88	71.637	1.2284		895
Synonymous	-1.77	118	95.9	1.23	0.00000786	794
Loss of Function	2.23	9	19.7	0.458	8.78e-7	225

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000388	0.000387
Middle Eastern	0.0000544	0.0000544
South Asian	0.000196	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cystine/H(+) symporter thought to transport cystine out of lysosomes. Plays an important role in melanin synthesis, possibly by preventing melanosome acidification and subsequent degradation of tyrosinase TYR. {ECO:0000269|PubMed:22649030}.
• Disease: DISEASE: Cystinosis, adult, non-nephropathic type (CTNSANN) [MIM:219750]: A form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. Cystinosis adult non-nephropathic type is characterized by ocular features and a benign course. Patients manifest mild photophobia due to conjunctival and corneal cystine crystals. {ECO:0000269|PubMed:10625078}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cystinosis, late-onset juvenile or adolescent nephropathic type (CTNSJAN) [MIM:219900]: A form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. Late-onset juvenile or adolescent nephropathic cystinosis is an intermediated form, manifesting first at age 10 to 12 years with proteinuria due to glomerular damage rather than with the manifestations of tubular damage that occur first in infantile cystinosis. There is no excess amino aciduria and stature is normal. Photophobia, late development of pigmentary retinopathy, and chronic headaches are features. {ECO:0000269|PubMed:10444339, ECO:0000269|PubMed:12442267, ECO:0000269|PubMed:9792862}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Beta-mercaptolactate-cysteine disulfiduria;Cysteine Metabolism;Cystinosis, ocular nonnephropathic;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Miscellaneous transport and binding events (Consensus)

Recessive Scores

• pRec: 0.363

Intolerance Scores

• loftool: 0.0634
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.56

Haploinsufficiency Scores

• pHI: 0.0798
• hipred: N
• hipred_score: 0.414
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.561

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ctns
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: ctns
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: lens development in camera-type eye;cellular amino acid metabolic process;glutathione metabolic process;ion transport;brain development;long-term memory;grooming behavior;adult walking behavior;visual learning;negative regulation of hydrogen peroxide biosynthetic process;positive regulation of mitochondrial membrane potential;L-cystine transport;melanin biosynthetic process;ATP metabolic process;cognition;transmembrane transport
• Cellular component: lysosome;lysosomal membrane;early endosome;late endosome;vacuolar membrane;plasma membrane;integral component of membrane;melanosome;intracellular membrane-bounded organelle;intermediate filament cytoskeleton;extracellular exosome
• Molecular function: L-cystine transmembrane transporter activity