Cystinosin
Domain
The lysosomal targeting motif, together with the second PQ-loop mediate targeting to the lysosome.
Function
Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:11689434, PubMed:15128704, PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:33208952, PubMed:36113465). Plays an important role in melanin synthesis by catalyzing cystine export from melanosomes, possibly by inhibiting pheomelanin synthesis (PubMed:22649030). In addition to cystine export, also acts as a positive regulator of mTORC1 signaling in kidney proximal tubular cells, via interactions with components of the v-ATPase and Ragulator complexes (PubMed:36113465). Also involved in small GTPase-regulated vesicle trafficking and lysosomal localization of LAMP2A, independently of cystine transporter activity (By similarity).
Involvement in disease
Cystinosis, nephropathic type
CTNS
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. The classical nephropathic form has onset in the first year of life and is characterized by a polyuro-polydipsic syndrome, marked height-weight growth delay, generalized impaired proximal tubular reabsorptive capacity, with severe fluid-electrolyte balance alterations, renal failure, ocular symptoms and other systemic complications.
None
The disease is caused by variants affecting the gene represented in this entry.
Cystinosis, adult, non-nephropathic type
CTNSANN
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Cystinosis, late-onset juvenile or adolescent nephropathic type
CTNSJAN
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the cystinosin family.
Tissue Specificity
Strongly expressed in pancreas, kidney (adult and fetal), skeletal muscle, melanocytes and keratinocytes (PubMed:22649030). Expressed at lower levels in placenta and heart. Weakly expressed in lung, liver and brain (adult and fetal) (PubMed:22649030).
Isoform 2
Represents 5-20 % of CTNS transcripts, with the exception of the testis that expresses both isoforms in equal proportions.
Cellular localization
- Isoform 1
- Lysosome membrane
- Multi-pass membrane protein
- Melanosome membrane
- Multi-pass membrane protein
- AP-3 complex is required for localization to the lysosome.
- Isoform 2
- Lysosome membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
Alternative names
Cystinosin, CTNS