Ocular cystinosis

Summary

Ocular cystinosis (MONDO:0009064) is a disease caused by CTNS (GenCC Strong), with 4 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: CTNS (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 731
• Phenotypes (HPO): 4

Clinical features

Signs & symptoms

Clinical features (HPO)

4 HPO clinical features (Orphanet curated; top 4 by frequency):

HPO ID	Term	Frequency
HP:0000505	Visual impairment	Very frequent (80-99%)
HP:0000531	Corneal crystals	Very frequent (80-99%)
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0032639	Elevated leukocyte cystine	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ocular cystinosis
Mondo ID	MONDO:0009064
MeSH	C535765
OMIM	219750
Orphanet	411641
SNOMED CT	25010000
UMLS	C2931013
MedGen	419313
GARD	0009756
Is cancer (heuristic)	no

Also known as: adult-onset cystinosis · non-nephropathic cystinosis · ocular cystinosis

Data availability: 731 ClinVar variants · 2 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › ocular cystinosis

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

285 likely benign, 142 uncertain significance, 59 pathogenic, 49 benign, 21 pathogenic/likely pathogenic, 21 conflicting classifications of pathogenicity, 20 likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1449340	NC_000017.10:g.(?3392509)(3571820_?)del	ASPA	Pathogenic	criteria provided, single submitter
1020638	NM_004937.3(CTNS):c.635C>T (p.Ala212Val)	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067346	NM_004937.3(CTNS):c.839A>G (p.Lys280Arg)	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068522	NM_004937.3(CTNS):c.140+1del	CTNS	Pathogenic	criteria provided, single submitter
1069102	NM_004937.3(CTNS):c.82_83del (p.Val28fs)	CTNS	Pathogenic	criteria provided, single submitter
1069679	NC_000017.10:g.(?3539712)(3543571_?)del	CTNS	Pathogenic	criteria provided, single submitter
1069680	NC_000017.10:g.(?3539712)(3552235_?)del	CTNS	Pathogenic	criteria provided, single submitter
1071434	NM_004937.3(CTNS):c.274C>T (p.Gln92Ter)	CTNS	Pathogenic	criteria provided, single submitter
1075103	NM_004937.3(CTNS):c.61G>T (p.Glu21Ter)	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076859	NM_004937.3(CTNS):c.735G>A (p.Trp245Ter)	CTNS	Pathogenic	criteria provided, single submitter
1179166	GRCh37/hg19 17p13.2(chr17:3539741-3561489)	CTNS	Pathogenic	no assertion criteria provided
1362222	NM_004937.3(CTNS):c.539_551del (p.Leu180fs)	CTNS	Pathogenic	criteria provided, single submitter
1391189	NM_004937.3(CTNS):c.1A>T (p.Met1Leu)	CTNS	Pathogenic	criteria provided, single submitter
1395082	NM_004937.3(CTNS):c.449G>A (p.Trp150Ter)	CTNS	Pathogenic	criteria provided, single submitter
1425663	NM_004937.3(CTNS):c.699_700del (p.Ser234fs)	CTNS	Pathogenic	criteria provided, multiple submitters, no conflicts
1451713	NM_004937.3(CTNS):c.970+5G>A	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451995	NM_004937.3(CTNS):c.668del (p.Cys223fs)	CTNS	Pathogenic	criteria provided, single submitter
1452938	NM_004937.3(CTNS):c.1000del (p.Thr334fs)	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454306	NM_004937.3(CTNS):c.27del (p.Phe9fs)	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455393	NM_004937.3(CTNS):c.922G>C (p.Gly308Arg)	CTNS	Pathogenic	criteria provided, single submitter
1456035	NC_000017.10:g.(?3550728)(3550826_?)del	CTNS	Pathogenic	criteria provided, single submitter
1457577	NM_004937.3(CTNS):c.152_153insCT (p.Ala52fs)	CTNS	Pathogenic	criteria provided, single submitter
1458479	NC_000017.10:g.(?3504346)(3561464_?)del	CTNS	Pathogenic	criteria provided, single submitter
1459518	NC_000017.11:g.3659858del	CTNS	Pathogenic	criteria provided, single submitter
1698582	NM_004937.3(CTNS):c.565C>T (p.Gln189Ter)	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705665	NM_004937.3(CTNS):c.751_752del (p.Thr251fs)	CTNS	Pathogenic	criteria provided, multiple submitters, no conflicts
1724190	NM_004937.3(CTNS):c.286C>T (p.Gln96Ter)	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188714	NM_004937.3(CTNS):c.926dup (p.Ser310fs)	CTNS	Pathogenic	criteria provided, multiple submitters, no conflicts
188718	NM_004937.3(CTNS):c.611ACG[1] (p.Asp205del)	CTNS	Pathogenic	criteria provided, multiple submitters, no conflicts
188741	NM_004937.3(CTNS):c.292dup (p.Thr98fs)	CTNS	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CTNS	Definitive	Autosomal recessive	nephropathic cystinosis	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNS	Orphanet:411629	Infantile nephropathic cystinosis
CTNS	Orphanet:411634	Juvenile nephropathic cystinosis
CTNS	Orphanet:411641	Ocular cystinosis
ASPA	Orphanet:314911	Severe Canavan disease
ASPA	Orphanet:314918	Mild Canavan disease

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNS	HGNC:2518	ENSG00000040531	O60931	Cystinosin	gencc,clinvar
TRPV1	HGNC:12716	ENSG00000196689	Q8NER1	Transient receptor potential cation channel subfamily V member 1	clinvar
CTNS-AS1	HGNC:56090	ENSG00000262903		CTNS antisense RNA 1	clinvar
ASPA	HGNC:756	ENSG00000108381	P45381	Aspartoacylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNS	Cystinosin	Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes.
TRPV1	Transient receptor potential cation channel subfamily V member 1	Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli.
ASPA	Aspartoacylase	Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.75

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	27.9×	0.101
Transporter	1	19.4×	0.101
Enzyme (other)	1	3.0×	0.392
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTNS	Transporter	yes		LC_transporter, PQ-loop_rpt
TRPV1	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TrpV1-4
CTNS-AS1	Other/Unknown	no
ASPA	Enzyme (other)	yes	3.5.1.15	Aste_AspA_hybrid_dom, Aspartoacylase, AspA/AstE_fam

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right adrenal gland cortex	2
left adrenal gland cortex	1
right adrenal gland	1
right lobe of liver	1
sural nerve	1
tibial nerve	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
corpus callosum	1
medial globus pallidus	1
nephron tubule	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNS	251	ubiquitous	marker	right adrenal gland cortex, left adrenal gland cortex, right adrenal gland
TRPV1	189	tissue_specific	yes	right lobe of liver, sural nerve, tibial nerve
CTNS-AS1	131		yes	male germ line stem cell (sensu Vertebrata) in testis, right uterine tube, right adrenal gland cortex
ASPA	238	broad	marker	corpus callosum, nephron tubule, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPV1	2,258
CTNS	850
ASPA	680
CTNS-AS1	0

Intra-cohort edges

A	B	Sources
ASPA	TRPV1	string_interaction
CTNS	TRPV1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRPV1	Q8NER1	13
ASPA	P45381	8
CTNS	O60931	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SLC-mediated transport of oligopeptides	1	3806.7×	0.002	CTNS
Aspartate and asparagine metabolism	1	346.1×	0.009	ASPA
Miscellaneous transport and binding events	1	146.4×	0.011	CTNS
TRP channels	1	135.9×	0.011	TRPV1
Metabolism of amino acids and derivatives	1	22.5×	0.052	ASPA
Metabolism	1	3.9×	0.237	ASPA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
acetate metabolic process	1	5617.3×	0.003	ASPA
response to capsazepine	1	5617.3×	0.003	TRPV1
fever generation	1	1872.4×	0.003	TRPV1
regulation of melanin biosynthetic process	1	1872.4×	0.003	CTNS
detection of temperature stimulus involved in thermoception	1	1872.4×	0.003	TRPV1
peptide secretion	1	1404.3×	0.003	TRPV1
sensory perception of mechanical stimulus	1	1404.3×	0.003	TRPV1
thermoception	1	1404.3×	0.003	TRPV1
detection of chemical stimulus involved in sensory perception of pain	1	1404.3×	0.003	TRPV1
smooth muscle contraction involved in micturition	1	1404.3×	0.003	TRPV1
chemosensory behavior	1	1123.5×	0.003	TRPV1
cellular response to alkaloid	1	1123.5×	0.003	TRPV1
L-cystine transport	1	936.2×	0.004	CTNS
aspartate metabolic process	1	702.2×	0.004	ASPA
regulation of TORC1 signaling	1	561.7×	0.005	CTNS
diet induced thermogenesis	1	468.1×	0.006	TRPV1
melanin biosynthetic process	1	432.1×	0.006	CTNS
grooming behavior	1	374.5×	0.006	CTNS
sensory perception of taste	1	374.5×	0.006	TRPV1
behavioral response to pain	1	295.6×	0.007	TRPV1
cellular response to ATP	1	295.6×	0.007	TRPV1
detection of temperature stimulus involved in sensory perception of pain	1	280.9×	0.007	TRPV1
amino acid metabolic process	1	267.5×	0.007	CTNS
cellular response to acidic pH	1	244.2×	0.007	TRPV1
calcium ion import across plasma membrane	1	181.2×	0.009	TRPV1
adult walking behavior	1	165.2×	0.010	CTNS
ATP metabolic process	1	156.0×	0.010	CTNS
long-term memory	1	140.4×	0.011	CTNS
lens development in camera-type eye	1	124.8×	0.012	CTNS
glutathione metabolic process	1	117.0×	0.012	CTNS

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 3

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TRPV1	CANNABIDIOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRPV1	19	4
CTNS	0	0
CTNS-AS1	0	0
ASPA	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANNABIDIOL	4	TRPV1
CAPSAICIN	4	TRPV1
PROPOFOL	4	TRPV1
RESINIFERATOXIN	3	TRPV1
FRAMYCETIN	3	TRPV1
ZUCAPSAICIN	3	TRPV1
CANNABINOL	3	TRPV1
ILEPCIMIDE	2	TRPV1
SB-705498	2	TRPV1
NGD-8243	2	TRPV1
MAVATREP	2	TRPV1
TETRAHYDROCANNABIVARIN	2	TRPV1
CANNABIDIVARIN	2	TRPV1
PIPERINE	2	TRPV1
CANNABIGEROL	2	TRPV1
JTS-653	2	TRPV1
OLVANIL	2	TRPV1
AMG-517	1	TRPV1
ABT-102	1	TRPV1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TRPV1	674	Binding:506, Functional:166, ADMET:2
CTNS	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ASPA	3.5.1.15	aspartoacylase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TRPV1	674

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

19 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CANNABIDIOL	4	TRPV1
CAPSAICIN	4	TRPV1
PROPOFOL	4	TRPV1
RESINIFERATOXIN	3	TRPV1
FRAMYCETIN	3	TRPV1
ZUCAPSAICIN	3	TRPV1
CANNABINOL	3	TRPV1
ILEPCIMIDE	2	TRPV1
SB-705498	2	TRPV1
NGD-8243	2	TRPV1
MAVATREP	2	TRPV1
TETRAHYDROCANNABIVARIN	2	TRPV1
CANNABIDIVARIN	2	TRPV1
PIPERINE	2	TRPV1
CANNABIGEROL	2	TRPV1
JTS-653	2	TRPV1
OLVANIL	2	TRPV1
AMG-517	1	TRPV1
ABT-102	1	TRPV1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TRPV1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	CTNS, ASPA
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CTNS-AS1

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CTNS	2	TRPV1
CTNS-AS1	0	—
ASPA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.