Nephropathic infantile cystinosis

Summary

Nephropathic infantile cystinosis (MONDO:0018467) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 27

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0000124	Renal tubular dysfunction	Very frequent (80-99%)
HP:0000531	Corneal crystals	Very frequent (80-99%)
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0001941	Acidosis	Very frequent (80-99%)
HP:0001944	Dehydration	Very frequent (80-99%)
HP:0001959	Polydipsia	Very frequent (80-99%)
HP:0001969	Tubulointerstitial abnormality	Very frequent (80-99%)
HP:0001994	Renal Fanconi syndrome	Very frequent (80-99%)
HP:0002013	Vomiting	Very frequent (80-99%)
HP:0002019	Constipation	Very frequent (80-99%)
HP:0002148	Hypophosphatemia	Very frequent (80-99%)
HP:0002748	Rickets	Very frequent (80-99%)
HP:0002900	Hypokalemia	Very frequent (80-99%)
HP:0003076	Glycosuria	Very frequent (80-99%)
HP:0003109	Hyperphosphaturia	Very frequent (80-99%)
HP:0003111	Abnormal blood ion concentration	Very frequent (80-99%)
HP:0003126	Low-molecular-weight proteinuria	Very frequent (80-99%)
HP:0003355	Aminoaciduria	Very frequent (80-99%)
HP:0004918	Hyperchloremic metabolic acidosis	Very frequent (80-99%)
HP:0100511	Abnormality of vitamin D metabolism	Very frequent (80-99%)
HP:0000481	Abnormal cornea morphology	Frequent (30-79%)
HP:0000580	Pigmentary retinopathy	Frequent (30-79%)
HP:0002926	Abnormality of thyroid physiology	Frequent (30-79%)
HP:0002500	Abnormal cerebral white matter morphology	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	nephropathic infantile cystinosis
Mondo ID	MONDO:0018467
Orphanet	411629
SNOMED CT	62332007
UMLS	C3537440
MedGen	760976
GARD	0009755
Is cancer (heuristic)	no

Also known as: CTNS · cystinosis, infantile nephropathic · nephropathic infantile cystinosis

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record · 25 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn disorder of amino acid transport › nephropathic infantile cystinosis

Related subtypes (18): blue diaper syndrome, ocular cystinosis, juvenile nephropathic cystinosis, cystinuria, hyperdibasic aminoaciduria type 1, lysinuric protein intolerance, dicarboxylic aminoaciduria, Hartnup disease, histidinuria due to a renal tubular defect, iminoglycinuria, oculocerebrorenal syndrome, hypotonia-cystinuria syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, episodic ataxia type 6, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, disorder of neutral amino acid transport, autosomal recessive cerebellar ataxia - pyramidal signs - nystagmus - oculomotor apraxia syndrome, undetermined early-onset epileptic encephalopathy

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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
188834	NM_004937.3(CTNS):c.18_21del (p.Thr7fs)	CTNS	Pathogenic	criteria provided, multiple submitters, no conflicts
21442	NM_004937.3(CTNS):c.559_561+24del	CTNS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
526030	NM_004937.3(CTNS):c.971-12G>A	CTNS	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNS	HGNC:2518	ENSG00000040531	O60931	Cystinosin	gencc,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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTNS	Transporter	yes		LC_transporter, PQ-loop_rpt

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland cortex	1
right adrenal gland	1
right adrenal gland cortex	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNS	850

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNS	O60931	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 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	11420.0×	2e-04	CTNS
Miscellaneous transport and binding events	1	439.2×	0.002	CTNS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of melanin biosynthetic process	1	5617.3×	0.003	CTNS
L-cystine transport	1	2808.7×	0.003	CTNS
regulation of TORC1 signaling	1	1685.2×	0.003	CTNS
melanin biosynthetic process	1	1296.3×	0.003	CTNS
grooming behavior	1	1123.5×	0.003	CTNS
amino acid metabolic process	1	802.5×	0.004	CTNS
adult walking behavior	1	495.6×	0.005	CTNS
ATP metabolic process	1	468.1×	0.005	CTNS
long-term memory	1	421.3×	0.005	CTNS
lens development in camera-type eye	1	374.5×	0.005	CTNS
glutathione metabolic process	1	351.1×	0.005	CTNS
visual learning	1	306.4×	0.005	CTNS
positive regulation of TORC1 signaling	1	295.6×	0.005	CTNS
cognition	1	285.6×	0.005	CTNS
transmembrane transport	1	168.5×	0.007	CTNS
monoatomic ion transport	1	156.0×	0.007	CTNS
brain development	1	79.5×	0.013	CTNS
protein transport	1	43.9×	0.023	CTNS

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTNS	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CTNS	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

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

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CTNS	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.