Uridine-cytidineuria

Summary

Uridine-cytidineuria (MONDO:0032773) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	uridine-cytidineuria
Mondo ID	MONDO:0032773
OMIM	618477
UMLS	C4760647
MedGen	1681582
GARD	0025739
Is cancer (heuristic)	no

Also known as: URCTU · uridine-cytidineuria

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › uridine-cytidineuria

Related subtypes (92): thiopurine metabolic disease, hypercalcemia, infantile, hypermanganesemia with dystonia, abdominal obesity-metabolic syndrome, plasma protein metabolism disease, inherited lipid metabolism disorder, lysosomal storage disease, striatonigral degeneration, inborn metal metabolism disorder, inborn vitamin metabolic disorder, chondrocalcinosis 2, Ehlers-Danlos syndrome, spondylodysplastic type, fish eye disease, aromatase excess syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, hypertriglyceridemia 1, autosomal dominant myoglobinuria, diastrophic dysplasia, hemolytic anemia due to diphosphoglycerate mutase deficiency, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, inherited threoninemia, inborn glycerol kinase deficiency, achondrogenesis type IB, diabetes mellitus, noninsulin-dependent, 1, diabetes mellitus, noninsulin-dependent, 2, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, diabetes mellitus, noninsulin-dependent, 3, hypercholesterolemia, familial, 4, hypoalphalipoproteinemia, primary, 1, autosomal recessive proximal renal tubular acidosis, diabetes mellitus, noninsulin-dependent, 4, normophosphatemic familial tumoral calcinosis, apolipoprotein c-III deficiency, hypotonia-failure to thrive-microcephaly syndrome, chondrodysplasia with joint dislocations, gPAPP type, gluthathione peroxidase deficiency, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diabetes mellitus, noninsulin-dependent, 5, congenital disorder of glycosylation, monogenic diabetes, 2-hydroxyglutaric aciduria, familial hypoparathyroidism, familial intrahepatic cholestasis, inborn aminoacylase deficiency, disorder of lysosomal-related organelles, inborn disorder of porphyrin metabolism, disorder of metabolite absorption and transport, autosomal dominant proximal renal tubular acidosis, neurodegeneration with brain iron accumulation, ferro-cerebro-cutaneous syndrome, familial hypocalciuric hypercalcemia, hypophosphatasia, hereditary amyloidosis, peroxisomal disease, inborn disorder of amino acid and other organic acid metabolism, inborn carbohydrate metabolic disorder, inborn disorder of energy metabolism, inborn disorder of biogenic amine metabolism and transport, inborn disorder of purine or pyrimidine metabolism, spondyloepimetaphyseal dysplasia, PAPSS2 type, hereditary lipodystrophy, hereditary recurrent myoglobinuria, DNA repair disease, 4-hydroxyphenylacetic aciduria, 5-nucleotidase syndrome, antigen-peptide-transporter 2 deficiency, APO A-i deficiency, cardiomyopathy hypogonadism metabolic anomalies, deficiency of coenzyme q cytochrome c reductase, defective apolipoprotein b-100, sulfide quinone oxidoreductase deficiency, congenital disorder of deglycosylation, hypoalphalipoproteinemia, primary, 2, NAD(P)HX dehydratase deficiency, inborn disorder of aspartate family metabolism, weinstein kliman scully syndrome, glycoprotein metabolism disease, inherited thyroid metabolism disease, tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, combined ApoA-I and ApoC-III deficiency, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 1, Waldenstrom macroglobulinemia, mucopolysaccharidosis or mucopolysaccharidosis-like disorder, disorder of peptide and amine metabolism, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis, Lane Hamilton syndrome, SQSTM1-related multisystem proteinopathy, hypertriglyceridemia 2, autosomal dominant dopa-responsive dystonia

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

4 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 benign, 1 benign; affects, 1 affects

ClinVar	Variant (HGVS)	Gene	Classification	Review
3068178	NM_004213.5(SLC28A1):c.1368del (p.Leu458fs)	SLC28A1	Uncertain significance	criteria provided, single submitter
634889	NM_004213.5(SLC28A1):c.1682G>A (p.Arg561Gln)	SLC28A1	Affects	no assertion criteria provided
634887	NM_004213.5(SLC28A1):c.1636T>C (p.Ser546Pro)	SLC28A1	Benign	criteria provided, single submitter
634888	NM_004213.5(SLC28A1):c.1528C>T (p.Arg510Cys)	SLC28A1	Benign; Affects	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
SLC28A1	HGNC:11001	ENSG00000156222	O00337	Sodium/nucleoside cotransporter 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC28A1	Sodium/nucleoside cotransporter 1	Sodium and pyrimidine nucleoside symporter of the plasma membrane that imports uridine, thymidine and cytidine into cells by coupling their transport to the transmembrane sodium electrochemical gradient.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC28A1	Other/Unknown	no		CNT_N_dom, C_nuclsd_transpt, Gate_dom

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
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC28A1	90	tissue_specific	marker	right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC28A1	722

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC28A1	O00337	81.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	951.7×	0.004	SLC28A1
Transport of vitamins, nucleosides, and related molecules	1	271.9×	0.007	SLC28A1
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC28A1
Transport of small molecules	1	25.1×	0.040	SLC28A1

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
nucleoside import across plasma membrane	1	16852.0×	3e-04	SLC28A1
pyrimidine nucleobase transport	1	8426.0×	3e-04	SLC28A1
azole transmembrane transport	1	8426.0×	3e-04	SLC28A1
cytidine transport	1	4213.0×	4e-04	SLC28A1
pyrimidine-containing compound transmembrane transport	1	3370.4×	4e-04	SLC28A1
uridine transmembrane transport	1	2808.7×	4e-04	SLC28A1
nucleoside transmembrane transport	1	2808.7×	4e-04	SLC28A1
purine nucleobase transmembrane transport	1	2808.7×	4e-04	SLC28A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
SLC28A1	ADENOSINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC28A1	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ADENOSINE	4	SLC28A1
URIDINE	3	SLC28A1
TECADENOSON	2	SLC28A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC28A1	7	Binding:5, ADMET: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

3 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)
ADENOSINE	4	SLC28A1
URIDINE	3	SLC28A1
TECADENOSON	2	SLC28A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC28A1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.