5-fluorouracil toxicity

Summary

5-fluorouracil toxicity (MONDO:0027652) is a disease with 1 cohort gene and 3 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 3
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	5-fluorouracil toxicity
Mondo ID	MONDO:0027652
Orphanet	240839
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › poisoning › chemotherapy-induced toxicity › 5-fluorouracil toxicity

Related subtypes (4): 5-fluorouracil poisoning, cisplatin toxicity, irinotecan toxicity, methotrexate toxicity

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 drug response, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
433	NM_000110.4(DPYD):c.2921A>T (p.Asp974Val)	DPYD	Pathogenic	no assertion criteria provided
432	NM_000110.4(DPYD):c.1905+1G>A	DPYD	drug response	reviewed by expert panel
88974	NM_000110.4(DPYD):c.2846A>T (p.Asp949Val)	DPYD	drug response	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DPYD	Orphanet:1675	Dihydropyrimidine dehydrogenase deficiency
DPYD	Orphanet:293948	1p21.3 microdeletion syndrome

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
DPYD	HGNC:3012	ENSG00000188641	Q12882	Dihydropyrimidine dehydrogenase [NADP(+)]	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPYD	Dihydropyrimidine dehydrogenase [NADP(+)]	Involved in pyrimidine base degradation.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DPYD	Enzyme (other)	yes	1.3.1.2	Dihydroorotate_DH_cat, Helical_ferredxn, Aldolase_TIM

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
germinal epithelium of ovary	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPYD	274	ubiquitous	marker	germinal epithelium of ovary, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DPYD	2,591

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DPYD	Q12882	96.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Pyrimidine catabolism	1	878.5×	0.001	DPYD

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
purine nucleobase catabolic process	1	16852.0×	2e-04	DPYD
thymidine catabolic process	1	16852.0×	2e-04	DPYD
beta-alanine biosynthetic process	1	16852.0×	2e-04	DPYD
TMP catabolic process	1	16852.0×	2e-04	DPYD
pyrimidine nucleobase catabolic process	1	8426.0×	2e-04	DPYD
uracil catabolic process	1	8426.0×	2e-04	DPYD
thymine catabolic process	1	5617.3×	3e-04	DPYD
CMP catabolic process	1	2106.5×	6e-04	DPYD
UMP catabolic process	1	2106.5×	6e-04	DPYD
dCMP catabolic process	1	1872.4×	6e-04	DPYD
dUMP catabolic process	1	1872.4×	6e-04	DPYD
xenobiotic catabolic process	1	561.7×	0.002	DPYD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DPYD	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENILURACIL	3	DPYD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DPYD	3	Functional:2, Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DPYD	1.3.1.2	dihydropyrimidine dehydrogenase (NADP+)

Pharmacogenomics

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

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
DPYD	1

Chemical tractability of cohort targets

1 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)
ENILURACIL	3	DPYD

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	1	DPYD
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: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06258525	PHASE2	NOT_YET_RECRUITING	SAMe in Prevention of Oxaliplatin-associated Liver Injury
NCT03486340	Not specified	COMPLETED	Prevention of Chest Pain in Chemo-treated Cancer Patients
NCT04042298	Not specified	COMPLETED	Microvascular Function in Patients Undergoing 5-Fluorouracil Chemotherapy