Urocanic aciduria

Summary

Urocanic aciduria (MONDO:0010167) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 17
• Phenotypes (HPO): 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0002078	Truncal ataxia	Very frequent (80-99%)
HP:0002136	Broad-based gait	Very frequent (80-99%)
HP:0002345	Action tremor	Very frequent (80-99%)
HP:0002719	Recurrent infections	Very frequent (80-99%)
HP:0006801	Hyperactive deep tendon reflexes	Very frequent (80-99%)
HP:0007979	Gaze-evoked horizontal nystagmus	Very frequent (80-99%)
HP:0010904	Abnormal circulating histidine concentration	Very frequent (80-99%)
HP:0012237	Urocanic aciduria	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	urocanic aciduria
Mondo ID	MONDO:0010167
MeSH	C536479
OMIM	276880
Orphanet	210128
DOID	DOID:0112180
ICD-11	61773927
SNOMED CT	60952007
UMLS	C0268514
MedGen	120644
GARD	0008539
Is cancer (heuristic)	no

Also known as: encephalopathy due to urocanase deficiency · urocanase deficiency · urocanic aciduria · urocanic aciduria (disease) · UROCD

Data availability: 17 ClinVar variants · 4 GenCC gene-disease records · 1 HPO phenotype.

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 histidine metabolism › urocanic aciduria

Related subtypes (1): histidinemia

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

17 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 4 benign, 3 pathogenic, 3 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3776010	NM_144639.3(UROC1):c.903-29del	UROC1	Pathogenic	criteria provided, single submitter
407	NM_144639.3(UROC1):c.1348C>T (p.Arg450Cys)	UROC1	Pathogenic	no assertion criteria provided
973479	NM_144639.3(UROC1):c.1448_1449del (p.Ser483fs)	UROC1	Pathogenic	criteria provided, single submitter
973482	NM_144639.3(UROC1):c.855G>A (p.Trp285Ter)	UROC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
638417	NM_144639.3(UROC1):c.854G>A (p.Trp285Ter)	UROC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032449	NM_144639.3(UROC1):c.640G>A (p.Gly214Ser)	UROC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
212549	NM_144639.3(UROC1):c.40C>T (p.Arg14Trp)	UROC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3186999	NM_144639.3(UROC1):c.615G>C (p.Met205Ile)	UROC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
408	NM_144639.3(UROC1):c.209T>C (p.Leu70Pro)	UROC1	Uncertain significance	criteria provided, single submitter
1684193	NM_144639.3(UROC1):c.1609-31T>G	LOC126806801	Benign	criteria provided, multiple submitters, no conflicts
130699	NM_144639.3(UROC1):c.1845C>T (p.Ala615=)	UROC1	Benign	criteria provided, multiple submitters, no conflicts
1684194	NM_144639.3(UROC1):c.1146-33A>G	UROC1	Benign	criteria provided, multiple submitters, no conflicts
1684195	NM_144639.3(UROC1):c.351+18C>T	UROC1	Benign	criteria provided, multiple submitters, no conflicts
784023	NM_144639.3(UROC1):c.132G>A (p.Ala44=)	UROC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
789169	NM_144639.3(UROC1):c.562C>T (p.Arg188Trp)	UROC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
791089	NM_144639.3(UROC1):c.59G>A (p.Arg20Gln)	UROC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
973468	NM_144639.3(UROC1):c.903-29G>A	UROC1	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
UROC1	Moderate	Autosomal recessive	urocanic aciduria	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UROC1	Orphanet:210128	Urocanic aciduria

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
UROC1	HGNC:26444	ENSG00000159650	Q96N76	Urocanate hydratase	gencc,clinvar

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)
UROC1	Other/Unknown	no		Urocanase_CS, Urocanase-like, Urocanase_Rossmann-like

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
UROC1	41	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UROC1	840

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UROC1	Q96N76	95.68

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
Histidine catabolism	1	1142.0×	9e-04	UROC1

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
obsolete L-histidine catabolic process to glutamate and formamide	1	4213.0×	4e-04	UROC1
obsolete L-histidine catabolic process to glutamate and formate	1	4213.0×	4e-04	UROC1
L-histidine catabolic process	1	2407.4×	4e-04	UROC1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UROC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	UROC1

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)
UROC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.