UROC1

Chr 3AR

urocanate hydratase 1

Also known as: HMFN0320, UROCD

NCBI Gene: 131669 ENSG00000159650 UniProt: Q96N76 OMIM: 613012

The protein encoded by this gene is urocanase, an enzyme that catalyzes the second step of histidine catabolism by converting urocanic acid to formiminoglutamic acid. Mutations cause urocanase deficiency, which presents with urocanic aciduria and intellectual disability. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM

This gene encodes an enzyme involved in the second step of histidine catabolism, metabolizing urocanic acid to formiminoglutamic acid. Deficiency of this enzyme results in urocanic aciduria, and is an apparent cause of mental retardation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2021]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.971 OMIM phenotype

Clinical Summary— UROC1

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Gene-Disease Validity (ClinGen)

urocanic aciduria · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 140 VUS of 224 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.68

OE 0.72 (0.53–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.51Z-score

OE missense 1.07 (0.99–1.15)

473 obs / 442.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.72 (0.53–0.97)

0≤0.351.4

Missense OE?1.07 (0.99–1.15)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 29 / 40.5Missense obs/exp: 473 / 442.8Syn Z: -0.70

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedUROC1-related urocanase deficiencyOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6745th %ile

GOF

0.5366th %ile

LOF

0.3355th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

224 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic2

VUS140

Likely Benign50

Benign13

Conflicting4

Pathogenic

Likely Pathogenic

140

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	0	3
Likely Pathogenic	2	0	0	0	2
VUS	0	139	1	0	140
Likely Benign	0	13	4	33	50
Benign	0	3	5	5	13
Conflicting	—				4
Total	4	156	10	38	212

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap UROC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →