UROC1

Chr 3

urocanate hydratase 1

Also known as: HMFN0320, UROCD

NCBI Gene: 131669 ENSG00000159650 UniProt: Q96N76

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtUrocanase deficiency

Clinical highlights

Gene–disease validity (ClinGen)

Limited · urocanic aciduria · AR · ClinGen 2026

not for standalone diagnostic reporting

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in UROC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,031 rare PASS variants

Rare truncating (LoF)

1 in 630

185 rare PASS variants

Rare synonymous (reference)

1 in 67

431 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UROC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 55	1 in 980
South Asian	~43k	1 in 32	1 in 630
Remaining (unassigned)	~30k	1 in 33	1 in 450
European (Finnish)	~27k	1 in 150	1 in 3,400
Admixed American	~22k	1 in 37	1 in 370
African / African American	~21k	1 in 38	1 in 390
East Asian	~20k	1 in 35	1 in 520
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 38	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 20 coding exons well covered in gnomAD exomes and genomes.? see exons ↓