UROC1

urocanate hydratase 1

Basic information

Region (hg38): 3:126481165-126517773

Links

ENSG00000159650 ∙ NCBI:131669 ∙ OMIM:613012 ∙ HGNC:26444 ∙ Uniprot:Q96N76 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• urocanic aciduria (Definitive), mode of inheritance: AR
• urocanic aciduria (Supportive), mode of inheritance: AR
• urocanic aciduria (Limited), mode of inheritance: AR
• urocanic aciduria (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Urocanase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	5124677; 6107814; 19304569

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UROC1 gene.

• not provided (49 variants)
• Inborn genetic diseases (41 variants)
• Urocanate hydratase deficiency (12 variants)
• not specified (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UROC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				22	6	28
missense			43	9	4	56
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	3	2	6
non coding					3	3
Total	2	0	43	31	13

Variants in UROC1

This is a list of pathogenic ClinVar variants found in the UROC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-126482378-G-A			Likely benign (Sep 01, 2022)
3-126482378-G-T		not specified	Uncertain significance (Sep 12, 2023)
3-126482435-G-A		UROC1-related disorder	Likely benign (Nov 01, 2023)
3-126482448-T-C			Likely benign (Aug 16, 2018)
3-126482476-G-A		not specified	Uncertain significance (Oct 14, 2023)
3-126482478-C-T		not specified	Uncertain significance (Oct 06, 2022)
3-126483373-T-C		not specified	Uncertain significance (Jun 30, 2022)
3-126483413-C-T		not specified	Uncertain significance (Mar 20, 2023)
3-126483414-G-A		not specified • Urocanate hydratase deficiency	Benign (Dec 05, 2021)
3-126483421-G-A		not specified	Uncertain significance (Feb 21, 2024)
3-126483429-G-A			Likely benign (Jul 01, 2022)
3-126483444-G-A		UROC1-related disorder	Likely benign (Sep 26, 2019)
3-126483447-T-C		UROC1-related disorder	Likely benign (Apr 25, 2019)
3-126483452-C-T		not specified	Uncertain significance (Jan 08, 2024)
3-126483476-A-C			Likely benign (Dec 14, 2017)
3-126488205-C-T		not specified	Uncertain significance (Jul 27, 2021)
3-126488206-G-A			Benign/Likely benign (Jun 01, 2021)
3-126488215-G-A		UROC1-related disorder	Likely benign (Mar 14, 2019)
3-126488242-G-A			Likely benign (Mar 29, 2018)
3-126488259-C-T		not specified	Uncertain significance (Oct 26, 2021)
3-126488283-C-T			Likely benign (Nov 18, 2017)
3-126488284-G-A		not specified	Uncertain significance (Mar 06, 2015)
3-126489281-C-T		not specified	Uncertain significance (Oct 20, 2021)
3-126489294-C-T		not specified	Uncertain significance (Apr 08, 2022)
3-126489308-G-T		not specified	Uncertain significance (Jun 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UROC1	protein_coding	protein_coding	ENST00000383579	21	36493

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.08e-15	0.566	125444	2	302	125748	0.00121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.509	473	443	1.07	0.0000287	4774
Missense in Polyphen		274	252.57	1.0848		2707
Synonymous	-0.698	194	182	1.07	0.0000127	1462
Loss of Function	1.68	29	40.5	0.715	0.00000186	451

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00215	0.00215
Ashkenazi Jewish	0.00	0.00
East Asian	0.0107	0.0107
Finnish	0.0000476	0.0000462
European (Non-Finnish)	0.000318	0.000316
Middle Eastern	0.0107	0.0107
South Asian	0.000360	0.000359
Other	0.000979	0.000978

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Urocanase deficiency (UROCD) [MIM:276880]: An inborn error of histidine metabolism resulting in urocanic aciduria and neurological manifestations including mental retardation, ataxia, episodic aggressive behavior or exaggerated affection-seeking. {ECO:0000269|PubMed:19304569}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Histidine metabolism - Homo sapiens (human);Histidine Metabolism;Histidinemia;Histidine catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;histidine degradation (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.810
• rvis_EVS: 0.32
• rvis_percentile_EVS: 72.83

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.250
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.887

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Uroc1

Gene ontology

• Biological process: histidine catabolic process;histidine catabolic process to glutamate and formamide;histidine catabolic process to glutamate and formate
• Cellular component: cytosol
• Molecular function: urocanate hydratase activity