1. Panels
  2. Intellectual disability
  3. UROC1
Genes in panel
Prev Next
Regions in panel
Prev Next

Intellectual disability

Gene: UROC1

Green List (high evidence)
UROC1 (urocanate hydratase 1)
EnsemblGeneIds (GRCh38): ENSG00000159650
EnsemblGeneIds (GRCh37): ENSG00000159650
OMIM: 613012, Gene2Phenotype
UROC1 is in 6 panels

5 reviews

Ida Ertmanska (Genomics England Curator)

Red List (low evidence)

Comment on list classification: There are 5 individuals from 4 families reported in literature with biallelic variants in UROC1 and urocanic aciduria. 2/5 individuals with Urocanase deficiency were asymptomatic, 2/5 presented with intellectual disability (1 mild, 1 not specified), and 1 individual was noted to have a non-specific 'neurologic' phenotype. In addition, PMID: 30619714 and PMID: 32439973 state that the biochemical phenotype of Urocanase deficiency is benign. In 2/4 studies, only UROC1 targeted sequencing was performed. As there is conflicting evidence for this gene-disease association, UROC1 should be downgraded to Red for Intellectual disability.
Created: 13 Nov 2025, 6:12 p.m. | Last Modified: 13 Nov 2025, 6:18 p.m.
Panel Version: 9.180
PMID: 19304569 Espinos et al., 2009
Female proband, compound het for NM_144639.3(UROC1):c.1348C>T (p.Arg450Cys) & NM_144639.3(UROC1):c.209T>C (p.Leu70Pro). Sequenced UROC1 gene only. Phenotype: ataxia, ataxic gait, action tremor, dysarthric speech, slight nystagmus. Cognitive evaluation rated her IQ at 54 - mild ID (Wechsler Intelligence Scale for ChildrenRevised: verbal 57 and manipulation 60).
Disease association disputed in PMID: 30619714.

PMID: 27391121 Al-Shamsi et al., 2016
Proband homozygous for NM_144639.3(UROC1):c.855G>A (p.Trp285Ter) - rare in gnomAD v4.1.0, 10 alleles, no homozygotes. Patient phenotype: Intellectual disabilities, attention deficit and hyperactivity disorder, hyperextensible joints, elevated imidazole propionate. Seq method: WES.

PMID: 30619714 Glinton et al., 2018
Case 1 - 27yo female - urocanic aciduria detected at 8 weeks of age; developed normally, psychological assessment at 3yo using the McCarthy Scales of Children's Abilities gave a general cognitive score of 115 (83rd percentile for age).
Case 2 - 21yo male, asymptomatic brother of Case1 with urocanic aciduria (detected on biochemical testing).
Both siblings compound het for NM_144639.3(UROC1):c.356C>G (p.Pro119Arg) and NM_144639.3(UROC1):c.907G>C (p.Ala303Pro) - parents confirmed as carriers. Seq method: UROC1 only.

PMID: 32439973 Alaimo et al., 2020
Patient 75 - phenotype: "Neurologic (with or without other organ systems)"; 5yo male homozygous for NM_144639.3(UROC1):c.855G>A (p.Trp285Ter) with urocanic aciduria. Seq method: exome seq. Authors note that 'the biochemical phenotype is benign and not causative of the patient phenotype'.
Patient 65 - Phenotype: "Neurologic (with or without other organ systems)" - 7months old female - normal metabolomic findings; homozygous for c.1054G>A, p.Ala352Thr in UROC1 - MAF 0.001684 in gnomAD v4.1.0 - Likely Benign.

This gene is putatively associated with Urocanase deficiency , OMIM:276880 (OMIM accessed 13th Nov 2025). Gene is currently rated Red for Intellectual disability in PanelApp Australia.
Created: 13 Nov 2025, 5:55 p.m. | Last Modified: 13 Nov 2025, 6:17 p.m.
Panel Version: 9.180

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Urocanase deficiency , OMIM:276880; urocanic aciduria, MONDO:0010167

Publications

Created: 13 Nov 2025, 5:55 p.m.
Last Modified: 13 Nov 2025, 6:18 p.m.
Panel version: 9.180

Caroline Wright (Sanger)

I don't know

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
UROCANASE DEFICIENCY (UROD)

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Uncertain
Created: 27 Jul 2017, 8:51 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; GEL_ID_green_20160217; neuro_20160418_strict; Uncertain. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:40 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 2 Aug 2017, 11:24 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

I don't know

Created: 23 Feb 2016, 10:14 a.m.

Panel version: 0.306

Richard Scott (Genomics England Curator)

Comment on list classification: Confirmed DD gene
Created: 8 Feb 2016, 2:11 a.m.
Created: 8 Feb 2016, 2:11 a.m.

Panel version: 0.292

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
Phenotypes
  • ?Urocanase deficiency , OMIM:276880
  • urocanic aciduria, MONDO:0010167
Tags
Q4_25_demote_red
OMIM
613012
Clinvar variants
Variants in UROC1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

13 Nov 2025, Gel status: 3

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: UROC1 were changed from UROCANASE DEFICIENCY (UROD) to ?Urocanase deficiency , OMIM:276880; urocanic aciduria, MONDO:0010167

13 Nov 2025, Gel status: 3

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: UROC1 were set to 19304569

13 Nov 2025, Gel status: 3

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q4_25_demote_red tag was added to gene: UROC1.

29 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to UROC1.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

8 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

8 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

UROC1 was added to Intellectual disabilitypanel. Sources: Expert Review Amber

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

UROC1 was created by ellenmcdonagh