UROS

uroporphyrinogen III synthase

Basic information

Region (hg38): 10:125784980-125823288

Links

ENSG00000188690 ∙ NCBI:7390 ∙ OMIM:606938 ∙ HGNC:12592 ∙ Uniprot:P10746 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cutaneous porphyria (Definitive), mode of inheritance: AR
• cutaneous porphyria (Strong), mode of inheritance: AR
• cutaneous porphyria (Strong), mode of inheritance: AR
• cutaneous porphyria (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Porphyria, congenital erythropoietic	AR	Dermatologic; Hematologic	Transfusions can be beneficial; Individuals can prevent with bleeding diatheses, and prompt treatment may be beneficial; Limitation to sun exposure may be beneficial due ot photosensitivity; Manifestations such as thrombocytopenia and hemolytic anemia, may be effectively treated by splenectomy; Use of oral sorbents have been described; BMT has been described in severe cases	Dermatologic; Hematologic	7205063; 3960070; 3100953; 2331520; 2207013; 8829650; 9834209; 12060112; 15703981; 22090724; 22350154; 22816431; 23557135; 23626549

ClinVar

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

• not provided (12 variants)
• Cutaneous porphyria (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UROS 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				12	2	14
missense	7	1	23	6	1	38
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel	1					1
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	8		9
non coding	2		9	10	22	43
Total	13	2	32	28	25

Highest pathogenic variant AF is 0.000243

Variants in UROS

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

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

Position	Type	Phenotype	Significance	ClinVar
10-125788690-C-T		Cutaneous porphyria	Uncertain significance (Jan 12, 2018)
10-125788769-T-C		Cutaneous porphyria	Uncertain significance (Jan 13, 2018)
10-125788772-C-T		Cutaneous porphyria	Likely benign (Jan 13, 2018)
10-125788776-A-C		Cutaneous porphyria	Uncertain significance (Jan 13, 2018)
10-125788812-A-G		Cutaneous porphyria	Uncertain significance (Jan 13, 2018)
10-125788831-C-A		Cutaneous porphyria	Benign (Jan 12, 2018)
10-125788844-T-C		Cutaneous porphyria	Uncertain significance (Jan 13, 2018)
10-125788881-T-C		Inborn genetic diseases	Uncertain significance (Apr 17, 2024)
10-125788915-G-C		UROS-related disorder	Likely benign (Dec 28, 2023)
10-125788916-GGCTTGTGGCGTGGGGCTCTCTGCAGTGCAGCTTACAGGAAGGCCCTGGGCGGCCAGC-G			Pathogenic (Jul 17, 2023)
10-125788923-G-T		Cutaneous porphyria	Pathogenic (Jan 01, 1996)
10-125788926-G-A		Cutaneous porphyria	Likely benign (Jun 06, 2021)
10-125788928-G-A			Benign (Jan 25, 2024)
10-125788956-A-G			Pathogenic (Oct 27, 2021)
10-125788966-C-T			Likely benign (Apr 09, 2023)
10-125788968-GCCAGC-G			Pathogenic (Aug 24, 2021)
10-125788973-C-T			Likely benign (Oct 08, 2022)
10-125788974-G-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
10-125788975-C-T		Cutaneous porphyria	Uncertain significance (Jan 12, 2018)
10-125788982-C-T			Likely benign (Jul 27, 2023)
10-125788983-G-A		Cutaneous porphyria • UROS-related disorder	Conflicting classifications of pathogenicity (Sep 07, 2022)
10-125788988-G-A			Likely benign (Oct 05, 2023)
10-125788993-C-T		Cutaneous porphyria	Pathogenic (Dec 02, 2023)
10-125789003-A-G		UROS-related disorder	Benign (Jun 26, 2023)
10-125789008-A-G		UROS-related disorder	Likely benign (Mar 22, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UROS	protein_coding	protein_coding	ENST00000368797	9	34672

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0316	0.960	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0817	142	139	1.02	0.00000715	1707
Missense in Polyphen		49	56.651	0.86494		644
Synonymous	0.320	55	58.1	0.947	0.00000356	515
Loss of Function	2.31	5	14.5	0.345	6.15e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000308	0.000308
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins. Porphyrins act as cofactors for a multitude of enzymes that perform a variety of processes within the cell such as methionine synthesis (vitamin B12) or oxygen transport (heme).
• Disease: DISEASE: Note=Severe congenital erythropoietic porphyria is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non- immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.
• Pathway: Porphyrin and chlorophyll metabolism - Homo sapiens (human);Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Porphyrin Metabolism;Heme Biosynthesis;hemoglobins chaperone;Heme biosynthesis;Metabolism of porphyrins;Metabolism;Porphyrin metabolism;tetrapyrrole biosynthesis;heme biosynthesis (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.173
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.49

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.394
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uros
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: uroporphyrinogen III biosynthetic process;protoporphyrinogen IX biosynthetic process;heme biosynthetic process
• Cellular component: mitochondrion;cytosol
• Molecular function: uroporphyrinogen-III synthase activity