UMPS

uridine monophosphate synthetase, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 3:124730432-124749273

Links

ENSG00000114491 ∙ NCBI:7372 ∙ OMIM:613891 ∙ HGNC:12563 ∙ Uniprot:P11172 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orotic aciduria (Definitive), mode of inheritance: AR
• orotic aciduria (Strong), mode of inheritance: AR
• orotic aciduria (Supportive), mode of inheritance: AR
• orotic aciduria (Moderate), mode of inheritance: AR
• orotic aciduria (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Orotic aciduria	AR	Biochemical	Pyrimidine replacement therapy, along with urinary orotic acid monitoring, can be beneficial	Allergy/Immunology/Infectious; Biochemical; Hematologic; Neurologic	13651334; 14110033; 5347440; 6828110; 6717503; 9042911; 19562503

ClinVar

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

• Orotic aciduria (185 variants)
• Hereditary orotic aciduria, type 1 (56 variants)
• not provided (27 variants)
• Inborn genetic diseases (16 variants)
• not specified (4 variants)
• UMPS-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UMPS 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			3	20	4	27
missense		1	38	1	2	42
nonsense	2		2			4
start loss						0
frameshift		1	3			4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding			97	18	45	160
Total	2	2	143	39	51

Highest pathogenic variant AF is 0.0000132

Variants in UMPS

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

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

Position	Type	Phenotype	Significance	ClinVar
3-124730444-A-G		Orotic aciduria	Benign (Dec 05, 2021)
3-124730453-A-G		Orotic aciduria	Uncertain significance (Jan 13, 2018)
3-124730473-T-A			Uncertain significance (Mar 01, 2024)
3-124730473-T-C			Uncertain significance (Sep 16, 2018)
3-124730481-G-C		Hereditary orotic aciduria, type 1	Uncertain significance (Apr 01, 2024)
3-124730489-A-G		Orotic aciduria • Hereditary orotic aciduria, type 1	Benign/Likely benign (Sep 26, 2023)
3-124730492-T-C		Orotic aciduria • Hereditary orotic aciduria, type 1	Benign/Likely benign (Jan 18, 2024)
3-124730501-A-G		Hereditary orotic aciduria, type 1	Likely benign (Apr 16, 2021)
3-124730516-G-A		Hereditary orotic aciduria, type 1	Likely benign (Jul 06, 2022)
3-124730527-A-T		Hereditary orotic aciduria, type 1	Uncertain significance (Nov 14, 2020)
3-124730559-A-G		not specified • Orotic aciduria • Hereditary orotic aciduria, type 1	Conflicting classifications of pathogenicity (Jan 12, 2024)
3-124730576-C-T		Orotic aciduria	Uncertain significance (Feb 09, 2018)
3-124730597-C-A		Hereditary orotic aciduria, type 1 • UMPS-related disorder	Conflicting classifications of pathogenicity (Dec 31, 2019)
3-124735073-A-T		Hereditary orotic aciduria, type 1	Likely benign (Apr 01, 2022)
3-124735089-A-G		Hereditary orotic aciduria, type 1	Likely benign (Jun 01, 2021)
3-124735110-C-T		UMPS-related disorder	Likely benign (Aug 17, 2019)
3-124735120-CA-C		Cardiomyopathy • Orotic aciduria	Pathogenic (Mar 06, 2024)
3-124735146-C-T			Likely benign (Mar 30, 2018)
3-124735158-G-A		Hereditary orotic aciduria, type 1	Likely benign (Jun 05, 2022)
3-124735166-C-A		Hereditary orotic aciduria, type 1	Uncertain significance (Aug 14, 2020)
3-124735190-T-C		Hereditary orotic aciduria, type 1	Uncertain significance (Aug 24, 2021)
3-124735222-A-G			Likely benign (Sep 16, 2018)
3-124735235-CA-C		Hereditary orotic aciduria, type 1	Uncertain significance (Jun 30, 2018)
3-124735254-A-G		Hereditary orotic aciduria, type 1	Likely benign (Aug 02, 2021)
3-124735327-A-G			Benign (Jun 19, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UMPS	protein_coding	protein_coding	ENST00000232607	6	14828

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000105	0.950	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	216	268	0.805	0.0000141	3107
Missense in Polyphen		53	80.839	0.65562		933
Synonymous	0.256	99	102	0.968	0.00000550	999
Loss of Function	1.78	9	16.9	0.533	9.01e-7	212

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000316	0.000308
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Fluoropyrimidine Pathway, Pharmacokinetics;Fluoropyrimidine Activity;Pyrimidine metabolism;Metabolism of nucleotides;Pyrimidine biosynthesis;Metabolism;Pentose phosphate cycle;Nucleobase biosynthesis;UMP biosynthesis;superpathway of pyrimidine ribonucleotides <i>de novo</i> biosynthesis;Pyrimidine nucleotides nucleosides metabolism;superpathway of pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.272

Intolerance Scores

• loftool: 0.579
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.147
• hipred: N
• hipred_score: 0.346
• ghis: 0.637

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.712

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Umps

Gene ontology

• Biological process: 'de novo' pyrimidine nucleobase biosynthetic process;UMP biosynthetic process;female pregnancy;lactation;cellular response to drug;'de novo' UMP biosynthetic process;pyrimidine nucleoside biosynthetic process
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: orotate phosphoribosyltransferase activity;orotidine-5'-phosphate decarboxylase activity