UPB1

beta-ureidopropionase 1

Basic information

Region (hg38): 22:24494107-24528390

Links

ENSG00000100024 ∙ NCBI:51733 ∙ OMIM:606673 ∙ HGNC:16297 ∙ Uniprot:Q9UBR1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• beta-ureidopropionase deficiency (Strong), mode of inheritance: AR
• beta-ureidopropionase deficiency (Supportive), mode of inheritance: AR
• beta-ureidopropionase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Beta-ureidopropionase 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	15385443; 17964839; 22525402; 35151535
As with many disorders involving seizure risk, optimal control is beneficial; Normal neurologic development has been described (in addition to severe neurologic manifestations)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UPB1 gene.

• not provided (5 variants)
• Deficiency of beta-ureidopropionase (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UPB1 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			4	26	5	35
missense		2	62	3		67
nonsense	4	1	1			6
start loss						0
frameshift	4	2	1			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region			8	5		13
non coding			14	15	5	34
Total	8	8	83	44	10

Highest pathogenic variant AF is 0.0000263

Variants in UPB1

This is a list of pathogenic ClinVar variants found in the UPB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-24495324-C-G		Deficiency of beta-ureidopropionase	Benign (Jan 13, 2018)
22-24495325-C-T		Deficiency of beta-ureidopropionase	Uncertain significance (Apr 27, 2017)
22-24495339-T-C		Deficiency of beta-ureidopropionase	Uncertain significance (Jan 13, 2018)
22-24495341-C-T		Deficiency of beta-ureidopropionase	Likely benign (Jan 13, 2018)
22-24495343-C-T		Deficiency of beta-ureidopropionase	Uncertain significance (Jan 13, 2018)
22-24495377-G-C		Deficiency of beta-ureidopropionase	Uncertain significance (Aug 12, 2021)
22-24495387-A-T		Deficiency of beta-ureidopropionase	Benign (Jan 13, 2018)
22-24495393-G-A		Deficiency of beta-ureidopropionase	Uncertain significance (Jan 13, 2018)
22-24495397-C-G		Deficiency of beta-ureidopropionase	Likely benign (Jan 12, 2018)
22-24495408-C-G		Deficiency of beta-ureidopropionase	Uncertain significance (Feb 18, 2020)
22-24495412-C-T			Likely benign (Dec 02, 2021)
22-24495413-G-A			Uncertain significance (Jul 13, 2016)
22-24495428-C-T			Likely benign (Jun 06, 2021)
22-24495429-T-C		Deficiency of beta-ureidopropionase	Uncertain significance (Aug 23, 2022)
22-24495441-T-C		Deficiency of beta-ureidopropionase • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 12, 2021)
22-24495444-A-G		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)
22-24495449-CA-C			Likely pathogenic (Sep 23, 2023)
22-24495450-A-C		Deficiency of beta-ureidopropionase	Likely benign (May 28, 2019)
22-24495457-G-A		Deficiency of beta-ureidopropionase	Conflicting classifications of pathogenicity (Aug 22, 2022)
22-24495462-C-T			Uncertain significance (Aug 14, 2022)
22-24495465-A-T		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
22-24495485-G-A		Deficiency of beta-ureidopropionase	Likely benign (Oct 05, 2023)
22-24495494-G-A		Deficiency of beta-ureidopropionase	Conflicting classifications of pathogenicity (Oct 05, 2023)
22-24495498-AG-A			Pathogenic (Mar 04, 2022)
22-24500046-A-G			not provided (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UPB1	protein_coding	protein_coding	ENST00000326010	10	61153

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.36e-12	0.132	125018	2	728	125748	0.00291

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.866	261	224	1.16	0.0000145	2512
Missense in Polyphen		101	83.604	1.2081		908
Synonymous	-1.42	110	92.6	1.19	0.00000691	739
Loss of Function	0.630	19	22.2	0.856	0.00000134	233

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00441	0.00441
Ashkenazi Jewish	0.00486	0.00487
East Asian	0.000381	0.000381
Finnish	0.00176	0.00176
European (Non-Finnish)	0.00330	0.00329
Middle Eastern	0.000381	0.000381
South Asian	0.00321	0.00321
Other	0.00554	0.00555

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts N-carbamoyl-beta-aminoisobutyrate and N- carbamoyl-beta-alanine (3-ureidopropanoate) to, respectively, beta-aminoisobutyrate and beta-alanine, ammonia and carbon dioxide.
• Disease: DISEASE: Beta-ureidopropionase deficiency (UPB1D) [MIM:613161]: An inborn error of metabolism due to a defect in pyrimidine degradation. It is characterized by muscular hypotonia, dystonic movements, scoliosis, microcephaly and severe developmental delay. Patients show strongly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine. {ECO:0000269|PubMed:15385443}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Pantothenate and CoA biosynthesis - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Fluoropyrimidine Pathway, Pharmacokinetics;Carnosinuria, carnosinemia;Ureidopropionase deficiency;GABA-Transaminase Deficiency;Pyrimidine Metabolism;Beta-Alanine Metabolism;UMP Synthase Deiciency (Orotic Aciduria);MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Fluoropyrimidine Activity;pyrimidine ribonucleosides degradation;Pyrimidine metabolism;Pyrimidine catabolism;Nucleobase catabolism;Metabolism of nucleotides;Alanine Aspartate Asparagine metabolism;Metabolism;uracil degradation;thymine degradation;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.281
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.27

Haploinsufficiency Scores

• pHI: 0.0961
• hipred: Y
• hipred_score: 0.514
• ghis: 0.461

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.867

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Upb1

Gene ontology

• Biological process: beta-alanine metabolic process;beta-alanine biosynthetic process via 3-ureidopropionate;pyrimidine nucleoside catabolic process
• Cellular component: cytosol;extracellular exosome
• Molecular function: beta-ureidopropionase activity;metal ion binding