UPB1

Summary

UPB1 (beta-ureidopropionase 1, HGNC:16297) is a protein-coding gene on chromosome 22q11.23, encoding Beta-ureidopropionase (Q9UBR1). Catalyzes a late step in pyrimidine degradation.

This gene encodes a protein that belongs to the CN hydrolase family. Beta-ureidopropionase catalyzes the last step in the pyrimidine degradation pathway. The pyrimidine bases uracil and thymine are degraded via the consecutive action of dihydropyrimidine dehydrogenase (DHPDH), dihydropyrimidinase (DHP) and beta-ureidopropionase (UP) to beta-alanine and beta-aminoisobutyric acid, respectively. UP deficiencies are associated with N-carbamyl-beta-amino aciduria and may lead to abnormalities in neurological activity.

Source: NCBI Gene 51733 — RefSeq curated summary.

At a glance

• Gene–disease (curated): beta-ureidopropionase deficiency (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 240 total — 13 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_016327

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16297
Approved symbol	UPB1
Name	beta-ureidopropionase 1
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	BUP1
Ensembl gene	ENSG00000100024
Ensembl biotype	protein_coding
OMIM	606673
Entrez	51733

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000326010, ENST00000382760, ENST00000415388, ENST00000486043, ENST00000498140, ENST00000858203, ENST00000858208, ENST00000858209, ENST00000858210, ENST00000858211, ENST00000858212, ENST00000858213, ENST00000858215, ENST00000858217, ENST00000858218, ENST00000858219, ENST00000858220, ENST00000858222, ENST00000858223, ENST00000858224, ENST00000858225, ENST00000858226

RefSeq mRNA: 1 — MANE Select: NM_016327 NM_016327

CCDS: CCDS13827

Canonical transcript exons

ENST00000326010 — 10 exons

Exon	Start	End
ENSE00000651713	24500107	24500278
ENSE00001904746	24525711	24528390
ENSE00001921738	24495332	24495507
ENSE00003571220	24502126	24502213
ENSE00003602725	24521986	24522028
ENSE00003608623	24510749	24510843
ENSE00003611632	24523619	24523773
ENSE00003646229	24515201	24515370
ENSE00003662831	24513324	24513485
ENSE00003684201	24520387	24520468

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 97.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7215 / max 284.4917, expressed in 23 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191404	0.5024	20
191405	0.1490	16
191406	0.0701	11

Top tissues by expression

267 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.89	gold quality
liver	UBERON:0002107	95.73	gold quality
nephron tubule	UBERON:0001231	91.58	gold quality
kidney epithelium	UBERON:0004819	90.89	gold quality
adult mammalian kidney	UBERON:0000082	88.16	gold quality
renal glomerulus	UBERON:0000074	88.15	gold quality
metanephric glomerulus	UBERON:0004736	88.11	gold quality
kidney	UBERON:0002113	85.09	gold quality
oocyte	CL:0000023	83.82	gold quality
cortex of kidney	UBERON:0001225	82.72	gold quality
jejunal mucosa	UBERON:0000399	82.52	gold quality
buccal mucosa cell	CL:0002336	82.04	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.51	gold quality
metanephros	UBERON:0000081	81.51	gold quality
renal medulla	UBERON:0000362	81.29	gold quality
cerebellar vermis	UBERON:0004720	81.18	silver quality
secondary oocyte	CL:0000655	80.82	gold quality
adult organism	UBERON:0007023	80.49	gold quality
sperm	CL:0000019	80.37	silver quality
vena cava	UBERON:0004087	79.91	gold quality
male germ cell	CL:0000015	79.63	silver quality
jejunum	UBERON:0002115	78.63	gold quality
metanephros cortex	UBERON:0010533	78.50	gold quality
biceps brachii	UBERON:0001507	77.46	gold quality
lateral nuclear group of thalamus	UBERON:0002736	76.81	silver quality
nipple	UBERON:0002030	76.32	gold quality
lateral globus pallidus	UBERON:0002476	75.98	silver quality
upper arm skin	UBERON:0004263	75.07	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting UPB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-8086	97.21	64.13	331
HSA-MIR-3690	96.44	65.18	737

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• An altered homeostasis of beta-aminoisobutyric acid and/or increased oxidative stress might contribute to some of the clinical abnormalities encountered in patients with a beta-ureidopropionase deficiency. (PMID:15385443)
• analysis of the beta-ureidopropionase gene (UPB1) of the first 4 patients presenting with a complete enzyme deficiency, revealed the presence of 2 splice-site mutations (IVS1-2A>G and IVS8-1G>A) and one missense mutation (A85E) (PMID:17065070)
• biochemical and molecular findings of 11 newly identified ss-ureidopropionase deficient patients as well as the analysis of the mutations in a three-dimensional framework were reported. (PMID:22525402)
• analysis of UPB1 variants on 5-FU-related toxicity in the population of all analyzed patients revealed an association between the c.-80C>G (rs2070474) variant and gastrointestinal toxicity (PMID:23238479)
• This study reports the clinical, biochemical, and molecular analysis of a newly identified patient with beta-ureidopropionase deficiency and the effect of the first synonymous mutation in UBP1 affecting pre-mRNA splicing, using the minigene approach. (PMID:24328561)
• High prevalence of p.R326Q in the normal Japanese population indicates that betaUP deficiency is not as rare as generally considered (PMID:24526388)
• The c.977G>A (p.R326Q) is the most common mutation of the UPB1 gene in Chinese. The predicted incidence indicates that beta-ureidopropionase deficiency is significantly underdiagnosed in the Chinese population. (PMID:25236466)
• Crystal structure and pH-dependent allosteric regulation of human beta-ureidopropionase, an enzyme involved in anticancer drug metabolism. (PMID:29976570)
• The compound heterozygous mutations of the UPB1 gene probably underlie the beta-ureidopropinoase deficiency in this fabily pedigree. (PMID:30512155)
• beta-Ureidopropionase deficiency due to novel and rare UPB1 mutations affecting pre-mRNA splicing and protein structural integrity and catalytic activity. (PMID:35151535)
• The relationship between beta-ureidopropionase deficiency due to UPB1 variants and human phenotypes is uncertain. (PMID:35926322)
• Low UPB1 Level Correlates With Poor Prognosis in Lung Adenocarcinoma. (PMID:37859333)
• The Allosteric Regulation of Beta-Ureidopropionase Depends on Fine-Tuned Stability of Active-Site Loops and Subunit Interfaces. (PMID:38136634)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	upb1	ENSDARG00000011521
mus_musculus	Upb1	ENSMUSG00000033427
rattus_norvegicus	Upb1	ENSRNOG00000038258
drosophila_melanogaster	pyd3	FBGN0037513
caenorhabditis_elegans		WBGENE00017440

Paralogs (2): NIT2 (ENSG00000114021), NIT1 (ENSG00000158793)

Protein

Protein identifiers

Beta-ureidopropionase — Q9UBR1 (reviewed: Q9UBR1)

Alternative names: BUP-1, Beta-alanine synthase, N-carbamoyl-beta-alanine amidohydrolase

All UniProt accessions (3): Q9UBR1, F8WC94, Q6AHZ8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes a late step in pyrimidine degradation. Converts N-carbamoyl-beta-alanine (3-ureidopropanoate) into beta-alanine, ammonia and carbon dioxide. Likewise, converts N-carbamoyl-beta-aminoisobutyrate (3-ureidoisobutyrate) into beta-aminoisobutyrate, ammonia and carbon dioxide.

Subunit / interactions. Homodimer, homotetramer, homooctamer; can also form higher homooligomers.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in liver (at protein level).

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Strongly inhibited by 50 mM Zn(2+). Not inhibited by EDTA. Competitively inhibited by beta-alanine, 5-aminolevulinic acid (ALA), beta-aminoisobutyrate and 4-ureidobutyrate.

Pathway. Amino-acid biosynthesis; beta-alanine biosynthesis.

Similarity. Belongs to the carbon-nitrogen hydrolase superfamily. BUP family.

RefSeq proteins (1): NP_057411* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003010	C-N_Hydrolase	Domain
IPR036526	C-N_Hydrolase_sf	Homologous_superfamily
IPR050345	Aliph_Amidase/BUP	Family

Pfam: PF00795

Enzyme classification (BRENDA):

• EC 3.5.1.6 — beta-ureidopropionase (BRENDA: 28 organisms, 71 substrates, 76 inhibitors, 64 Km, 37 kcat entries)

Substrate kinetics (BRENDA)

40 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-CARBAMOYL-BETA-ALANINE	0.0065–60	16
BETA-UREIDOPROPIONIC ACID	0.038–3.74	5
2-METHYL-N-CARBAMOYL-BETA-ALANINE	0.006	2
3-UREIDOPROPANOATE	0.019–0.048	2
3-UREIDOPROPIONIC ACID	0.147–2.14	2
N-CARBAMOYL-BETA-AMINOISOBUTYRIC ACID	1–2.81	2
2-AMINO-3-UREIDOPROPIONIC ACID	0.07	1
2-METHYL-3-UREIDOPROPIONIC ACID	6.59	1
2-PHENYL-3-UREIDOPROPIONIC ACID	84.37	1
2-UREIDOETHANE PHOSPHONIC ACID	20.15	1
2-UREIDOETHANESULFONIC ACID	10.58	1
3-METHYL-3-UREIDOPROPIONIC ACID	3.44	1
BETA-UREIDOISOBUTYRIC ACID	0.018	1
DL-BETA-UREIDOBUTYRIC ACID	4.52	1
GAMMA-UREIDO-N-BUTYRATE	11.6	1

Catalyzed reactions (Rhea), 2 shown:

• 3-(carbamoylamino)propanoate + H2O + 2 H(+) = beta-alanine + NH4(+) + CO2 (RHEA:11184)
• 3-(carbamoylamino)-2-methylpropanoate + H2O + 2 H(+) = (R)-3-amino-2-methylpropanoate + NH4(+) + CO2 (RHEA:37339)

UniProt features (53 total): strand 14, helix 12, sequence variant 10, mutagenesis site 7, active site 3, turn 3, chain 1, domain 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6FTQ	X-RAY DIFFRACTION	2.08
8PT4	ELECTRON MICROSCOPY	3.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBR1-F1	97.10	0.98

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 119 (proton acceptor); 196 (proton donor); 233 (nucleophile)

Post-translational modifications (1): 378

Mutagenesis-validated functional residues (7):

Position	Phenotype
130	loss of catalytic activity.
132	loss of catalytic activity. forms dimers, but no higher oligomers.
208	loss of catalytic activity.
208	loss of catalytic activity. forms dimers, but no higher oligomers.
233	loss of catalytic activity.
299	loss of catalytic activity. forms dimers, but no higher oligomers.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-73621	Pyrimidine catabolism
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-8956319	Nucleotide catabolism

MSigDB gene sets: 244 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PROTEIN_HOMOTETRAMERIZATION, REACTOME_PYRIMIDINE_CATABOLISM, GNF2_GSTM1, GNF2_HPN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (13): in utero embryonic development (GO:0001701), liver development (GO:0001889), CMP catabolic process (GO:0006248), dCMP catabolic process (GO:0006249), obsolete beta-alanine biosynthetic process via 3-ureidopropionate (GO:0033396), UMP catabolic process (GO:0046050), dUMP catabolic process (GO:0046079), pyrimidine nucleoside catabolic process (GO:0046135), protein homooligomerization (GO:0051260), protein homotetramerization (GO:0051289), obsolete beta-alanine metabolic process (GO:0019482), beta-alanine biosynthetic process (GO:0019483), small molecule metabolic process (GO:0044281)

GO Molecular Function (4): beta-ureidopropionase activity (GO:0003837), protein homodimerization activity (GO:0042803), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811)

GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nucleotide catabolism	1
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine ribonucleoside monophosphate catabolic process	2
pyrimidine ribonucleotide catabolic process	2
pyrimidine deoxyribonucleoside monophosphate catabolic process	2
pyrimidine deoxyribonucleotide catabolic process	2
cellular anatomical structure	2
chordate embryonic development	1
gland development	1
hepaticobiliary system development	1
CMP metabolic process	1
dCMP metabolic process	1
UMP metabolic process	1
dUMP metabolic process	1
pyrimidine nucleoside metabolic process	1
nucleoside catabolic process	1
pyrimidine-containing compound catabolic process	1
protein complex oligomerization	1
protein homooligomerization	1
protein tetramerization	1
amino acid biosynthetic process	1
non-proteinogenic amino acid biosynthetic process	1
metabolic process	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
identical protein binding	1
protein dimerization activity	1
catalytic activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UPB1	DPYS	Q14117	817
UPB1	DPYD	Q12882	793
UPB1	UPP1	Q16831	636
UPB1	UMPS	P11172	620
UPB1	UPP2	O95045	597
UPB1	UCK1	Q9HA47	562
UPB1	UCK2	Q9BZX2	553
UPB1	ADSL	P30566	496
UPB1	MTR	Q99707	488
UPB1	TYMP	P19971	476
UPB1	UCKL1	Q9NWZ5	469
UPB1	HPD	P32754	468
UPB1	RTN3	O95197	445
UPB1	AGXT2	Q9BYV1	444
UPB1	DHODH	Q02127	432

IntAct

0 interactions, top by confidence:

BioGRID (2): UPB1 (Co-fractionation), UPB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P1DJE3, A0A2H3E4G0, A2R6M7, A2RA31, A5DNJ4, A9QXE0, B6HCY4, B6HVR6, B6Q5I3, B7H6S5, C7YS90, C8V9R7, D4B1Q8, E3RV84, G2XQT1, G7X8S6, G7XTA8, G9N4E3, I1RP53, K2QXC4, P10045, P20960, P32961, P32962, P32963, P32964, P46010, P60327, P82605, P9WEU5, P9WEU6, Q02068, Q03217, Q03248, Q19A54, Q2U4D6, Q44185, Q500U1, Q5RBM6, Q5S260

Diamond homologs: Q03248, Q5RBM6, Q8H183, Q8VC97, Q964D8, Q9UBR1, Q8VYF5, Q3LRV4, Q42966, O59829, P54608, P60327, Q28IE5, Q3HVN1, Q44185, Q5NHL7, Q5R4L6, Q5S260, Q6INI7, Q6IR61, Q93XI4, Q9NQR4, Q9UYV8, Q9XGI9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

240 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	6
Uncertain significance	115
Likely benign	64
Benign	9

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1071875	NM_016327.3(UPB1):c.352C>T (p.Gln118Ter)	Pathogenic
1405005	NM_016327.3(UPB1):c.674del (p.Phe225fs)	Pathogenic
1702976	NM_016327.3(UPB1):c.364+6T>G	Pathogenic
1702980	NM_016327.3(UPB1):c.916+1_916+2dup	Pathogenic
1939581	NM_016327.3(UPB1):c.193C>T (p.Gln65Ter)	Pathogenic
2106961	NM_016327.3(UPB1):c.97del (p.Glu33fs)	Pathogenic
2264247	NM_016327.3(UPB1):c.641del (p.Gly214fs)	Pathogenic
2627297	NM_016327.3(UPB1):c.670C>T (p.Gln224Ter)	Pathogenic
3017661	NM_016327.3(UPB1):c.874G>T (p.Glu292Ter)	Pathogenic
3233897	NM_016327.3(UPB1):c.254del (p.Ala85fs)	Pathogenic
3336289	NC_000022.10:g.(?24891299)(24898182_24906716)del	Pathogenic
3679693	NM_016327.3(UPB1):c.952_964del (p.Tyr318fs)	Pathogenic
4770134	NM_016327.3(UPB1):c.887_890del (p.Asn296fs)	Pathogenic
1067615	NM_016327.3(UPB1):c.364+1G>C	Likely pathogenic
1702978	NM_016327.3(UPB1):c.1034A>T (p.Asn345Ile)	Likely pathogenic
2138423	NM_016327.3(UPB1):c.811G>A (p.Glu271Lys)	Likely pathogenic
2580806	NM_016327.3(UPB1):c.47del (p.His16fs)	Likely pathogenic
3065964	NM_016327.3(UPB1):c.505C>T (p.Arg169Ter)	Likely pathogenic
977433	NM_016327.3(UPB1):c.148_149dup (p.Asp51fs)	Likely pathogenic

SpliceAI

1656 predictions. Top by Δscore:

Variant	Effect	Δscore
22:24495473:G:GT	donor_gain	1.0000
22:24495523:GC:G	donor_gain	1.0000
22:24495524:C:G	donor_gain	1.0000
22:24495529:C:G	donor_gain	1.0000
22:24500198:C:G	donor_gain	1.0000
22:24502204:G:GT	donor_gain	1.0000
22:24502212:GA:G	donor_gain	1.0000
22:24502214:G:GG	donor_gain	1.0000
22:24507403:G:GA	donor_gain	1.0000
22:24510747:A:AG	acceptor_gain	1.0000
22:24510748:G:GG	acceptor_gain	1.0000
22:24510748:GCT:G	acceptor_gain	1.0000
22:24510748:GCTAT:G	acceptor_gain	1.0000
22:24513322:A:AG	acceptor_gain	1.0000
22:24513323:G:GG	acceptor_gain	1.0000
22:24513323:GCT:G	acceptor_gain	1.0000
22:24513449:G:GT	donor_gain	1.0000
22:24513450:A:T	donor_gain	1.0000
22:24513466:GA:G	donor_gain	1.0000
22:24513483:GAG:G	donor_gain	1.0000
22:24513485:GGTGA:G	donor_loss	1.0000
22:24513486:G:C	donor_loss	1.0000
22:24513487:T:A	donor_loss	1.0000
22:24515357:A:G	donor_gain	1.0000
22:24520464:GCACC:G	donor_gain	1.0000
22:24523615:A:AG	acceptor_gain	1.0000
22:24523616:A:G	acceptor_gain	1.0000
22:24523617:A:G	acceptor_gain	1.0000
22:24523618:G:GA	acceptor_gain	1.0000
22:24523618:GC:G	acceptor_gain	1.0000

AlphaMissense

2524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:24513451:A:T	K196I	0.999
22:24513452:A:C	K196N	0.997
22:24513452:A:T	K196N	0.997
22:24523651:A:C	S317R	0.996
22:24523653:C:A	S317R	0.996
22:24523653:C:G	S317R	0.996
22:24513451:A:C	K196T	0.994
22:24502197:T:G	C116W	0.992
22:24520397:T:A	W268R	0.992
22:24520397:T:C	W268R	0.992
22:24502210:T:A	W121R	0.991
22:24502210:T:C	W121R	0.991
22:24515278:C:G	C233W	0.991
22:24520456:T:A	N287K	0.991
22:24520456:T:G	N287K	0.991
22:24515288:C:G	H237D	0.990
22:24522004:T:C	F298L	0.990
22:24522006:T:A	F298L	0.990
22:24522006:T:G	F298L	0.990
22:24513485:G:C	E207D	0.989
22:24513485:G:T	E207D	0.989
22:24510757:T:C	F125L	0.988
22:24510759:T:A	F125L	0.988
22:24510759:T:G	F125L	0.988
22:24515286:G:C	R236P	0.988
22:24515344:C:A	N255K	0.988
22:24515344:C:G	N255K	0.988
22:24520458:G:C	R288P	0.988
22:24502205:A:T	E119V	0.987
22:24513401:T:A	N179K	0.987

dbSNP variants (sampled 300 via entrez): RS1000088018 (22:24523793 G>C), RS1000160030 (22:24511106 T>C), RS1000191957 (22:24508568 A>C), RS1000312810 (22:24518791 T>G), RS1000391053 (22:24508411 T>C), RS1000518549 (22:24513876 C>T), RS1000648509 (22:24519890 C>T), RS1000662421 (22:24502194 C>A,T), RS1000721596 (22:24508232 T>C), RS1000738840 (22:24514432 C>T), RS1000792675 (22:24496249 T>C), RS1000826352 (22:24513600 G>A,C,T), RS1001004546 (22:24528833 A>T), RS1001223901 (22:24525395 T>C), RS1001453608 (22:24504719 C>T)

Disease associations

OMIM: gene MIM:606673 | disease phenotypes: MIM:613161

GenCC curated gene-disease

Disease	Classification	Inheritance
beta-ureidopropionase deficiency	Strong	Autosomal recessive

Mondo (1): beta-ureidopropionase deficiency (MONDO:0013164)

Orphanet (1): Beta-ureidopropionase deficiency (Orphanet:65287)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000048	Bifid scrotum
HP:0000252	Microcephaly
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001319	Neonatal hypotonia
HP:0001332	Dystonia
HP:0001510	Growth delay
HP:0001942	Metabolic acidosis
HP:0002023	Anal atresia
HP:0002059	Cerebral atrophy
HP:0002133	Status epilepticus
HP:0002151	Increased circulating lactate concentration
HP:0002167	Abnormal speech pattern
HP:0002188	Delayed CNS myelination
HP:0002521	Hypsarrhythmia
HP:0002539	Cortical dysplasia
HP:0002650	Scoliosis
HP:0002836	Bladder exstrophy
HP:0003593	Infantile onset
HP:0007185	Loss of consciousness
HP:0012448	Delayed myelination
HP:0034595	Elevated circulating N-carbamoyl-beta-alanine concentration
HP:6000082	Reduced hepatic beta-ureidopropionase activity
HP:6000118	Elevated urinary dihydrouracil level

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002481_6	Acne (severe)	6.000000e-07
GCST008521_1	Bitter beverage consumption	8.000000e-07
GCST008524_7	Bitter non-alcoholic beverage consumption	8.000000e-08
GCST009205_15	Supramarginal gyrus volume	9.000000e-06
GCST011124_11	Caffeine consumption from tea	7.000000e-29
GCST011125_13	Caffeine consumption from coffee	2.000000e-13
GCST012020_512	Serum metabolite levels	3.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010089	bitter beverage consumption measurement
EFO:0010093	bitter non-alcoholic beverage consumption measurement
EFO:0010091	tea consumption measurement
EFO:0006781	coffee consumption measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563210	Beta-Ureidopropionase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3430874 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2070474	ADORA2A-AS1, UPB1		0.00	0
rs143493067	UPB1		0.00	0

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
Benzo(a)pyrene	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	increases expression, decreases expression	2
OTX015	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
obeticholic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Endosulfan	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Methotrexate	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	decreases expression	1
Oxygen	increases expression	1
Phenobarbital	decreases expression	1
Toxaphene	affects response to substance	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Vincristine	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.