UGP2

Summary

UGP2 (UDP-glucose pyrophosphorylase 2, HGNC:12527) is a protein-coding gene on chromosome 2p15, encoding UTP–glucose-1-phosphate uridylyltransferase (Q16851). UTP–glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen. It is a selective cancer dependency (DepMap: 25.6% of cell lines).

The enzyme encoded by this gene is an important intermediary in mammalian carbohydrate interconversions. It transfers a glucose moiety from glucose-1-phosphate to MgUTP and forms UDP-glucose and MgPPi. In liver and muscle tissue, UDP-glucose is a direct precursor of glycogen; in lactating mammary gland it is converted to UDP-galactose which is then converted to lactose. The eukaryotic enzyme has no significant sequence similarity to the prokaryotic enzyme. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7360 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 83 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 90 total
• Phenotypes (HPO): 32
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 25.6% of screened cell lines
• MANE Select transcript: NM_006759

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12527
Approved symbol	UGP2
Name	UDP-glucose pyrophosphorylase 2
Location	2p15
Locus type	gene with protein product
Status	Approved
Aliases	UGPP1, SVUGP2
Ensembl gene	ENSG00000169764
Ensembl biotype	protein_coding
OMIM	191760
Entrez	7360

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 21 protein_coding, 15 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000337130, ENST00000394417, ENST00000445915, ENST00000465515, ENST00000466642, ENST00000467400, ENST00000467648, ENST00000467999, ENST00000472047, ENST00000475462, ENST00000475550, ENST00000480679, ENST00000482668, ENST00000483108, ENST00000483461, ENST00000484056, ENST00000484142, ENST00000487042, ENST00000487469, ENST00000487640, ENST00000488245, ENST00000491621, ENST00000493222, ENST00000494536, ENST00000495020, ENST00000496334, ENST00000497510, ENST00000497883, ENST00000613823, ENST00000626380, ENST00000627474, ENST00000640075, ENST00000676780, ENST00000676870, ENST00000677841, ENST00000678298, ENST00000678951, ENST00000678974, ENST00000679256, ENST00000866555, ENST00000866556, ENST00000866557, ENST00000866558, ENST00000866559, ENST00000934101

RefSeq mRNA: 8 — MANE Select: NM_006759 NM_001001521, NM_001377524, NM_001377525, NM_001377526, NM_001377527, NM_001377528, NM_001377529, NM_006759

CCDS: CCDS1875, CCDS42690

Canonical transcript exons

ENST00000337130 — 10 exons

Exon	Start	End
ENSE00001165982	63890081	63890185
ENSE00001266184	63887402	63887644
ENSE00001926783	63841896	63842204
ENSE00003459114	63886341	63886538
ENSE00003546033	63882466	63882651
ENSE00003560050	63891120	63891560
ENSE00003583546	63883960	63884093
ENSE00003645549	63856306	63856433
ENSE00003649665	63885589	63885886
ENSE00003665935	63857829	63857936

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.2446 / max 1116.3290, expressed in 1819 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20547	37.6023	1725
20543	10.3858	1748
20544	6.8979	1586
20542	6.2918	1621
20548	2.7371	893
20546	1.5286	685
20552	0.2654	65
20549	0.2171	86
20550	0.1499	59
20551	0.1004	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.56	gold quality
biceps brachii	UBERON:0001507	99.55	gold quality
body of tongue	UBERON:0011876	99.48	gold quality
heart right ventricle	UBERON:0002080	99.38	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.38	gold quality
colonic mucosa	UBERON:0000317	99.37	gold quality
secondary oocyte	CL:0000655	99.35	gold quality
diaphragm	UBERON:0001103	99.18	gold quality
oocyte	CL:0000023	99.14	gold quality
cartilage tissue	UBERON:0002418	99.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.02	gold quality
gastrocnemius	UBERON:0001388	98.99	gold quality
parotid gland	UBERON:0001831	98.99	gold quality
pons	UBERON:0000988	98.92	gold quality
right lobe of liver	UBERON:0001114	98.89	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.87	gold quality
liver	UBERON:0002107	98.85	gold quality
rectum	UBERON:0001052	98.84	gold quality
muscle of leg	UBERON:0001383	98.84	gold quality
triceps brachii	UBERON:0001509	98.84	gold quality
mucosa of transverse colon	UBERON:0004991	98.81	gold quality
gluteal muscle	UBERON:0002000	98.74	gold quality
synovial joint	UBERON:0002217	98.72	gold quality
postcentral gyrus	UBERON:0002581	98.72	gold quality
germinal epithelium of ovary	UBERON:0001304	98.69	gold quality
skin of hip	UBERON:0001554	98.66	gold quality
orbitofrontal cortex	UBERON:0004167	98.64	gold quality
popliteal artery	UBERON:0002250	98.60	gold quality
tibial artery	UBERON:0007610	98.60	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	1252.36
E-GEOD-125970	yes	28.77
E-CURD-46	yes	23.76
E-MTAB-9388	yes	13.19
E-HCAD-1	yes	10.18
E-CURD-120	no	29.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TCF12

miRNA regulators (miRDB)

38 targeting UGP2, 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-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-6747-3P	97.73	64.84	1596

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen, and hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-alpha glucan branching enzyme (GBE1) (PMID:20300197)
• The crystal structure was determined and shown to form octamers through end-to-end and side-by-side interactions. Mutagenesis studies showed that both dissociation of octamers and mutations of the latch loop can significantly affect the activity. (PMID:22132858)
• This study provides clear evidence that the octameric state is a prerequisite for activity in the uridine diphosphate-glucose pyrophosphorylase. (PMID:23254995)
• High UGP2 expression is associated with malignant pancreatic lesions. (PMID:29347944)
• Identification of UGP2 as a progression marker that promotes cell growth and motility in human glioma. (PMID:30816613)
• Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases. (PMID:31820119)
• Defects in Galactose Metabolism and Glycoconjugate Biosynthesis in a UDP-Glucose Pyrophosphorylase-Deficient Cell Line Are Reversed by Adding Galactose to the Growth Medium. (PMID:32188137)
• Low UGP2 Expression Is Associated with Tumour Progression and Predicts Poor Prognosis in Hepatocellular Carcinoma. (PMID:32733617)
• UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth. (PMID:34330832)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ugp2a	ENSDARG00000005578
danio_rerio	ugp2b	ENSDARG00000008200
mus_musculus	Ugp2	ENSMUSG00000001891
rattus_norvegicus	Ugp2	ENSRNOG00000008079
drosophila_melanogaster	UGP	FBGN0035978
caenorhabditis_elegans		WBGENE00010665

Paralogs (2): UAP1 (ENSG00000117143), UAP1L1 (ENSG00000197355)

Protein

Protein identifiers

UTP–glucose-1-phosphate uridylyltransferase — Q16851 (reviewed: Q16851)

Alternative names: UDP-glucose pyrophosphorylase

All UniProt accessions (21): A0A087WYS1, A0A140VKE1, A0A7I2V2Q3, A0A7I2V4T0, A0A7I2V676, A0A7I2YQ74, C9J3M0, C9J6Q0, C9JNZ1, C9JQU9, C9JTZ5, C9JUW1, C9JVG3, C9JWG0, E7EUC7, Q16851, F2Z3H1, F2Z3P4, F8WC70, F8WDA2, H7C500

UniProt curated annotations — full annotation on UniProt →

Function. UTP–glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen.

Subunit / interactions. Homooctamer.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in various brain regions. Expressed in amygdala, anterior cingulate cortex, caudate, cerebellar hemisphere, cerebellum, cortex, frontal cortex, hippocampus, hypothalamus, nucleus accumbens, putamen, spinal cord and substantia nigra. Also widely expressed among other tissues, including liver, heart, placenta, lung, kidney, pancreas and skeletal muscle.

Disease relevance. Developmental and epileptic encephalopathy 83 (DEE83) [MIM:618744] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE83 is an autosomal recessive form characterized by onset of frequent, intractable seizures in the first days to months of life. Affected individuals have profound developmental delay with no motor or language skill acquisition, and poor or absent visual tracking. Many patients die in the first years of life. The disease is caused by variants affecting the gene represented in this entry. A recurrent, pathogenic variant affecting the translation initiation codon of isoform 2 has been found in multiple DEE83 families. The variant results in the absence of isoform 2 and leads to reduced levels of functional UGP2 enzyme in neural stem cells. The absence of isoform 2 is compensated by an increased abundance of a functional isoform 1, carrying variant p.Met12Val, which may explain the survival of the patients. A complete absence of functional UGP2 in all cells would be embryonic lethal.

Pathway. Glycan biosynthesis; glycogen biosynthesis.

Similarity. Belongs to the UDPGP type 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16851-1	1, Muscle-II, long	yes
Q16851-2	2, Muscle-I, short

RefSeq proteins (8): NP_001001521, NP_001364453, NP_001364454, NP_001364455, NP_001364456, NP_001364457, NP_001364458, NP_006750* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002618	UDPGP_fam	Family
IPR016267	UDPGP_trans	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF01704

Enzyme classification (BRENDA):

• EC 2.7.7.9 — UTP-glucose-1-phosphate uridylyltransferase (BRENDA: 80 organisms, 147 substrates, 90 inhibitors, 203 Km, 45 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ALPHA-D-GLUCOSE 1-PHOSPHATE	0.01–3.28	45
DIPHOSPHATE	0.027–60	37
UTP	0.0075–0.56	34
UDP-GLUCOSE	0.0017–57	31
TTP	0.35–2	4
DTTP	0.0242–0.366	3
ALPHA-D-GALACTOSE 1-PHOSPHATE	0.09–10	2
ATP	0.336–0.68	2
CTP	0.276–0.429	2
D-GLUCOSE-1-PHOSPHATE	0.19–0.83	2
GTP	0.184–0.299	2
MG2+	0.58–1.11	2
UDP-GALACTOSE	0.26–0.42	2
FARNESYL TRIPHOSPHATE	0.32	1
GERANYL TRIPHOSPHATE	0.21	1

Catalyzed reactions (Rhea), 1 shown:

• alpha-D-glucose 1-phosphate + UTP + H(+) = UDP-alpha-D-glucose + diphosphate (RHEA:19889)

UniProt features (102 total): strand 27, helix 24, binding site 12, sequence conflict 10, mutagenesis site 9, modified residue 8, turn 4, region of interest 2, sequence variant 2, chain 1, splice variant 1, active site 1, initiator methionine 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4R7P	X-RAY DIFFRACTION	3.35
3R3I	X-RAY DIFFRACTION	3.57
3R2W	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16851-F1	88.68	0.63

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 (1): 396

Ligand- & substrate-binding residues (12): 223; 251–253; 253; 253; 330; 396; 113–116; 115–116; 127; 127; 190; 222

Post-translational modifications (8): 2, 2, 13, 426, 434, 438, 448, 461

Mutagenesis-validated functional residues (9):

Position	Phenotype
123	no significant loss of activity.
218	no significant loss of activity.
266	no significant loss of activity.
333	loss of activity; possibly due to folding defect.
389	no significant loss of activity.
391	loss of activity; possibly due to folding defect.
422	no significant loss of activity.
445	no significant loss of activity.
502–503	abolishes oligomerization and significantly increases enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-173599	Formation of the active cofactor, UDP-glucuronate
R-HSA-3322077	Glycogen synthesis

MSigDB gene sets: 310 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, REACTOME_BIOLOGICAL_OXIDATIONS, MORF_MBD4, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, SMITH_TERT_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, CAIRO_HEPATOBLASTOMA_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, KEGG_STARCH_AND_SUCROSE_METABOLISM

GO Biological Process (7): glycogen metabolic process (GO:0005977), glycogen biosynthetic process (GO:0005978), UDP-alpha-D-glucose metabolic process (GO:0006011), UDP-glucuronate biosynthetic process (GO:0006065), brain development (GO:0007420), glucose 1-phosphate metabolic process (GO:0019255), energy derivation by oxidation of organic compounds (GO:0015980)

GO Molecular Function (10): UTP:glucose-1-phosphate uridylyltransferase activity (GO:0003983), D-glucose binding (GO:0005536), pyrimidine ribonucleotide binding (GO:0032557), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), UTP-monosaccharide-1-phosphate uridylyltransferase activity (GO:0051748), uridylyltransferase activity (GO:0070569)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Glucuronidation	1
Glycogen metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
energy reserve metabolic process	1
glucan metabolic process	1
glycogen metabolic process	1
glucan biosynthetic process	1
nucleotide-sugar metabolic process	1
nucleotide-sugar biosynthetic process	1
carboxylic acid biosynthetic process	1
UDP-glucuronate metabolic process	1
central nervous system development	1
animal organ development	1
head development	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
generation of precursor metabolites and energy	1
UTP-monosaccharide-1-phosphate uridylyltransferase activity	1
monosaccharide binding	1
pyrimidine nucleotide binding	1
ribonucleotide binding	1
protein binding	1
cation binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
uridylyltransferase activity	1
nucleotidyltransferase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UGP2	PYGL	P06737	800
UGP2	PYGM	P11217	784
UGP2	PYGB	P11216	783
UGP2	UGDH	O60701	760
UGP2	GBE1	Q04446	760
UGP2	GPI	P06744	718
UGP2	GALE	Q14376	718
UGP2	GYS1	P13807	716
UGP2	PGM1	P36871	690
UGP2	GALK1	P51570	684
UGP2	GYS2	P54840	646
UGP2	AGL	P35573	643
UGP2	PGM2	Q96G03	629
UGP2	PASK	Q96RG2	611
UGP2	GALT	P07902	607

IntAct

57 interactions, top by confidence:

A	B	Type	Score
UGP2	UGP2	psi-mi:“MI:0915”(physical association)	0.800
UGP2	ARIH2	psi-mi:“MI:0915”(physical association)	0.780
ARIH2	UGP2	psi-mi:“MI:0915”(physical association)	0.780
GLRX3	UGP2	psi-mi:“MI:0915”(physical association)	0.560
UGP2	GLRX3	psi-mi:“MI:0915”(physical association)	0.560
UGP2	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
KLF11	UGP2	psi-mi:“MI:0915”(physical association)	0.560
SUN2	POTEF	psi-mi:“MI:0914”(association)	0.530
UGP2	GRB2	psi-mi:“MI:0915”(physical association)	0.400
UGP2	CBS	psi-mi:“MI:0915”(physical association)	0.370
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
APP	MGST3	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
DCAF15	ARNT	psi-mi:“MI:0914”(association)	0.350
SNX24	STRN	psi-mi:“MI:0914”(association)	0.350
GPSM1	BRD4	psi-mi:“MI:0914”(association)	0.350
HDAC7	ZMYM6	psi-mi:“MI:0914”(association)	0.350
	GAPDH	psi-mi:“MI:0914”(association)	0.350
CSAG2	CAMK2D	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): UGP2 (Two-hybrid), ARIH2 (Two-hybrid), GLRX3 (Two-hybrid), UGP2 (Affinity Capture-MS), UGP2 (Affinity Capture-MS), UGP2 (Affinity Capture-MS), UGP2 (Affinity Capture-MS), ARIH2 (Two-hybrid), UGP2 (Two-hybrid), UGP2 (Affinity Capture-RNA), ALDH16A1 (Co-fractionation), GK2 (Co-fractionation), HSPE1 (Co-fractionation), KHK (Co-fractionation), UGP2 (Co-fractionation)

ESM2 similar proteins: A2YGP6, F4I1L3, F4IY62, O22585, O35156, O64407, O64459, O64765, O65015, P10538, P19595, P31252, P32861, P43123, P49915, P55242, P57751, P78811, P79303, Q07130, Q09WE7, Q0GZS3, Q16851, Q18493, Q3THK7, Q43772, Q4V7C6, Q54YZ0, Q59KI0, Q5NBJ3, Q5RA96, Q5W915, Q5YLB4, Q5Z8Y4, Q6ZDQ1, Q8L743, Q8S6N5, Q8SSC5, Q8VWN6, Q91ZJ5

Diamond homologs: O35156, O59819, O64459, P08800, P19595, P32861, P38709, P57751, P78811, P79303, Q07130, Q16851, Q43772, Q54YZ0, Q59KI0, Q8SQS1, Q8SSC5, Q91ZJ5, Q9LKG7, Q9M9P3, Q9SDX3, Q49ZB5, Q28CH3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
UGP2	“down-regulates quantity”	“alpha-D-glucose 1-phosphate(2-)”	“chemical modification”
UGP2	“down-regulates quantity”	UTP(4-)	“chemical modification”
UGP2	“up-regulates quantity”	UDP-alpha-D-glucose(2-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	15
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2181 predictions. Top by Δscore:

Variant	Effect	Δscore
2:63856301:TTAAG:T	acceptor_loss	1.0000
2:63856304:A:AG	acceptor_gain	1.0000
2:63856305:G:GG	acceptor_gain	1.0000
2:63856431:GAGGT:G	donor_loss	1.0000
2:63856434:G:GA	donor_loss	1.0000
2:63856435:T:A	donor_loss	1.0000
2:63857824:CACA:C	acceptor_loss	1.0000
2:63857825:A:AG	acceptor_gain	1.0000
2:63857826:C:G	acceptor_gain	1.0000
2:63857826:CAGC:C	acceptor_loss	1.0000
2:63857827:A:AG	acceptor_gain	1.0000
2:63857827:A:T	acceptor_loss	1.0000
2:63857828:G:GA	acceptor_gain	1.0000
2:63857828:GC:G	acceptor_gain	1.0000
2:63857828:GCA:G	acceptor_gain	1.0000
2:63857828:GCAC:G	acceptor_gain	1.0000
2:63857828:GCACA:G	acceptor_gain	1.0000
2:63857933:TTCGG:T	donor_loss	1.0000
2:63857936:GGTAA:G	donor_loss	1.0000
2:63857937:G:GG	donor_gain	1.0000
2:63857937:GTAA:G	donor_loss	1.0000
2:63857938:TAA:T	donor_loss	1.0000
2:63882461:TTCA:T	acceptor_loss	1.0000
2:63882462:TCA:T	acceptor_loss	1.0000
2:63882463:CA:C	acceptor_loss	1.0000
2:63882464:A:AC	acceptor_loss	1.0000
2:63882464:A:AG	acceptor_gain	1.0000
2:63882465:G:GT	acceptor_gain	1.0000
2:63882465:GA:G	acceptor_gain	1.0000
2:63882465:GATT:G	acceptor_gain	1.0000

AlphaMissense

3353 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:63882548:T:C	L113P	1.000
2:63882552:T:A	N114K	1.000
2:63882552:T:G	N114K	1.000
2:63882553:G:C	G115R	1.000
2:63882553:G:T	G115C	1.000
2:63882554:G:A	G115D	1.000
2:63882554:G:T	G115V	1.000
2:63882562:G:A	G118R	1.000
2:63882562:G:C	G118R	1.000
2:63882563:G:A	G118E	1.000
2:63882591:A:C	K127N	1.000
2:63882591:A:T	K127N	1.000
2:63882592:A:C	S128R	1.000
2:63882594:T:A	S128R	1.000
2:63882594:T:G	S128R	1.000
2:63882622:T:C	F138L	1.000
2:63882624:T:A	F138L	1.000
2:63882624:T:G	F138L	1.000
2:63882626:T:C	L139P	1.000
2:63882632:T:C	L141P	1.000
2:63883988:T:A	V157D	1.000
2:63883994:T:C	L159P	1.000
2:63883997:T:A	V160D	1.000
2:63884000:T:C	L161S	1.000
2:63884007:C:A	N163K	1.000
2:63884007:C:G	N163K	1.000
2:63884008:T:C	S164P	1.000
2:63884009:C:T	S164F	1.000
2:63885677:G:C	G222R	1.000
2:63885678:G:A	G222D	1.000

dbSNP variants (sampled 300 via entrez): RS1000006071 (2:63847918 A>C,G), RS1000009855 (2:63861376 C>G), RS1000220156 (2:63885296 T>A), RS1000257615 (2:63847635 G>T), RS1000270514 (2:63891657 C>T), RS1000289339 (2:63849022 A>G), RS1000325740 (2:63875478 T>C), RS1000400198 (2:63890760 C>T), RS1000412914 (2:63841684 C>T), RS1000445388 (2:63878033 G>A,C,T), RS1000517250 (2:63846450 AAAAT>A), RS1000566421 (2:63840535 G>A), RS1000587179 (2:63847868 G>A), RS1000641088 (2:63841547 CGG>C,CGGG), RS1000660248 (2:63844392 G>A)

Disease associations

OMIM: gene MIM:191760 | disease phenotypes: MIM:618744

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 83	Strong	Autosomal recessive

Mondo (1): developmental and epileptic encephalopathy, 83 (MONDO:0032895)

Orphanet (0):

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000817	Reduced eye contact
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0002007	Frontal bossing
HP:0002033	Poor suck
HP:0002079	Hypoplasia of the corpus callosum
HP:0002120	Cerebral cortical atrophy
HP:0002187	Profound intellectual disability
HP:0002205	Recurrent respiratory infections
HP:0002273	Tetraparesis
HP:0002376	Developmental regression
HP:0002553	Highly arched eyebrow
HP:0002857	Genu valgum
HP:0005280	Depressed nasal bridge
HP:0007750	Hypoplasia of the fovea
HP:0008872	Feeding difficulties in infancy
HP:0008936	Axial hypotonia
HP:0009890	High anterior hairline
HP:0011344	Severe global developmental delay

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002595_21	Clozapine-induced agranulocytosis	7.000000e-06
GCST003670_5	Systolic blood pressure	6.000000e-06
GCST008810_33	Smoking initiation (ever regular vs never regular)	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067313 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, affects cotreatment	3
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	3
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Decitabine	affects expression, decreases expression, decreases reaction	2
Air Pollutants	affects expression, affects cotreatment, increases abundance, increases expression	2
Cadmium	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
Cyclosporine	increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression, decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, decreases expression, affects cotreatment	1
trichostatin A	decreases expression, increases expression	1
cinnamaldehyde	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
vanillin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652769	Binding	Binding affinity to human UGP2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7S1	SEES3-1V human UGP2, clone1	Embryonic stem cell	Male
CVCL_A7S2	SEES3-1V human UGP2, clone2	Embryonic stem cell	Male
CVCL_A7S3	SEES3-1V human UGP2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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