UGGT1

Summary

UGGT1 (UDP-glucose glycoprotein glucosyltransferase 1, HGNC:15663) is a protein-coding gene on chromosome 2q14.3, encoding UDP-glucose:glycoprotein glucosyltransferase 1 (Q9NYU2). Recognizes glycoproteins with minor folding defects.

UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that selectively reglucosylates unfolded glycoproteins, thus providing quality control for protein transport out of the ER.

Source: NCBI Gene 56886 — RefSeq curated summary.

At a glance

• Gene–disease (curated): disorder of protein N-glycosylation (Moderate, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 252 total — 9 pathogenic
• Phenotypes (HPO): 130
• Druggable target: yes
• MANE Select transcript: NM_020120

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15663
Approved symbol	UGGT1
Name	UDP-glucose glycoprotein glucosyltransferase 1
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	HUGT1
Ensembl gene	ENSG00000136731
Ensembl biotype	protein_coding
OMIM	605897
Entrez	56886

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000259253, ENST00000376723, ENST00000418197, ENST00000430075, ENST00000438277, ENST00000465836, ENST00000488439, ENST00000860373, ENST00000860374, ENST00000860375, ENST00000933134, ENST00000933135, ENST00000933136, ENST00000933137, ENST00000933138, ENST00000969482

RefSeq mRNA: 1 — MANE Select: NM_020120 NM_020120

CCDS: CCDS2154

Canonical transcript exons

ENST00000259253 — 41 exons

Exon	Start	End
ENSE00001206093	128091200	128091415
ENSE00001946821	128189717	128195677
ENSE00003460214	128152784	128152904
ENSE00003463929	128156392	128156415
ENSE00003477335	128123186	128123246
ENSE00003480644	128179786	128179870
ENSE00003501229	128145803	128145967
ENSE00003509827	128138717	128138852
ENSE00003516336	128121199	128121298
ENSE00003518148	128186683	128186799
ENSE00003521707	128178468	128178569
ENSE00003522570	128183675	128183789
ENSE00003522978	128115124	128115220
ENSE00003525243	128097429	128097564
ENSE00003532663	128170288	128170390
ENSE00003544963	128127361	128127452
ENSE00003547560	128155489	128155587
ENSE00003560578	128180890	128181072
ENSE00003564200	128182130	128182290
ENSE00003568994	128164730	128164825
ENSE00003569148	128133141	128133260
ENSE00003589735	128107938	128108068
ENSE00003594219	128174773	128174858
ENSE00003594598	128134876	128134961
ENSE00003598153	128176814	128176898
ENSE00003599063	128120356	128120456
ENSE00003603339	128171205	128171284
ENSE00003604772	128172573	128172762
ENSE00003610451	128157252	128157346
ENSE00003610970	128177832	128177920
ENSE00003622026	128143094	128143225
ENSE00003654071	128161138	128161268
ENSE00003665209	128103932	128104014
ENSE00003668282	128116265	128116343
ENSE00003672767	128159514	128159720
ENSE00003676287	128160460	128160591
ENSE00003683148	128173781	128173939
ENSE00003683505	128113084	128113258
ENSE00003688676	128109634	128109746
ENSE00003691149	128187449	128187614
ENSE00003693269	128129029	128129179

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 94.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.1474 / max 307.4859, expressed in 1823 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22464	25.0725	1814
22465	12.7387	1780
22480	0.1844	101
22481	0.1035	49
22479	0.0148	4
22477	0.0123	3
22476	0.0072	4
22478	0.0058	3
22475	0.0048	3
22474	0.0033	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.09	gold quality
stromal cell of endometrium	CL:0002255	93.62	gold quality
epithelium of nasopharynx	UBERON:0001951	93.19	gold quality
pylorus	UBERON:0001166	93.14	gold quality
visceral pleura	UBERON:0002401	92.97	gold quality
endothelial cell	CL:0000115	92.66	gold quality
cardia of stomach	UBERON:0001162	92.55	gold quality
corpus epididymis	UBERON:0004359	92.13	gold quality
sural nerve	UBERON:0015488	92.06	gold quality
pericardium	UBERON:0002407	92.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.82	gold quality
parietal pleura	UBERON:0002400	91.81	gold quality
tonsil	UBERON:0002372	91.77	gold quality
superior surface of tongue	UBERON:0007371	91.44	gold quality
parotid gland	UBERON:0001831	91.16	gold quality
tendon	UBERON:0000043	91.15	gold quality
germinal epithelium of ovary	UBERON:0001304	91.00	gold quality
pleura	UBERON:0000977	90.80	gold quality
colonic mucosa	UBERON:0000317	90.65	gold quality
colonic epithelium	UBERON:0000397	90.57	gold quality
trabecular bone tissue	UBERON:0002483	90.57	gold quality
tibia	UBERON:0000979	90.40	gold quality
urethra	UBERON:0000057	90.18	gold quality
middle temporal gyrus	UBERON:0002771	89.96	gold quality
superficial temporal artery	UBERON:0001614	89.77	gold quality
saphenous vein	UBERON:0007318	89.73	gold quality
body of tongue	UBERON:0011876	89.67	gold quality
jejunum	UBERON:0002115	89.66	gold quality
synovial joint	UBERON:0002217	89.48	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.81
E-GEOD-106540	no	297.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

220 targeting UGGT1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817

Literature-anchored findings (GeneRIF, showing 18)

• The substrate binding specificity (PMID:12682060)
• the amino-terminal 80% of HUGT1 is required for activation of the catalytic domain (PMID:12913004)
• overexpression leads to increase in production of recombinant proteins; gene targeting (PMID:19466607)
• UGT1 aids in the folding of sequential domain-containing proteins such as prosaposin. (PMID:20498017)
• The UGGT1 is a well-documented enzyme which functions as a folding sensor in the endoplasmic reticulum, by the virtue of its ability to transfer a glucose residue to non-glucosylated high-mannose-type glycans of immature glycoproteins. (PMID:24415556)
• A novel UGGT1- and p97-dependent protein quality checkpoint is shown. This checkpoint is alerted to prevent secretion of a polypeptide that passes the luminal quality control scrutiny by BiP and CNX but contains an intramembrane ionizable residue. (PMID:25694454)
• Results indicate that glycan structures are similar to endogenous glycans at low expression levels of uridine 5’-diphosphate-glucose: glycoprotein glucosyltransferase (UGGT1). (PMID:25935482)
• Kyte-Doolittle analysis as well as homology modeling revealed a cluster of hydrophobic amino acids that may be functional in the folding sensing mechanism of HUGT1 (PMID:26196150)
• In this study, we aimed to clarify the contribution of the noncatalytic domains by comparing activities of truncated forms of recombinant HUGT1/HUGT2 and HUGT1/HUGT2 chimeras with full-length enzymes. (PMID:27496766)
• The results demonstrated that FAM5C is an N-glycosylated protein, and N-glycosylation by UGGT1 is necessary for the secretion of FAM5C. (PMID:28351617)
• The authors identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle that is known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. The results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with p (PMID:28425917)
• These findings provide important insight on the role of unfolded protein response (UPR) and host UGGT1 in regulating RNA virus replication and pathogenicity. (PMID:28545059)
• both vIL-6 and VKORC1v2 interact with calnexin cycle proteins UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), which catalyzes monoglucosylation of N-glycans, and oppositely acting glucosidase II (GlucII), and that vIL-6 can promote protein folding. (PMID:28878084)
• Glycan dependent refolding activity of ER glucosyltransferase (UGGT). (PMID:32858085)
• Quantitative glycoproteomics reveals cellular substrate selectivity of the ER protein quality control sensors UGGT1 and UGGT2. (PMID:33320095)
• Polypeptide N-acetylgalactosaminyltransferase 18 retains in endoplasmic reticulum depending on its luminal regions interacting with ER resident UGGT1, PLOD3 and LPCAT1. (PMID:33909026)
• The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I. (PMID:37345806)
• Rescue of secretion of rare-disease-associated misfolded mutant glycoproteins in UGGT1 knock-out mammalian cells. (PMID:38272446)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	uggt1	ENSDARG00000054746
mus_musculus	Uggt1	ENSMUSG00000037470
rattus_norvegicus	Uggt1	ENSRNOG00000014901
drosophila_melanogaster	Uggt	FBGN0014075
caenorhabditis_elegans	uggt-2	WBGENE00009178
caenorhabditis_elegans		WBGENE00018604

Paralogs (1): UGGT2 (ENSG00000102595)

Protein

Protein identifiers

UDP-glucose:glycoprotein glucosyltransferase 1 — Q9NYU2 (reviewed: Q9NYU2)

Alternative names: UDP–Glc:glycoprotein glucosyltransferase, UDP-glucose ceramide glucosyltransferase-like 1

All UniProt accessions (5): E2QRN8, Q9NYU2, F8WCE6, F8WCI2, H7BZG0

UniProt curated annotations — full annotation on UniProt →

Function. Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic reticulum. Reglucosylated proteins are recognized by calreticulin for recycling to the endoplasmic reticulum and refolding or degradation.

Subunit / interactions. Monomer as well as in a tight complex with SELENOF. Interacts with METTL23. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX.

Subcellular location. Endoplasmic reticulum lumen. Endoplasmic reticulum-Golgi intermediate compartment.

Tissue specificity. Higher levels in pancreas, skeletal muscle, kidney, and brain. Low levels in lung and heart.

Activity regulation. Catalytic activity is enhanced by complex formation with SELENOF.

Domain organisation. The N-terminal non-catalytic domain is assumed to mediate recognition of proteins with partial folding defects.

Induction. By tunicamycin and A23187. Induced 3-4 fold 10 hours after treatment.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NYU2-1	1	yes
Q9NYU2-2	2

RefSeq proteins (1): NP_064505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009448	UDP-g_GGtrans	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR040497	Glyco_transf_24	Domain
IPR040525	UGGT_TRXL_4	Domain
IPR040692	UGGT_TRXL_3	Domain
IPR040693	UGGT_TRXL_1	Domain
IPR040694	UGGT_TRXL_2	Domain

Pfam: PF06427, PF18400, PF18401, PF18402, PF18403, PF18404

Catalyzed reactions (Rhea), 1 shown:

• N(4)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein] (N-glucan mannose isomer 9A1,2,3B1,2,3) + UDP-alpha-D-glucose = N(4)-(alpha-D-Glc-(1->3)-alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein] + UDP + H(+) (RHEA:61304)

UniProt features (18 total): mutagenesis site 8, region of interest 2, glycosylation site 2, signal peptide 1, chain 1, sequence conflict 1, short sequence motif 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYU2-F1	83.97	0.43

Functional residue map

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

Post-translational modifications (1): 1277

Glycosylation sites (2): 536, 1228

Mutagenesis-validated functional residues (8):

Position	Phenotype
1452–1457	inactive.
1452	inactive.
1453	4% active.
1454	inactive.
1455	2% active.
1456	41% active.
1457	7% active.
1358	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-901032	ER Quality Control Compartment (ERQC)

MSigDB gene sets: 228 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, AHRARNT_01, E2F_Q4, MULLIGHAN_NPM1_SIGNATURE_3_UP, E2F4DP1_01, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, E2F1DP1_01, GOBP_PROTEIN_MATURATION, E2F1DP2_01, GGAANCGGAANY_UNKNOWN

GO Biological Process (5): obsolete protein N-linked glycosylation via asparagine (GO:0018279), ‘de novo’ post-translational protein folding (GO:0051084), endoplasmic reticulum mannose trimming (GO:1904380), obsolete protein glycosylation (GO:0006486), UDP-glucosylation (GO:0097359)

GO Molecular Function (5): UDP-glucose:glycoprotein glucosyltransferase activity (GO:0003980), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), protein-containing complex (GO:0032991), endoplasmic reticulum quality control compartment (GO:0044322), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Calnexin/calreticulin cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
endoplasmic reticulum	2
‘de novo’ protein folding	1
protein alpha-1,2-demannosylation	1
endoplasmic reticulum quality control compartment	1
UDP-alpha-D-glucose metabolic process	1
UDP-glucosyltransferase activity	1
UDP-glucosylation	1
binding	1
catalytic activity	1
transferase activity	1
endomembrane system	1
intracellular organelle lumen	1
cellular_component	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UGGT1	SELENOF	O60613	986
UGGT1	HSP90B1	P14625	941
UGGT1	CANX	P27824	898
UGGT1	GXYLT2	A0PJZ3	895
UGGT1	GXYLT1	Q4G148	895
UGGT1	CALR	P27797	836
UGGT1	MOGS	Q13724	815
UGGT1	ERLEC1	Q96DZ1	781
UGGT1	PDIA4	P13667	776
UGGT1	HYOU1	Q9Y4L1	745
UGGT1	EDEM1	Q92611	742
UGGT1	OS9	Q13438	739
UGGT1	MAN1B1	Q9UKM7	729
UGGT1	PDIA3	P30101	691
UGGT1	GANAB	Q14697	690

IntAct

133 interactions, top by confidence:

A	B	Type	Score
ACBD6	NMT2	psi-mi:“MI:0914”(association)	0.870
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
SLCO4C1	CLGN	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
HSD3B1	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
UGGT2	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
VPS51	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
TRPM5	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
RYR3	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
ARAP3	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
UGGT1	SF3B1	psi-mi:“MI:0914”(association)	0.350
NA	IPO5	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
RAB27A	DKC1	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6		psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350

BioGRID (323): UGGT1 (Affinity Capture-MS), UGGT1 (Affinity Capture-Western), UGGT1 (Affinity Capture-MS), SSU72 (Co-fractionation), UGGT1 (Affinity Capture-MS), UGGT1 (Proximity Label-MS), UGGT1 (Proximity Label-MS), DNMT3B (Affinity Capture-MS), LGALS3BP (Affinity Capture-MS), RAD51 (Affinity Capture-MS), DPF2 (Affinity Capture-MS), STX3 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), REPS2 (Affinity Capture-MS), CEPT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1N5Y4, A3KPF5, A8WG88, O22925, O80977, P08003, P11598, P13667, P30040, P30101, P32474, P38659, P52555, P52588, P57759, P81623, P81628, P93026, P93484, Q0E0I1, Q0JD42, Q0WL80, Q17688, Q2KIL5, Q43116, Q498R3, Q56ZQ3, Q5FVM7, Q5I0H9, Q5R5L3, Q5RDG4, Q5WA72, Q66GQ3, Q67IX6, Q6GNG3, Q6NRT6, Q6P5E4, Q7JW12, Q7XRB5, Q8IXB1

Diamond homologs: Q09140, Q09332, Q6P5E4, Q8T191, Q9JLA3, Q9NYU1, Q9NYU2, P22023, Q0WL80

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-549132	5	30.4×	6e-05
Transport of vitamins, nucleosides, and related molecules	6	13.1×	6e-04
SLC transporter disorders	7	11.4×	3e-04
R-HSA-425366	6	8.7×	4e-03
SLC-mediated transmembrane transport	17	8.1×	2e-08
Disorders of transmembrane transporters	7	7.8×	3e-03
Transport of small molecules	22	4.4×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
sodium-independent organic anion transport	7	52.4×	3e-08
obsolete organic anion transport	5	26.8×	3e-04
bile acid and bile salt transport	5	21.6×	8e-04
transmembrane transport	9	10.1×	2e-04
transport across blood-brain barrier	7	8.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	0
Uncertain significance	178
Likely benign	8
Benign	10

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
4070982	NM_020120.4(UGGT1):c.752del (p.Lys251fs)	Pathogenic
4280138	NM_020120.4(UGGT1):c.381_384del (p.Ser126_Tyr127insTer)	Pathogenic
4280139	NM_020120.4(UGGT1):c.1168_1191del (p.Asp390_Gly397del)	Pathogenic
4280140	NM_020120.4(UGGT1):c.3464A>G (p.Gln1155Arg)	Pathogenic
4280141	NM_020120.4(UGGT1):c.978_979del (p.Ser327fs)	Pathogenic
4280142	UGGT1, 1-BP DUP, 4081C	Pathogenic
4280143	NM_020120.4(UGGT1):c.2168T>C (p.Phe723Ser)	Pathogenic
4280145	NM_020120.4(UGGT1):c.3815G>A (p.Arg1272His)	Pathogenic
4280146	NM_020120.4(UGGT1):c.2132C>T (p.Ala711Val)	Pathogenic

SpliceAI

6071 predictions. Top by Δscore:

Variant	Effect	Δscore
2:128097428:GGA:G	acceptor_gain	1.0000
2:128103930:A:AG	acceptor_gain	1.0000
2:128103931:G:GG	acceptor_gain	1.0000
2:128103931:GT:G	acceptor_gain	1.0000
2:128103931:GTGA:G	acceptor_gain	1.0000
2:128109743:AAAG:A	donor_loss	1.0000
2:128109744:AAGG:A	donor_loss	1.0000
2:128109747:GTAG:G	donor_loss	1.0000
2:128109748:T:A	donor_loss	1.0000
2:128113081:CAGAC:C	acceptor_loss	1.0000
2:128113082:A:AG	acceptor_gain	1.0000
2:128113083:G:GG	acceptor_gain	1.0000
2:128113083:GACCC:G	acceptor_gain	1.0000
2:128113225:C:T	donor_gain	1.0000
2:128113254:TATTT:T	donor_gain	1.0000
2:128113255:ATTT:A	donor_gain	1.0000
2:128113256:TTT:T	donor_gain	1.0000
2:128113256:TTTG:T	donor_loss	1.0000
2:128113257:TT:T	donor_gain	1.0000
2:128113258:TGTA:T	donor_loss	1.0000
2:128113259:G:GA	donor_loss	1.0000
2:128113259:G:GG	donor_gain	1.0000
2:128113260:TA:T	donor_loss	1.0000
2:128113261:AA:A	donor_loss	1.0000
2:128115119:TGCA:T	acceptor_loss	1.0000
2:128115120:GCA:G	acceptor_loss	1.0000
2:128115121:CA:C	acceptor_loss	1.0000
2:128115122:A:AC	acceptor_loss	1.0000
2:128115122:A:AG	acceptor_gain	1.0000
2:128115123:G:GA	acceptor_gain	1.0000

AlphaMissense

10323 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:128115178:A:G	K251E	1.000
2:128115180:G:C	K251N	1.000
2:128115180:G:T	K251N	1.000
2:128115190:T:C	Y255H	1.000
2:128173832:G:C	G1116R	1.000
2:128173840:C:G	C1118W	1.000
2:128173875:T:C	L1130P	1.000
2:128173926:T:A	V1147D	1.000
2:128173936:T:A	N1150K	1.000
2:128173936:T:G	N1150K	1.000
2:128173938:T:C	L1151P	1.000
2:128174773:G:C	G1152R	1.000
2:128174774:G:A	G1152D	1.000
2:128174774:G:T	G1152V	1.000
2:128179835:T:A	W1289R	1.000
2:128179835:T:C	W1289R	1.000
2:128180950:T:A	W1321R	1.000
2:128180950:T:C	W1321R	1.000
2:128180952:G:C	W1321C	1.000
2:128180952:G:T	W1321C	1.000
2:128180959:T:A	W1324R	1.000
2:128180959:T:C	W1324R	1.000
2:128180961:G:C	W1324C	1.000
2:128180961:G:T	W1324C	1.000
2:128180963:T:C	L1325P	1.000
2:128180987:G:C	R1333P	1.000
2:128180995:T:A	W1336R	1.000
2:128180995:T:C	W1336R	1.000
2:128180997:G:C	W1336C	1.000
2:128180997:G:T	W1336C	1.000

dbSNP variants (sampled 300 via entrez): RS1000043206 (2:128159316 G>T), RS1000048036 (2:128188809 C>T), RS1000065762 (2:128097759 G>A), RS1000075834 (2:128159167 T>C), RS1000078811 (2:128117796 G>A,T), RS1000095844 (2:128118226 C>T), RS1000110854 (2:128137463 G>C), RS1000162120 (2:128188409 T>A), RS1000199549 (2:128105386 C>G,T), RS1000219264 (2:128104467 A>G), RS1000251091 (2:128153165 A>G), RS1000329255 (2:128099421 G>C), RS1000340113 (2:128124082 A>C,T), RS1000346190 (2:128140474 A>T), RS1000367964 (2:128165847 C>A,T)

Disease associations

OMIM: gene MIM:605897 | disease phenotypes: MIM:143890, MIM:621381

GenCC curated gene-disease

Disease	Classification	Inheritance
disorder of protein N-glycosylation	Moderate	Autosomal recessive

Mondo (3): hypercholesterolemia, familial, 1 (MONDO:0007750), congenital disorder of glycosylation, type IIcc (MONDO:0980705), disorder of protein N-glycosylation (MONDO:0017740)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

130 total (30 of 130 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000062	Ambiguous genitalia
HP:0000126	Hydronephrosis
HP:0000219	Thin upper lip vermilion
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000473	Torticollis
HP:0000480	Retinal coloboma
HP:0000486	Strabismus
HP:0000582	Upslanted palpebral fissure
HP:0000588	Optic disc coloboma
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000717	Autism

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008762_6	Intake of sweets	9.000000e-06
GCST009391_654	Metabolite levels	7.000000e-07
GCST90002409_46	Childhood body mass index	4.000000e-06
GCST90013466_25	Height	2.000000e-06
GCST90013466_66	Height	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010158	sugar consumption measurement
EFO:0010507	lactose measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725043 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.36	Kd	43.45	nM	CHEMBL5653589
7.36	ED50	43.45	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 10 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149726: Binding affinity to human UGGT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0435	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Nickel	increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
geldanamycin	increases expression	1
sodium arsenate	decreases expression	1
arsenite	decreases reaction, affects binding	1
dinophysistoxin 1	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arecoline	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	affects expression	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Vitallium	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	increases expression	1
beta-Naphthoflavone	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652768	Binding	Binding affinity to human UGGT1 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab