◎ Sugi Atlas

Atlas / Gene / UGT8

UGT8

gene
On this page

Summary

UGT8 (UDP glycosyltransferase 8, HGNC:12555) is a protein-coding gene on chromosome 4q26, encoding 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Q16880). Catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central nervous system and peripheral nervous system.

The protein encoded by this gene belongs to the UDP-glycosyltransferase family. It catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central and peripheral nervous systems. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 7368 — RefSeq curated summary.

At a glance

  • GWAS associations: 12
  • Clinical variants (ClinVar): 64 total
  • Druggable target: yes
  • MANE Select transcript: NM_001128174

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:12555
Approved symbolUGT8
NameUDP glycosyltransferase 8
Location4q26
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000174607
Ensembl biotypeprotein_coding
OMIM601291
Entrez7368

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000310836, ENST00000394511, ENST00000507710, ENST00000880012, ENST00000880013, ENST00000880014, ENST00000880015, ENST00000880016, ENST00000880017, ENST00000880018, ENST00000880019, ENST00000880020, ENST00000913294, ENST00000913295, ENST00000913296, ENST00000913297, ENST00000913298, ENST00000913299

RefSeq mRNA: 5 — MANE Select: NM_001128174 NM_001128174, NM_001322112, NM_001322113, NM_001322114, NM_003360

CCDS: CCDS3705

Canonical transcript exons

ENST00000310836 — 6 exons

ExonStartEnd
ENSE00001421081114598807114598974
ENSE00001842232114675925114678225
ENSE00002020131114622879114623702
ENSE00004282257114668085114668304
ENSE00004282258114663995114664137
ENSE00004282260114665680114665756

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 99.42.

FANTOM5 (CAGE): breadth broad, TPM avg 12.5443 / max 1194.0314, expressed in 627 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter IDTPM avgSamples expressed
493865.5075447
493822.9946378
493811.6907345
493831.1763106
493850.4536135
493870.166988
493880.154965
493890.133976
493900.122368
493840.101048

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
inferior vagus X ganglionUBERON:000536399.42gold quality
corpus callosumUBERON:000233699.21gold quality
subthalamic nucleusUBERON:000190698.94gold quality
superior vestibular nucleusUBERON:000722798.66gold quality
C1 segment of cervical spinal cordUBERON:000646998.61gold quality
ponsUBERON:000098898.60gold quality
spinal cordUBERON:000224098.54gold quality
lateral globus pallidusUBERON:000247698.33gold quality
substantia nigra pars reticulataUBERON:000196698.24gold quality
ventral tegmental areaUBERON:000269197.51gold quality
substantia nigra pars compactaUBERON:000196596.96gold quality
dorsal plus ventral thalamusUBERON:000189796.43gold quality
trigeminal ganglionUBERON:000167596.12gold quality
middle frontal gyrusUBERON:000270295.65gold quality
globus pallidusUBERON:000187595.20gold quality
lateral nuclear group of thalamusUBERON:000273695.20gold quality
medulla oblongataUBERON:000189695.15gold quality
medial globus pallidusUBERON:000247794.31gold quality
midbrainUBERON:000189194.20gold quality
renal medullaUBERON:000036293.85gold quality
substantia nigraUBERON:000203893.77gold quality
postcentral gyrusUBERON:000258193.52gold quality
parietal lobeUBERON:000187293.30gold quality
colonic mucosaUBERON:000031793.10gold quality
mucosa of sigmoid colonUBERON:000499392.84gold quality
Ammon’s hornUBERON:000195492.61gold quality
dorsal root ganglionUBERON:000004492.56gold quality
rectumUBERON:000105291.00gold quality
jejunal mucosaUBERON:000039990.71gold quality
putamenUBERON:000187490.29gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

ExperimentMarker?Max mean expression
E-HCAD-35yes85.38
E-HCAD-25yes53.26
E-CURD-119yes47.31
E-GEOD-84465yes12.56
E-ANND-3yes4.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, CREB1, IRX1, SP1, SP3

miRNA regulators (miRDB)

144 targeting UGT8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-8485100.0077.574731
HSA-MIR-5692A100.0074.406850
HSA-MIR-3646100.0073.565283
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-4262100.0073.263931
HSA-MIR-3163100.0077.238605
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-574-5P100.0066.01989
HSA-MIR-196A-1-3P99.9972.152772
HSA-MIR-366299.9973.825684
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-181A-5P99.9972.962995
HSA-MIR-181B-5P99.9972.972996
HSA-MIR-181C-5P99.9972.952996
HSA-MIR-181D-5P99.9973.042997
HSA-MIR-513B-5P99.9969.962150
HSA-MIR-548N99.9871.944170
HSA-MIR-485-3P99.9870.681585
HSA-MIR-539-3P99.9870.741616
HSA-MIR-1213699.9872.815713
HSA-MIR-4482-3P99.9872.503147
HSA-MIR-3065-5P99.9771.563281
HSA-MIR-302C-5P99.9772.563642
HSA-MIR-1250-3P99.9670.044038
HSA-MIR-570-3P99.9672.414910
HSA-MIR-493-5P99.9672.472382
HSA-MIR-365899.9673.874379
HSA-MIR-302E99.9670.742669
HSA-MIR-548AB99.9571.313488
HSA-MIR-55999.9572.283609

Literature-anchored findings (GeneRIF, showing 14)

  • Single-nucleotide polymorphisms (SNPs) were found in UGT8 gene (PMID:12376738)
  • the GC-box and CRE function cooperatively, and that the CRE regulates the cell-specific expression of the hCGT gene (PMID:15229398)
  • We postulate that molecular link between defective GALT enzyme, which result in classic galactosemia and the cerebroside galactosyl transferase, responsible for galactosylation of cerebrosides, is dependent on concentrations of UDP-galactose. (PMID:16125333)
  • Gene expression of galactosyl ceramide synthase associated with poor pathohistological grading in breast cancer (PMID:19125296)
  • UGT8 is a significant index of tumour aggressiveness and is seen in lung metastases of breast cancer. (PMID:20648017)
  • Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population. (PMID:23118445)
  • High expression of UGT8 accompanied by accumulation of GalCer in MDA-MB-231 cells is associated with a much higher proliferative index and a lower number of apoptotic cells in comparison to the MDA/LUC-shUGT8 cells. (PMID:24391908)
  • Our study suggests that CGT expression is controlled by balanced expression of the negative modulator OLIG2 and positive regulator Nkx2.2, providing new insights into how expression of GalCer is tightly regulated in cell-type- and stage-specific manners. (PMID:24821492)
  • A new role was identified for UGT8 as a modulator of bile acid homeostasis. (PMID:25519837)
  • Data indicate that ceramide galactosyltransferase (UGT8), although enhanced in non-small cell lung carcinoma (NSCLC) tissues, does not meet the criteria of a lung tumor marker. (PMID:27620310)
  • An increase in the immunolabelling of ceramide was observed in cells where UDP glycosyltransferase 8 (UGT8) was down-regulated as opposed to cells where UGT8 was either not regulated or was up-regulated. (PMID:28746357)
  • UGT8 is a potential prognostic indicator and druggable target of basal-like breast cancer. (PMID:29728441)
  • High FA2H and UGT8 transcript levels predict hydroxylated hexosylceramide accumulation in lung adenocarcinoma (PMID:31409741)
  • SOX9-mediated UGT8 expression promotes glycolysis and maintains the malignancy of non-small cell lung cancer. (PMID:34872002)

Cross-species orthologs

88 orthologs

OrganismSymbolGene ID
danio_reriougt8ENSDARG00000037455
mus_musculusUgt8aENSMUSG00000032854
rattus_norvegicusUgt8ENSRNOG00000009345
drosophila_melanogasterUgt36A1FBGN0015663
drosophila_melanogasterUgt35B1FBGN0026314
drosophila_melanogasterUgt35A1FBGN0026315
drosophila_melanogasterUgt37C1FBGN0026754
drosophila_melanogasterUgt37B1FBGN0026755
drosophila_melanogasterUgt37A1FBGN0026756
drosophila_melanogasterUgt36E1FBGN0027070
drosophila_melanogasterUgt49B1FBGN0027073
drosophila_melanogasterUgt36F1FBGN0027074
drosophila_melanogasterUgt307A1FBGN0031887
drosophila_melanogasterUgt36D1FBGN0032713
drosophila_melanogasterUgt49C1FBGN0034605
drosophila_melanogasterUgt316A1FBGN0036842
drosophila_melanogasterUgt37A2FBGN0038082
drosophila_melanogasterUgt37A3FBGN0038083
drosophila_melanogasterUgt49B2FBGN0038886
drosophila_melanogasterUgt303B3FBGN0039085
drosophila_melanogasterUgt303B1FBGN0039086
drosophila_melanogasterUgt303B2FBGN0039087
drosophila_melanogasterUgt304A1FBGN0040250
drosophila_melanogasterUgt302K1FBGN0040251
drosophila_melanogasterUgt303A1FBGN0040252
drosophila_melanogasterUgt35E1FBGN0040253
drosophila_melanogasterUgt35E2FBGN0040255
drosophila_melanogasterUgt302E1FBGN0040257
drosophila_melanogasterUgt302C1FBGN0040259
drosophila_melanogasterUgt37D1FBGN0040260
drosophila_melanogasterUgt37E1FBGN0040261
drosophila_melanogasterUgt37C2FBGN0040262
drosophila_melanogasterUgt305A1FBGN0042179
drosophila_melanogasterUgt35D1FBGN0051002
caenorhabditis_elegansWBGENE00007072
caenorhabditis_elegansWBGENE00007073
caenorhabditis_elegansWBGENE00007402
caenorhabditis_elegansWBGENE00007422
caenorhabditis_elegansWBGENE00007455
caenorhabditis_elegansWBGENE00007885
caenorhabditis_elegansWBGENE00007946
caenorhabditis_elegansWBGENE00008097
caenorhabditis_elegansWBGENE00008486
caenorhabditis_elegansWBGENE00009255
caenorhabditis_elegansWBGENE00010904
caenorhabditis_elegansWBGENE00011006
caenorhabditis_elegansWBGENE00011340
caenorhabditis_elegansWBGENE00011452
caenorhabditis_elegansWBGENE00011453
caenorhabditis_elegansWBGENE00012788
caenorhabditis_elegansWBGENE00013900
caenorhabditis_elegansWBGENE00013905
caenorhabditis_elegansWBGENE00013906
caenorhabditis_elegansWBGENE00015141
caenorhabditis_elegansWBGENE00015369
caenorhabditis_elegansWBGENE00015371
caenorhabditis_elegansWBGENE00015449
caenorhabditis_elegansWBGENE00015577
caenorhabditis_elegansugt-28WBGENE00015693
caenorhabditis_elegansugt-27WBGENE00015694
caenorhabditis_elegansugt-26WBGENE00015695
caenorhabditis_elegansWBGENE00015739
caenorhabditis_elegansWBGENE00015965
caenorhabditis_elegansWBGENE00016013
caenorhabditis_elegansWBGENE00017315
caenorhabditis_elegansWBGENE00017329
caenorhabditis_elegansWBGENE00017331
caenorhabditis_elegansWBGENE00017332
caenorhabditis_elegansWBGENE00017333
caenorhabditis_elegansWBGENE00017334
caenorhabditis_elegansWBGENE00017336
caenorhabditis_elegansWBGENE00017959
caenorhabditis_elegansWBGENE00018206
caenorhabditis_elegansWBGENE00018543
caenorhabditis_elegansWBGENE00018931
caenorhabditis_elegansWBGENE00019232
caenorhabditis_elegansWBGENE00019233
caenorhabditis_elegansWBGENE00019234
caenorhabditis_elegansWBGENE00019235
caenorhabditis_elegansWBGENE00019515
caenorhabditis_elegansWBGENE00019516
caenorhabditis_elegansWBGENE00020587
caenorhabditis_elegansWBGENE00020592
caenorhabditis_elegansWBGENE00020593
caenorhabditis_elegansWBGENE00020594
caenorhabditis_elegansWBGENE00021709
caenorhabditis_elegansWBGENE00044282
caenorhabditis_elegansWBGENE00044286

Paralogs (21): UGT2B10 (ENSG00000109181), UGT2A3 (ENSG00000135220), UGT2B28 (ENSG00000135226), UGT3A1 (ENSG00000145626), UGT2B4 (ENSG00000156096), UGT1A6 (ENSG00000167165), UGT3A2 (ENSG00000168671), UGT2B7 (ENSG00000171234), UGT2A1 (ENSG00000173610), UGT2B15 (ENSG00000196620), UGT2B17 (ENSG00000197888), UGT2B11 (ENSG00000213759), UGT1A9 (ENSG00000241119), UGT1A1 (ENSG00000241635), UGT1A8 (ENSG00000242366), UGT1A10 (ENSG00000242515), UGT1A7 (ENSG00000244122), UGT1A4 (ENSG00000244474), UGT2A2 (ENSG00000271271), UGT1A3 (ENSG00000288702), UGT1A5 (ENSG00000288705)

Protein

Protein identifiers

2-hydroxyacylsphingosine 1-beta-galactosyltransferase — Q16880 (reviewed: Q16880)

Alternative names: Ceramide UDP-galactosyltransferase, Cerebroside synthase, UDP-galactose-ceramide galactosyltransferase

All UniProt accessions (2): D6RFW2, Q16880

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central nervous system and peripheral nervous system. Galactosylates both hydroxy- and non-hydroxy fatty acid-containing ceramides and diglycerides.

Subcellular location. Membrane. Endoplasmic reticulum.

Pathway. Sphingolipid metabolism; galactosylceramide biosynthesis.

Similarity. Belongs to the UDP-glycosyltransferase family.

RefSeq proteins (5): NP_001121646, NP_001309041, NP_001309042, NP_001309043, NP_003351 (=MANE)

Domains & families (InterPro)

IDNameType
IPR002213UDP_glucos_transFamily
IPR035595UDP_glycos_trans_CSConserved_site
IPR050271UDP-glycosyltransferaseFamily

Pfam: PF00201

Enzyme classification (BRENDA):

  • EC 2.4.1.47 — N-acylsphingosine galactosyltransferase (BRENDA: 9 organisms, 29 substrates, 13 inhibitors, 5 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
2-(2-HYDROXYACYL)SPHINGOSINE0.018–0.153
UDPGALACTOSE0.041

Catalyzed reactions (Rhea), 4 shown:

  • an N-acylsphing-4-enine + UDP-alpha-D-galactose = a beta-D-galactosyl-(1<->1’)-N-acylsphing-4-enine + UDP + H(+) (RHEA:13093)
  • N-(2-hydroxy-hexanoyl)-sphing-4-enine + UDP-alpha-D-galactose = N-(2-hydroxy-hexanoyl)-beta-D-galactosyl-sphing-4-enine + UDP + H(+) (RHEA:43400)
  • N-(2-hydroxy-hexanoyl)-sphinganine + UDP-alpha-D-galactose = N-(2-hydroxyhexanoyl)-beta-D-galactosylsphinganine + UDP + H(+) (RHEA:43404)
  • an N-acyl-sphingoid base + UDP-alpha-D-galactose = a D-galactosylceramide + UDP + H(+) (RHEA:48344)

UniProt features (12 total): sequence conflict 4, glycosylation site 3, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q16880-F189.750.78

Functional residue map

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

Glycosylation sites (3): 78, 333, 442

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-9840309Glycosphingolipid biosynthesis

MSigDB gene sets: 241 (showing top): GOBP_RESPONSE_TO_IMMOBILIZATION_STRESS, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_NEUROGENESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, KRASNOSELSKAYA_ILF3_TARGETS_DN, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ENSHEATHMENT_OF_NEURONS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (13): protein localization to paranode region of axon (GO:0002175), galactosylceramide biosynthetic process (GO:0006682), glycosphingolipid biosynthetic process (GO:0006688), cytoskeleton organization (GO:0007010), central nervous system development (GO:0007417), peripheral nervous system development (GO:0007422), paranodal junction assembly (GO:0030913), response to immobilization stress (GO:0035902), neuron projection morphogenesis (GO:0048812), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), nervous system development (GO:0007399), glycolipid biosynthetic process (GO:0009247)

GO Molecular Function (6): N-acylsphingosine galactosyltransferase activity (GO:0003851), UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity (GO:0008489), UDP-glycosyltransferase activity (GO:0008194), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), lumenal side of endoplasmic reticulum membrane (GO:0098553), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Glycosphingolipid metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
system development3
nervous system development2
UDP-galactosyltransferase activity2
glycosyltransferase activity2
protein localization to axon1
galactosylceramide metabolic process1
glycosphingolipid biosynthetic process1
galactolipid biosynthetic process1
ceramide biosynthetic process1
glycosphingolipid metabolic process1
glycolipid biosynthetic process1
sphingolipid biosynthetic process1
organelle organization1
cell-cell junction assembly1
cellular component assembly involved in morphogenesis1
myelin assembly1
response to stress1
neuron projection development1
plasma membrane bounded cell projection morphogenesis1
primary metabolic process1
lipid metabolic process1
glycolipid metabolic process1
lipid biosynthetic process1
carbohydrate derivative biosynthetic process1
catalytic activity1
transferase activity1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
endoplasmic reticulum membrane1
lumenal side of membrane1
cellular anatomical structure1

Protein interactions and networks

STRING

1142 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
UGT8SLC35A2P78381756
UGT8UGCGQ16739700
UGT8GALCP54803694
UGT8GAL3ST1Q99999647
UGT8FA2HQ7L5A8597
UGT8MAGP20916541
UGT8CERKQ8TCT0532
UGT8B4GALT6Q9UBX8530
UGT8UNC5CO95185524
UGT8MBPP02686520
UGT8ARSAP15289507
UGT8SPTLC2O15270499
UGT8CERS2Q96G23479
UGT8SPTLC1O15269477
UGT8SPTLC3Q9NUV7475

IntAct

112 interactions, top by confidence:

ABTypeScore
TRDNTMEM223psi-mi:“MI:0914”(association)0.640
FBXO6MAN2B1psi-mi:“MI:0914”(association)0.640
DDX3Xpsi-mi:“MI:0914”(association)0.630
CANXPGRMC1psi-mi:“MI:0914”(association)0.570
FUT1GOLIM4psi-mi:“MI:0914”(association)0.530
HMOX2PRAF2psi-mi:“MI:0914”(association)0.530
FBXO2TMEM131Lpsi-mi:“MI:0914”(association)0.530
CLGNNPC1psi-mi:“MI:0914”(association)0.530
NCEH1CLGNpsi-mi:“MI:0914”(association)0.530
C1orf54EXTL3psi-mi:“MI:0914”(association)0.530
CHRNA4FZD6psi-mi:“MI:0914”(association)0.530
LPAR1TMEM223psi-mi:“MI:0914”(association)0.530
UGT8H1-0psi-mi:“MI:0915”(physical association)0.400
UGT8ADRA1Apsi-mi:“MI:0915”(physical association)0.370
UGT8AGTR1psi-mi:“MI:0915”(physical association)0.370
NEK4E2F8psi-mi:“MI:0914”(association)0.350
UPK1ATMEM223psi-mi:“MI:0914”(association)0.350
SCGB2A2GXYLT2psi-mi:“MI:0914”(association)0.350
SEC22BNBASpsi-mi:“MI:0914”(association)0.350
CSGALNACT2CLASP2psi-mi:“MI:0914”(association)0.350
ADPGKTOR1Bpsi-mi:“MI:0914”(association)0.350
MPPE1ADAM10psi-mi:“MI:0914”(association)0.350
PTCH1PLXNB2psi-mi:“MI:0914”(association)0.350

BioGRID (128): UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Proximity Label-MS), UGT8 (Proximity Label-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), UGT8 (Affinity Capture-MS)

ESM2 similar proteins: A0A291PQF1, A0A291PQG3, A0A291PQH4, A8WLF6, O16881, O19103, O75310, P08541, P08542, P09875, P16662, P17717, P18569, P19488, P34317, P36511, P36513, P36537, Q09426, Q10941, Q10944, Q16880, Q18081, Q1LZI1, Q20086, Q21706, Q22180, Q22181, Q22295, Q25489, Q27757, Q3SY77, Q3UP75, Q5RFJ3, Q62789, Q63ZR6, Q64676, Q6K1J1, Q6NUS8, Q6PDD0

Diamond homologs: A0A096SRM5, A0A0B6VIJ5, A0A0D1CFF0, A0A0M4KE44, A0A193AU77, A0A1L7U2E9, A0A224AKZ9, A0A224AM54, A0A291PQF1, A0A291PQG3, A0A291PQH4, A0A2Z5CV93, A5U6W6, B4G072, C3W7B0, G2WW48, K7NBW3, O02663, O19103, O23401, O31853, O60656, O75310, O75795, O77649, O82385, O97951, P06133, P08430, P08541, P08542, P09875, P0DTE4, P0DTE5, P16662, P17717, P19224, P19488, P20720, P22309

SIGNOR signaling

1 interactions.

AEffectBMechanism
IRX1“up-regulates quantity by expression”UGT8“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 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:

PathwayPartnersFoldFDR
ER-Phagosome pathway68.7×9e-03
Interferon gamma signaling68.4×9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance46
Likely benign9
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1628 predictions. Top by Δscore:

VariantEffectΔscore
4:114622876:CAGC:Cacceptor_loss1.0000
4:114622877:A:AGacceptor_gain1.0000
4:114622878:G:GGacceptor_gain1.0000
4:114622878:GCT:Gacceptor_gain1.0000
4:114622878:GCTAT:Gacceptor_gain1.0000
4:114623700:GAA:Gdonor_gain1.0000
4:114623703:G:GGdonor_gain1.0000
4:114663992:CA:Cacceptor_loss1.0000
4:114663993:A:AGacceptor_gain1.0000
4:114663993:A:Gacceptor_loss1.0000
4:114663993:AG:Aacceptor_gain1.0000
4:114663994:G:GAacceptor_gain1.0000
4:114663994:GG:Gacceptor_gain1.0000
4:114663994:GGA:Gacceptor_gain1.0000
4:114663994:GGAT:Gacceptor_gain1.0000
4:114664051:T:TAacceptor_gain1.0000
4:114664137:GGTAA:Gdonor_loss1.0000
4:114664138:G:GGdonor_gain1.0000
4:114664138:GTAA:Gdonor_loss1.0000
4:114665752:GCTTG:Gdonor_gain1.0000
4:114665753:CTTGG:Cdonor_loss1.0000
4:114665754:TTGGT:Tdonor_loss1.0000
4:114665757:GTAA:Gdonor_loss1.0000
4:114665758:T:Gdonor_loss1.0000
4:114665759:AAG:Adonor_loss1.0000
4:114668080:TTCA:Tacceptor_loss1.0000
4:114668082:CAG:Cacceptor_loss1.0000
4:114668083:A:AGacceptor_gain1.0000
4:114668083:AG:Aacceptor_gain1.0000
4:114668084:G:GCacceptor_loss1.0000

AlphaMissense

3557 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:114622977:A:CS33R0.997
4:114622979:C:AS33R0.997
4:114622979:C:GS33R0.997
4:114623221:G:AC114Y0.997
4:114623222:T:GC114W0.997
4:114623281:T:CL134P0.997
4:114668111:A:CS357R0.997
4:114668113:C:AS357R0.997
4:114668113:C:GS357R0.997
4:114668129:A:CS363R0.997
4:114668131:T:AS363R0.997
4:114668131:T:GS363R0.997
4:114668187:A:CD382A0.997
4:114668187:A:GD382G0.997
4:114668187:A:TD382V0.997
4:114668228:G:TG396W0.997
4:114664053:G:AG294E0.996
4:114664133:T:AW321R0.996
4:114664133:T:CW321R0.996
4:114622971:T:CF31L0.995
4:114622973:T:AF31L0.995
4:114622973:T:GF31L0.995
4:114623220:T:AC114S0.995
4:114623220:T:CC114R0.995
4:114623221:G:CC114S0.995
4:114623293:A:GD138G0.995
4:114623307:T:CC143R0.995
4:114623367:T:AW163R0.995
4:114623367:T:CW163R0.995
4:114623468:T:AN196K0.995

dbSNP variants (sampled 300 via entrez): RS1000072902 (4:114601951 C>A), RS10001078 (4:114612619 G>A), RS1000111648 (4:114653701 C>G,T), RS1000143718 (4:114660547 T>A), RS1000217455 (4:114640251 C>T), RS1000283139 (4:114635566 T>A), RS1000290986 (4:114604634 T>C), RS10002942 (4:114639465 T>C,G), RS1000302931 (4:114626903 A>G), RS1000315753 (4:114672857 T>C), RS1000331345 (4:114629746 A>T), RS10003335 (4:114635869 A>G), RS1000339867 (4:114655185 T>C,G), RS1000398536 (4:114666042 A>G), RS1000414235 (4:114672629 C>A,T)

Disease associations

OMIM: gene MIM:601291 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

StudyTraitp-value
GCST004076_19Optic disc area4.000000e-07
GCST004076_4Optic disc area2.000000e-08
GCST004615_20Hemoglobin concentration1.000000e-09
GCST008058_251Estimated glomerular filtration rate4.000000e-13
GCST008059_37Estimated glomerular filtration rate3.000000e-14
GCST008157_35Body fat mass1.000000e-07
GCST009391_553Metabolite levels4.000000e-07
GCST010083_134Hemoglobin levels3.000000e-09
GCST010083_212Hemoglobin levels1.000000e-09
GCST90002383_397Hematocrit2.000000e-12
GCST90002384_143Hemoglobin1.000000e-12
GCST90002403_433Red blood cell count1.000000e-15

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0004509hemoglobin measurement
EFO:0009769histidine measurement
EFO:0004348hematocrit
EFO:0004305erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4739855 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs34115976MIR577, UGT80.000

ChEMBL bioactivities

38 potent at pChembl≥5 of 38 total, top 36 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.70IC500.2nMCHEMBL4785914
9.40IC500.4nMCHEMBL4796521
9.40IC500.4nMCHEMBL4787939
9.22IC500.6nMCHEMBL4796521
9.05IC500.9nMCHEMBL4787939
9.05IC500.9nMCHEMBL4750073
9.00IC501nMCHEMBL4776963
8.96IC501.1nMCHEMBL4750073
8.77IC501.7nMCHEMBL4750432
8.70IC502nMCHEMBL4765010
8.54IC502.9nMCHEMBL4750432
8.52IC503nMCHEMBL4776963
7.75IC5018nMCHEMBL4755797
7.43IC5037nMCHEMBL4755797
7.37IC5043nMCHEMBL4757982
7.32IC5048nMCHEMBL4757982
7.17IC5067nMCHEMBL4760937
7.05IC5090nMCHEMBL4760937
7.01IC5097nMCHEMBL4795937
6.92IC50120nMCHEMBL4795937
6.77IC50170nMCHEMBL4799472
6.72IC50190nMCHEMBL4797076
6.70IC50200nMCHEMBL4764180
6.70IC50200nMCHEMBL4751927
6.50IC50320nMCHEMBL4747085
6.48IC50330nMCHEMBL4751927
6.46IC50350nMCHEMBL4797076
6.44IC50360nMCHEMBL4799472
6.35IC50450nMCHEMBL4745037
6.29IC50510nMCHEMBL4799203
6.21IC50610nMCHEMBL4791074
6.21IC50610nMCHEMBL4762406
6.19IC50640nMCHEMBL4747085
6.18IC50660nMCHEMBL4745037
6.01IC50980nMCHEMBL4752928
5.85IC501400nMCHEMBL4791074

PubChem BioAssay actives

38 with measured affinity, of 38 total; 21 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-[(2S)-1-(trifluoromethoxy)propan-2-yl]carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0002uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-[(2S)-butan-2-yl]carbamate1725549: Inhibition of UGT8 in human OE19 cells assessed as redcution in GalCer accumulation measured after 72 hrs by LC-MS/MS analysisic500.0004uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-[2-(trifluoromethoxy)ethyl]carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0004uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-[(1S)-1-cyclopropylethyl]carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0009uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-(cyclopropylmethyl)carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0010uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] 3-(trifluoromethoxy)azetidine-1-carboxylate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0017uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-propan-2-ylcarbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0020uM
cyclopropylmethyl N-[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl]carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0180uM
cyclopropylmethyl N-[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]azetidin-3-yl]carbamate1725549: Inhibition of UGT8 in human OE19 cells assessed as redcution in GalCer accumulation measured after 72 hrs by LC-MS/MS analysisic500.0430uM
N-methyl-5-[4-[2-oxo-2-(propan-2-ylamino)ethyl]piperazin-1-yl]-7-(trifluoromethyl)thieno[3,2-b]pyridine-3-carboxamide1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0670uM
2-[4-[3-propanoyl-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperazin-1-yl]-N-propan-2-ylacetamide1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.0970uM
5-[4-[1-(cyclopropylamino)-1-oxopropan-2-yl]piperazin-1-yl]-N-methyl-7-(trifluoromethyl)thieno[3,2-b]pyridine-3-carboxamide1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.1700uM
5-[4-[2-hydroxy-3-[(2-methylpropan-2-yl)oxy]propyl]piperazin-1-yl]-N-methyl-7-(trifluoromethyl)thieno[3,2-b]pyridine-3-carboxamide1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.1900uM
N-methyl-5-[4-(2-propan-2-yloxyethyl)piperazin-1-yl]-7-(trifluoromethyl)thieno[3,2-b]pyridine-3-carboxamide1725549: Inhibition of UGT8 in human OE19 cells assessed as redcution in GalCer accumulation measured after 72 hrs by LC-MS/MS analysisic500.2000uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]azetidin-3-yl] N-(cyclopropylmethyl)carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.2000uM
2-[4-[3-(azetidine-1-carbonyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperazin-1-yl]-N-propan-2-ylacetamide1725549: Inhibition of UGT8 in human OE19 cells assessed as redcution in GalCer accumulation measured after 72 hrs by LC-MS/MS analysisic500.3200uM
N-methyl-5-[4-(2-propan-2-yloxyacetyl)piperazin-1-yl]-7-(trifluoromethyl)thieno[3,2-b]pyridine-3-carboxamide1725549: Inhibition of UGT8 in human OE19 cells assessed as redcution in GalCer accumulation measured after 72 hrs by LC-MS/MS analysisic500.4500uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] N-(2-pyrrolidin-1-ylethyl)carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.5100uM
5-[4-(3,3-dimethyl-2-oxobutyl)piperazin-1-yl]-N-methyl-7-(trifluoromethyl)thieno[3,2-b]pyridine-3-carboxamide1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.6100uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]pyrrolidin-3-yl] N-(cyclopropylmethyl)carbamate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.6100uM
[1-[3-(methylcarbamoyl)-7-(trifluoromethyl)thieno[3,2-b]pyridin-5-yl]piperidin-4-yl] 3-[(dimethylamino)methyl]azetidine-1-carboxylate1725548: Inhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisic500.9800uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, affects expression8
methylmercuric chloridedecreases expression, increases expression3
trichostatin Aaffects cotreatment, increases expression3
sodium arseniteincreases expression, decreases expression2
entinostatincreases expression, affects cotreatment2
belinostatincreases expression, affects cotreatment2
Panobinostataffects cotreatment, increases expression2
aristolochic acid Idecreases expression1
arsenitedecreases expression1
butyraldehydeincreases expression1
potassium chromate(VI)increases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
abrinedecreases expression1
mirdametinibaffects cotreatment, decreases expression1
dorsomorphinaffects cotreatment, increases expression1
jinfukangdecreases expression1
(+)-JQ1 compoundaffects cotreatment, decreases expression1
Sunitinibdecreases expression1
Zoledronic Aciddecreases expression1
Vorinostatincreases expression, affects cotreatment1
Acetaminophenincreases expression1
Benzo(a)pyreneincreases methylation1
Cadmiumdecreases expression1
Carmustineincreases expression1
Cisplatindecreases expression1
Environmental Pollutantsaffects expression1
Fluorouracilaffects reaction, decreases expression1
Hydrogen Peroxideincreases expression1
Nickeldecreases expression1
Thimerosaldecreases expression1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4731219BindingInhibition of UGT8 in human OE19 cells assessed as redcution in SFT accumulation measured after 72 hrs by LC-MS/MS analysisBrain Penetrable Inhibitors of Ceramide Galactosyltransferase for the Treatment of Lysosomal Storage Disorders. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 78

This page pulls from 78 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot