B4GALT4

Summary

B4GALT4 (beta-1,4-galactosyltransferase 4, HGNC:927) is a protein-coding gene on chromosome 3q13.32, encoding Beta-1,4-galactosyltransferase 4 (O60513). Galactose (Gal) transferase involved in the synthesis of terminal N-acetyllactosamine (LacNac) unit present on glycan chains of glycoproteins and glycosphingolipids.

This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. The enzyme encoded by this gene appears to mainly play a role in glycolipid biosynthesis. Two alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 8702 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_003778

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:927
Approved symbol	B4GALT4
Name	beta-1,4-galactosyltransferase 4
Location	3q13.32
Locus type	gene with protein product
Status	Approved
Aliases	beta4Gal-T4
Ensembl gene	ENSG00000121578
Ensembl biotype	protein_coding
OMIM	604015
Entrez	8702

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 48 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000359213, ENST00000393765, ENST00000459778, ENST00000459820, ENST00000460321, ENST00000460395, ENST00000467604, ENST00000470111, ENST00000471675, ENST00000472471, ENST00000473887, ENST00000475803, ENST00000479150, ENST00000479308, ENST00000480814, ENST00000483209, ENST00000484595, ENST00000487579, ENST00000491906, ENST00000493932, ENST00000906939, ENST00000906940, ENST00000906941, ENST00000906942, ENST00000906943, ENST00000906944, ENST00000906945, ENST00000906946, ENST00000906947, ENST00000906948, ENST00000906949, ENST00000906950, ENST00000906951, ENST00000906952, ENST00000906953, ENST00000912592, ENST00000912593, ENST00000912594, ENST00000952669, ENST00000952670, ENST00000952671, ENST00000952672, ENST00000952673, ENST00000952674, ENST00000952675, ENST00000952676, ENST00000952677, ENST00000952678, ENST00000952679, ENST00000952680, ENST00000952681, ENST00000952682, ENST00000952683, ENST00000952684, ENST00000952685

RefSeq mRNA: 2 — MANE Select: NM_003778 NM_003778, NM_212543

CCDS: CCDS2986

Canonical transcript exons

ENST00000393765 — 8 exons

Exon	Start	End
ENSE00000823597	119218650	119218772
ENSE00001012113	119236853	119237070
ENSE00001012114	119229847	119230244
ENSE00001829592	119240850	119240878
ENSE00001908362	119211742	119212681
ENSE00003524544	119226809	119227041
ENSE00003526261	119216240	119216344
ENSE00003685181	119224058	119224245

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.2723 / max 348.3202, expressed in 1783 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43972	8.5578	1693
43973	5.7145	1697

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.77	gold quality
type B pancreatic cell	CL:0000169	96.31	silver quality
olfactory bulb	UBERON:0002264	95.99	silver quality
nasal cavity epithelium	UBERON:0005384	94.19	gold quality
amniotic fluid	UBERON:0000173	94.12	gold quality
epithelium of nasopharynx	UBERON:0001951	93.79	gold quality
gall bladder	UBERON:0002110	93.76	gold quality
rectum	UBERON:0001052	93.07	gold quality
islet of Langerhans	UBERON:0000006	92.71	gold quality
oocyte	CL:0000023	92.49	gold quality
epithelial cell of pancreas	CL:0000083	92.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.12	gold quality
secondary oocyte	CL:0000655	92.05	gold quality
nasal cavity mucosa	UBERON:0001826	92.04	gold quality
lower esophagus mucosa	UBERON:0035834	92.02	gold quality
stromal cell of endometrium	CL:0002255	91.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.88	gold quality
mucosa of transverse colon	UBERON:0004991	91.56	gold quality
corpus epididymis	UBERON:0004359	91.52	gold quality
buccal mucosa cell	CL:0002336	91.28	gold quality
palpebral conjunctiva	UBERON:0001812	90.88	gold quality
endometrium	UBERON:0001295	90.61	gold quality
medial globus pallidus	UBERON:0002477	90.14	gold quality
esophagus squamous epithelium	UBERON:0006920	90.07	gold quality
parotid gland	UBERON:0001831	89.84	gold quality
tibia	UBERON:0000979	89.80	gold quality
tendon	UBERON:0000043	89.78	gold quality
jejunal mucosa	UBERON:0000399	89.59	gold quality
tongue squamous epithelium	UBERON:0006919	89.51	gold quality
trachea	UBERON:0003126	89.47	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	13.92
E-MTAB-8271	yes	6.43
E-ANND-3	yes	5.51
E-GEOD-124858	no	207.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting B4GALT4, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-LET-7G-3P	99.85	70.43	1929

Literature-anchored findings (GeneRIF, showing 3)

• expression of the beta4GalT4 gene is controlled by Sp1, and Sp1 plays a key role in the activation of the beta4GalT4 gene in colon cancer cells. (PMID:28228616)
• N-glycosylation of the human beta1,4-galactosyltransferase 4 is crucial for its activity and Golgi localization. (PMID:32827291)
• The critical role of B4GALT4 in promoting microtubule spindle assembly in HCC through the regulation of PLK1 and RHAMM expression. (PMID:34270095)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	b4galt4	ENSDARG00000104042
mus_musculus	B4galt4	ENSMUSG00000022793
rattus_norvegicus	B4galt4	ENSRNOG00000003114
drosophila_melanogaster	beta4GalNAcTA	FBGN0027538
caenorhabditis_elegans	bre-4	WBGENE00000269

Paralogs (6): B4GALT7 (ENSG00000027847), B4GALT1 (ENSG00000086062), B4GALT2 (ENSG00000117411), B4GALT6 (ENSG00000118276), B4GALT5 (ENSG00000158470), B4GALT3 (ENSG00000158850)

Protein

Protein identifiers

Beta-1,4-galactosyltransferase 4 — O60513 (reviewed: O60513)

Alternative names: Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase, Lactotriaosylceramide beta-1,4-galactosyltransferase, N-acetyllactosamine synthase, Nal synthase, UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 4, UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 4

All UniProt accessions (11): B2RAZ5, C9J3R8, C9J4S5, C9J5S0, C9J644, C9JA31, C9JE00, C9JY35, C9JY38, E7ETS9, O60513

UniProt curated annotations — full annotation on UniProt →

Function. Galactose (Gal) transferase involved in the synthesis of terminal N-acetyllactosamine (LacNac) unit present on glycan chains of glycoproteins and glycosphingolipids. Catalyzes the transfer of Gal residue via a beta1->4 linkage from UDP-Gal to the non-reducing terminal N-acetyl glucosamine 6-O-sulfate (6-O-sulfoGlcNAc) in the linearly growing chain of both N- and O-linked keratan sulfate proteoglycans. Cooperates with B3GNT7 N-acetyl glucosamine transferase and CHST6 and CHST1 sulfotransferases to construct and elongate mono- and disulfated disaccharide units [->3Galbeta1->4(6-sulfoGlcNAcbeta)1->] and [->3(6-sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Transfers Gal residue via a beta1->4 linkage to terminal 6-O-sulfoGlcNAc within the LacNac unit of core 2 O-glycans forming 6-sulfo-sialyl-Lewis X (sLex). May contribute to the generation of sLex epitope on mucin-type glycoproteins that serve as ligands for SELL/L-selectin, a major regulator of leukocyte migration. In the biosynthesis pathway of neolacto-series glycosphingolipids, transfers Gal residue via a beta1->4 linkage to terminal GlcNAc of a lactotriaosylceramide (Lc3Cer) acceptor to form a neolactotetraosylceramide. Efficiently galactosylates both non-sulfated and 6-O-sulfated terminal GlcNAc moities on G0 complex-type N-glycans.

Subunit / interactions. Interacts with SLC35A2 (isoform 2; UGT1).

Subcellular location. Golgi apparatus membrane. Secreted.

Tissue specificity. Highest expression is observed in placenta, pancreas, kidney and heart. Expressed in corneal epithelial cells.

Post-translational modifications. N-glycosylated.

Activity regulation. Up-regulated by LALBA.

Pathway. Protein modification; protein glycosylation. Glycolipid biosynthesis.

Similarity. Belongs to the glycosyltransferase 7 family.

RefSeq proteins (2): NP_003769, NP_997708 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003859	Galactosyl_T	Family
IPR027791	Galactosyl_T_C	Domain
IPR027995	Galactosyl_T_N	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF02709, PF13733

Enzyme classification (BRENDA):

• EC 2.4.1.275 — neolactotriaosylceramide beta-1,4-galactosyltransferase (BRENDA: 3 organisms, 18 substrates, 2 inhibitors, 4 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GALACTOSE	0.105–0.25	2
4-NITROPHENYL N-ACETYL-1-THIO-BETA-D-GLUCOSAMINI	0.238	1
N-ACETYL-BETA-D-GALACTOSAMINOPYRANOSYL-(1->3)-BE	0.11	1

Catalyzed reactions (Rhea), 5 shown:

• N-acetyl-D-glucosamine + UDP-alpha-D-galactose = beta-D-galactosyl-(1->4)-N-acetyl-D-glucosamine + UDP + H(+) (RHEA:17745)
• a beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + UDP-alpha-D-galactose = a neolactoside nLc4Cer(d18:1(4E)) + UDP + H(+) (RHEA:31499)
• 3-O-{beta-D-galactosyl-(1->3)-[6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + UDP-alpha-D-galactose = 3-O-{beta-D-galactosyl-(1->3)-[beta-D-galactosyl-(1->4)-6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + UDP + H(+) (RHEA:67872)
• 3-O-{beta-D-galactosyl-(1->3)-[6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + UDP-alpha-D-galactose = 3-O-{beta-D-galactosyl-(1->3)-[beta-D-galactosyl-(1->4)-6-O-sulfo-N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + UDP + H(+) (RHEA:67948)
• an N(4)-{6-O-sulfo-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L–asparaginyl-[protein] + 2 UDP-alpha-D-galactose = an N(4)-{beta-D-Gal-(1->4)-6-O-sulfo-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + 2 UDP + 2 H(+) (RHEA:84279)

UniProt features (23 total): binding site 10, mutagenesis site 3, topological domain 2, glycosylation site 2, disulfide bond 2, chain 1, sequence variant 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60513-F1	90.78	0.78

Functional residue map

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

Ligand- & substrate-binding residues (10): 258–261; 289–291; 289; 301; 129–133; 168–170; 195–196; 196; 224; 256

Disulfide bonds (2): 77–118, 189–208

Glycosylation sites (2): 220, 335

Mutagenesis-validated functional residues (3):

Position	Phenotype
6	has no impact on n-glycosylation.
222	has no impact on localization to the golgi apparatus. decreases n-glycosylation. impairs the catalytic activity. impairs
337	impairs localization to the golgi apparatus. abolishes n-glycosylation. impairs the interaction with slc35a/ugt1. impair

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2022854	Keratan sulfate biosynthesis
R-HSA-975577	N-Glycan antennae elongation
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638074	Keratan sulfate/keratin metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-597592	Post-translational protein modification
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-975576	N-glycan antennae elongation in the medial/trans-Golgi

MSigDB gene sets: 178 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, MODULE_205, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_GLYCOSPHINGOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

GO Biological Process (7): lactosylceramide biosynthetic process (GO:0001572), carbohydrate metabolic process (GO:0005975), obsolete membrane lipid metabolic process (GO:0006643), keratan sulfate proteoglycan biosynthetic process (GO:0018146), obsolete protein glycosylation (GO:0006486), lipid metabolic process (GO:0006629), obsolete glycosylation (GO:0070085)

GO Molecular Function (8): beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity (GO:0003831), N-acetyllactosamine synthase activity (GO:0003945), galactosyltransferase activity (GO:0008378), UDP-galactosyltransferase activity (GO:0035250), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (6): Golgi membrane (GO:0000139), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), membrane (GO:0016020), endomembrane system (GO:0012505), Golgi cisterna membrane (GO:0032580)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Keratan sulfate/keratin metabolism	1
N-glycan antennae elongation in the medial/trans-Golgi	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Glycosaminoglycan metabolism	1
Post-translational protein modification	1
Metabolism of proteins	1
Metabolism	1
Asparagine N-linked glycosylation	1
Transport to the Golgi and subsequent modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
primary metabolic process	2
UDP-galactosyltransferase activity	2
glycosphingolipid biosynthetic process	1
ceramide biosynthetic process	1
proteoglycan biosynthetic process	1
keratan sulfate proteoglycan metabolic process	1
hexosyltransferase activity	1
UDP-glycosyltransferase activity	1
galactosyltransferase activity	1
cation binding	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1
organelle membrane	1
Golgi cisterna	1

Protein interactions and networks

STRING

702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B4GALT4	B3GNT7	Q8NFL0	628
B4GALT4	C1GALT1	Q9NS00	621
B4GALT4	CHST6	Q9GZX3	606
B4GALT4	B3GNT5	Q9BYG0	565
B4GALT4	MGAT4A	Q9UM21	550
B4GALT4	B3GALT5	Q9Y2C3	545
B4GALT4	B4GALNT2	Q8NHY0	544
B4GALT4	B3GNT2	Q9NY97	544
B4GALT4	B3GALT4	O96024	544
B4GALT4	B3GNT3	Q9Y2A9	530
B4GALT4	ST3GAL6	Q9Y274	508
B4GALT4	CDC40	O60508	491
B4GALT4	B3GALT1	Q9Y5Z6	490
B4GALT4	FUT8	Q9BYC5	486
B4GALT4	MGAT5B	Q3V5L5	483

IntAct

36 interactions, top by confidence:

A	B	Type	Score
B4GALT4	HSPA5	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
Psmb5		psi-mi:“MI:0914”(association)	0.350
Tubg1	ZC3H18	psi-mi:“MI:0914”(association)	0.350
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLDND1	MAN1A2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
B4GALT4	PIPSL	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
CRLF1	MANBA	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
SLURP1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
CLDND1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
CST8	HS3ST1	psi-mi:“MI:0914”(association)	0.350
CGREF1	HS3ST1	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): B4GALT4 (Affinity Capture-RNA), B4GALT4 (Affinity Capture-RNA), B4GALT4 (Affinity Capture-MS), B4GALT4 (Affinity Capture-MS), NGLY1 (Affinity Capture-MS), ITGA6 (Affinity Capture-MS), SP3 (Affinity Capture-MS), B4GALT4 (Affinity Capture-MS), B4GALT4 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), ITGA6 (Affinity Capture-MS), B4GALT4 (Affinity Capture-MS), NGLY1 (Affinity Capture-MS), STRN3 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S6M251, A8Y1P7, H0ZAB5, L7YAI7, O43286, O43505, O60513, O60909, O61394, O61397, O88419, P08037, P15291, P15535, P34548, P34678, P70419, Q09323, Q09363, Q14435, Q3YL68, Q5EA01, Q5EA87, Q5QQ54, Q5QQ55, Q5R4S2, Q66HH1, Q6P768, Q6WV17, Q6WV20, Q7K755, Q80WN7, Q80WN8, Q80WN9, Q8BWP8, Q8I136, Q8IA42, Q8MV48, Q8MVS5, Q91YY2

Diamond homologs: A0A1S6M251, A8Y1P7, O43286, O60512, O60513, O60909, O88419, P08037, P15291, P15535, P34548, Q09323, Q3YL68, Q5EA87, Q5NVN3, Q66HH1, Q6P768, Q80WN7, Q80WN8, Q80WN9, Q8R087, Q91YY2, Q9GUM2, Q9JJ04, Q9JMK0, Q9UBV7, Q9UBX8, Q9VBZ9, Q9WVK5, Q9Z2Y2, Q6ZQ11, Q86X52

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1786 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119216233:GACTT:G	donor_loss	1.0000
3:119216234:ACTTA:A	donor_loss	1.0000
3:119216235:CTTA:C	donor_loss	1.0000
3:119216236:TTACC:T	donor_loss	1.0000
3:119216237:T:TG	donor_loss	1.0000
3:119216238:A:AC	donor_gain	1.0000
3:119216239:C:CC	donor_gain	1.0000
3:119216239:C:CT	donor_loss	1.0000
3:119216239:CCGTT:C	donor_gain	1.0000
3:119216340:CAACC:C	acceptor_gain	1.0000
3:119216342:ACCC:A	acceptor_loss	1.0000
3:119216343:CC:C	acceptor_gain	1.0000
3:119216344:CC:C	acceptor_gain	1.0000
3:119216345:C:CA	acceptor_loss	1.0000
3:119216346:T:G	acceptor_loss	1.0000
3:119224244:GCC:G	acceptor_loss	1.0000
3:119224244:GCCT:G	acceptor_gain	1.0000
3:119224245:CCTA:C	acceptor_loss	1.0000
3:119224246:CTAG:C	acceptor_loss	1.0000
3:119224247:T:G	acceptor_loss	1.0000
3:119226804:CTCA:C	donor_loss	1.0000
3:119226805:TCA:T	donor_loss	1.0000
3:119226806:CACCT:C	donor_loss	1.0000
3:119226807:ACCTG:A	donor_loss	1.0000
3:119229845:A:AC	donor_gain	1.0000
3:119229846:C:CC	donor_gain	1.0000
3:119216341:AACC:A	acceptor_gain	0.9900
3:119216345:C:CC	acceptor_gain	0.9900
3:119216345:C:T	acceptor_gain	0.9900
3:119219676:C:CT	acceptor_gain	0.9900

AlphaMissense

2267 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119218668:T:A	D260V	1.000
3:119218668:T:G	D260A	1.000
3:119218669:C:G	D260H	1.000
3:119218679:C:A	W256C	1.000
3:119218679:C:G	W256C	1.000
3:119218681:A:G	W256R	1.000
3:119218681:A:T	W256R	1.000
3:119218704:C:T	G248E	1.000
3:119216344:C:A	R266S	0.999
3:119216344:C:G	R266S	0.999
3:119218650:C:A	R266M	0.999
3:119218650:C:G	R266T	0.999
3:119218659:A:G	L263P	0.999
3:119218665:T:A	D261V	0.999
3:119218665:T:C	D261G	0.999
3:119218665:T:G	D261A	0.999
3:119218666:C:G	D261H	0.999
3:119218667:G:C	D260E	0.999
3:119218667:G:T	D260E	0.999
3:119218668:T:C	D260G	0.999
3:119218669:C:A	D260Y	0.999
3:119218671:T:A	E259V	0.999
3:119218704:C:A	G248V	0.999
3:119224142:A:G	L197P	0.999
3:119224151:T:A	D194V	0.999
3:119224151:T:G	D194A	0.999
3:119224228:A:C	F168L	0.999
3:119224228:A:T	F168L	0.999
3:119224230:A:G	F168L	0.999
3:119212637:C:T	G316E	0.998

dbSNP variants (sampled 300 via entrez): RS1000132640 (3:119240643 T>C,G), RS1000268480 (3:119225674 C>T), RS1000336401 (3:119232093 G>T), RS1000436768 (3:119238841 A>G), RS1000731267 (3:119227752 C>A,T), RS1000801202 (3:119234516 G>C), RS1001113252 (3:119222180 G>A,C), RS1001315754 (3:119211782 T>C), RS1001320208 (3:119242498 G>A,T), RS1001771399 (3:119240704 C>T), RS1001830202 (3:119227622 C>T), RS1001880726 (3:119227366 C>G,T), RS1001892547 (3:119216823 A>G), RS1002235365 (3:119216479 C>T), RS1002434971 (3:119233772 A>G)

Disease associations

OMIM: gene MIM:604015 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002777_12	Clozapine-induced cytotoxicity	9.000000e-06
GCST004485_2	Survival in pancreatic cancer	6.000000e-06
GCST007643_2	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	5.000000e-06
GCST011107_1	First year height change in growth hormone-treated short stature	6.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0000638	overall survival
EFO:0010969	response to growth hormone

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	3
methylmercuric chloride	decreases expression	2
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pirinixic acid	increases expression, affects binding, increases activity	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Carbamazepine	affects expression	1
Diazinon	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Gallic Acid	decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Quercetin	decreases expression	1

Clinical trials (associated diseases)

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