B4GALT3

Summary

B4GALT3 (beta-1,4-galactosyltransferase 3, HGNC:926) is a protein-coding gene on chromosome 1q23.3, encoding Beta-1,4-galactosyltransferase 3 (O60512). Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.

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. This gene encodes an enzyme that may be mainly involved in the synthesis of the first N-acetyllactosamine unit of poly-N-acetyllactosamine chains. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 8703 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 50 total — 1 pathogenic
• MANE Select transcript: NM_003779

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:926
Approved symbol	B4GALT3
Name	beta-1,4-galactosyltransferase 3
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	beta4Gal-T3
Ensembl gene	ENSG00000158850
Ensembl biotype	protein_coding
OMIM	604014
Entrez	8703

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 46 protein_coding, 10 protein_coding_CDS_not_defined

ENST00000319769, ENST00000367998, ENST00000460415, ENST00000465740, ENST00000466504, ENST00000467863, ENST00000470882, ENST00000482288, ENST00000486938, ENST00000487004, ENST00000493164, ENST00000496313, ENST00000622395, ENST00000907550, ENST00000907551, ENST00000907552, ENST00000907553, ENST00000907554, ENST00000907555, ENST00000907556, ENST00000907557, ENST00000907558, ENST00000907559, ENST00000907560, ENST00000907561, ENST00000907562, ENST00000907563, ENST00000907564, ENST00000907565, ENST00000907566, ENST00000907567, ENST00000907568, ENST00000907569, ENST00000940281, ENST00000940282, ENST00000940283, ENST00000940284, ENST00000940285, ENST00000940286, ENST00000940287, ENST00000940288, ENST00000940289, ENST00000940290, ENST00000940291, ENST00000940292, ENST00000940293, ENST00000940294, ENST00000940295, ENST00000940296, ENST00000940297, ENST00000940298, ENST00000940299, ENST00000940300, ENST00000940301, ENST00000945764, ENST00000945765

RefSeq mRNA: 3 — MANE Select: NM_003779 NM_001199873, NM_001199874, NM_003779

CCDS: CCDS1222

Canonical transcript exons

ENST00000319769 — 8 exons

Exon	Start	End
ENSE00001352942	161176434	161176579
ENSE00001933506	161171310	161172089
ENSE00001935240	161177423	161177507
ENSE00003495327	161172227	161172331
ENSE00003498513	161175808	161176074
ENSE00003514889	161173859	161174049
ENSE00003554912	161173605	161173727
ENSE00003602753	161174993	161175228

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.9657 / max 172.8736, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15603	31.9657	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.72	gold quality
granulocyte	CL:0000094	96.32	gold quality
secondary oocyte	CL:0000655	96.24	gold quality
cortical plate	UBERON:0005343	94.92	gold quality
adenohypophysis	UBERON:0002196	94.70	gold quality
lower esophagus mucosa	UBERON:0035834	94.67	gold quality
pituitary gland	UBERON:0000007	94.13	gold quality
left ovary	UBERON:0002119	93.82	gold quality
omental fat pad	UBERON:0010414	93.81	gold quality
peritoneum	UBERON:0002358	93.79	gold quality
body of pancreas	UBERON:0001150	93.75	gold quality
body of stomach	UBERON:0001161	93.39	gold quality
right ovary	UBERON:0002118	93.22	gold quality
spleen	UBERON:0002106	93.11	gold quality
lymph node	UBERON:0000029	93.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.97	gold quality
left lobe of thyroid gland	UBERON:0001120	92.86	gold quality
minor salivary gland	UBERON:0001830	92.62	gold quality
upper lobe of left lung	UBERON:0008952	92.43	gold quality
metanephros cortex	UBERON:0010533	92.41	gold quality
right lobe of thyroid gland	UBERON:0001119	92.37	gold quality
skin of abdomen	UBERON:0001416	92.34	gold quality
mucosa of transverse colon	UBERON:0004991	92.25	gold quality
pancreas	UBERON:0001264	92.14	gold quality
thyroid gland	UBERON:0002046	92.14	gold quality
stomach	UBERON:0000945	92.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.06	gold quality
cardia of stomach	UBERON:0001162	91.99	gold quality
left uterine tube	UBERON:0001303	91.84	gold quality
upper lobe of lung	UBERON:0008948	91.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	1791.22
E-ANND-3	yes	13.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

miRNA regulators (miRDB)

38 targeting B4GALT3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-379-5P	97.52	67.81	485

Literature-anchored findings (GeneRIF, showing 11)

• B4GALT3, DAP3, RGS16, TMEM183A and UCK2–were significantly overexpressed in dup(1q)-positive ALLs compared with high hyperdiploid ALLs without dup(1q). (PMID:17613536)
• beta-1,4-Galactosyltransferase III enhances invasive phenotypes via beta1-integrin and predicts poor prognosis in neuroblastoma. (PMID:23444218)
• beta-1,4-Galactosyltransferase III suppresses beta1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer. (PMID:24403309)
• Data suggest that expression of B4GALT3 in placenta is up-regulated in third trimester; over-expression of B4GALT3 in cultured trophoblasts suppresses cell migration; thus, B4GALT3 appears to regulate trophoblast invasion in late stages of pregnancy. (PMID:25659296)
• our findings evidenced that B4GALT3 upregulated by miR-27a contributes to the tumorigenic activities by b1-integrin pathway and might provide potential biomarkers for cervical cancer. (PMID:26987623)
• The mutations c.1456C < T (p.L486F) in MYOC and c.322G < A (p.V108I) in B4GALT3 are likely responsible for the pathogenesis of Primary Open-angle Glaucoma in this family. (PMID:27900994)
• High-metastatic hepatocellular carcinoma cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of beta1-integrin-NF-kappaappaB metastatic signaling in fibroblasts resulting in lung cancer. (PMID:29335551)
• In bladder tumor cells circUBXN7 serves as a competitive endogenous RNA of miR-1247-3p to elevate B4GALT3 expression, consequently inhibiting cell viability and invasion. (PMID:30312173)
• These findings suggest that the transcription of the b4GalT3 gene is regulated by differential DNA binding of Sp3 and Sp1 in neuroblastoma and lung cancer. The increased expression of b4GalT3 in neuroblastoma may be ascribed to the enhanced expression of Sp3, which is observed for various cancers. (PMID:30561605)
• B4GALT3 promotes cell proliferation and invasion in glioblastoma. (PMID:32202233)
• Long noncoding RNA differentiation antagonizing nonprotein coding RNA promotes the proliferation, invasion and migration of neuroblastoma cells via targeting beta-1, 4-galactosyltransferase III by sponging miR-338-3p. (PMID:34050113)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	b4galt3	ENSDARG00000062329
mus_musculus	B4galt3	ENSMUSG00000052423
rattus_norvegicus	B4galt3	ENSRNOG00000003551
drosophila_melanogaster	beta4GalNAcTA	FBGN0027538
caenorhabditis_elegans	bre-4	WBGENE00000269

Paralogs (6): B4GALT7 (ENSG00000027847), B4GALT1 (ENSG00000086062), B4GALT2 (ENSG00000117411), B4GALT6 (ENSG00000118276), B4GALT4 (ENSG00000121578), B4GALT5 (ENSG00000158470)

Protein

Protein identifiers

Beta-1,4-galactosyltransferase 3 — O60512 (reviewed: O60512)

Alternative names: Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase, Beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase, N-acetyllactosamine synthase, Nal synthase, Neolactotriaosylceramide beta-1,4-galactosyltransferase, UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 3, UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 3

All UniProt accessions (2): A0A384NY44, O60512

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Found in various tissues. Highest expression in placenta, prostate, testis, ovary, intestine and muscle, and in fetal brain.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60512-1	1	yes
O60512-2	2

RefSeq proteins (3): NP_001186802, NP_001186803, NP_003770* (*=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

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)
• an N-acetyl-beta-D-glucosaminyl derivative + UDP-alpha-D-galactose = a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H(+) (RHEA:22932)
• 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)
• a neolactoside IV(3)-beta-GlcNAc-nLc4Cer + UDP-alpha-D-galactose = a neolactoside nLc6Cer + UDP + H(+) (RHEA:62548)
• a beta-D-glucosylceramide + UDP-alpha-D-galactose = a beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + UDP + H(+) (RHEA:62552)

UniProt features (26 total): binding site 10, glycosylation site 4, sequence conflict 3, topological domain 2, disulfide bond 2, splice variant 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60512-F1	88.72	0.73

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; 260–263; 291–293; 291; 303; 130–134; 169–171; 196–197; 197; 226

Disulfide bonds (2): 77–119, 190–209

Glycosylation sites (4): 57, 166, 337, 385

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: 195 (showing top): MORF_RAGE, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, KEGG_N_GLYCAN_BIOSYNTHESIS, DITTMER_PTHLH_TARGETS_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, MORF_FANCG, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, MODULE_206, GOBP_GLYCOSPHINGOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (6): carbohydrate metabolic process (GO:0005975), glucosylceramide metabolic process (GO:0006678), galactosylceramide biosynthetic process (GO:0006682), obsolete protein glycosylation (GO:0006486), lipid metabolic process (GO:0006629), obsolete glycosylation (GO:0070085)

GO Molecular Function (6): beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity (GO:0003831), N-acetyllactosamine synthase activity (GO:0003945), galactosyltransferase activity (GO:0008378), metal ion binding (GO:0046872), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (6): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), cytosol (GO:0005829), Golgi cisterna membrane (GO:0032580), extracellular exosome (GO:0070062), membrane (GO:0016020)

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
primary metabolic process	2
UDP-galactosyltransferase activity	2
cytoplasm	2
cellular anatomical structure	2
glycosylceramide metabolic process	1
galactosylceramide metabolic process	1
glycosphingolipid biosynthetic process	1
galactolipid biosynthetic process	1
ceramide biosynthetic process	1
hexosyltransferase activity	1
cation binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
Golgi cisterna	1
extracellular vesicle	1

Protein interactions and networks

STRING

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B4GALT3	B4GALNT2	Q8NHY0	839
B4GALT3	PRELP	P51888	763
B4GALT3	FUT8	Q9BYC5	486
B4GALT3	ST6GAL1	P15907	477
B4GALT3	B3GNT2	Q9NY97	445
B4GALT3	MGAT4B	Q9UQ53	444
B4GALT3	MGAT5B	Q3V5L5	438
B4GALT3	MGAT5	Q09328	437
B4GALT3	GALNT1	Q10472	434
B4GALT3	ST3GAL6	Q9Y274	431
B4GALT3	SLC35B3	Q9H1N7	423
B4GALT3	ST3GAL1	Q11201	422
B4GALT3	GALNT2	Q10471	414
B4GALT3	LMNB1	P20700	413
B4GALT3	MANEA	Q5SRI9	413

IntAct

63 interactions, top by confidence:

A	B	Type	Score
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
B4GALT3	SLC19A2	psi-mi:“MI:0914”(association)	0.530
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
CGRRF1	B4GALT3	psi-mi:“MI:0914”(association)	0.530
ATP6V0A2	B4GALT3	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
B4GALT3	ATP5MC1	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
GALNT6	B4GALT3	psi-mi:“MI:0914”(association)	0.530
B4GALT3	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
TMEM106A	B4GALT3	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.350
rep	B4GALT3	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CGRRF1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	RTL8C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (142): B4GALT3 (Affinity Capture-MS), B4GALT3 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), GHITM (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), POMGNT1 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), PON2 (Affinity Capture-MS), ATP5G1 (Affinity Capture-MS), REEP4 (Affinity Capture-MS), GPR89B (Affinity Capture-MS), UBE4A (Affinity Capture-MS), LMF1 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A4Z3, A1Y9I9, A4FUH1, B6CZ46, B6CZ56, B6CZ62, D3ZNQ3, G3V9Q9, O43505, O60512, O60909, O94766, P14616, P14617, P58158, Q09326, Q10469, Q2NKH9, Q2YDM8, Q3V1N9, Q3V5L5, Q4R5T7, Q5EA01, Q5EB73, Q5JU69, Q5M936, Q5NVN3, Q5R4S2, Q5R868, Q5YB40, Q5ZLK4, Q64716, Q6AYR4, Q765H6, Q7Z4J2, Q8BGT9, Q8BWP8, Q8IXK2, Q8NCL4, Q8R1J9

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2500825	NM_001122764.3(PPOX):c.420del (p.Glu141fs)	Pathogenic

SpliceAI

1499 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161172328:CACC:C	acceptor_gain	1.0000
1:161172330:CC:C	acceptor_gain	1.0000
1:161172331:CC:C	acceptor_gain	1.0000
1:161172332:C:CC	acceptor_gain	1.0000
1:161173728:C:CC	acceptor_gain	1.0000
1:161175225:CCCA:C	acceptor_gain	1.0000
1:161175226:CCA:C	acceptor_gain	1.0000
1:161175226:CCAC:C	acceptor_gain	1.0000
1:161175227:CAC:C	acceptor_gain	1.0000
1:161175229:C:CC	acceptor_gain	1.0000
1:161175230:T:A	acceptor_loss	1.0000
1:161175259:C:CT	acceptor_gain	1.0000
1:161175260:A:T	acceptor_gain	1.0000
1:161177419:ATACC:A	donor_loss	1.0000
1:161177420:TACC:T	donor_loss	1.0000
1:161177421:AC:A	donor_loss	1.0000
1:161172077:C:CT	acceptor_gain	0.9900
1:161172078:A:T	acceptor_gain	0.9900
1:161172214:T:TA	donor_gain	0.9900
1:161172221:TCCTA:T	donor_loss	0.9900
1:161172222:CCTA:C	donor_loss	0.9900
1:161172223:CTACC:C	donor_loss	0.9900
1:161172224:TACC:T	donor_loss	0.9900
1:161172225:ACCT:A	donor_loss	0.9900
1:161172226:C:CG	donor_loss	0.9900
1:161172227:C:G	donor_loss	0.9900
1:161172244:ATTGC:A	donor_gain	0.9900
1:161172329:ACC:A	acceptor_gain	0.9900
1:161172329:ACCC:A	acceptor_loss	0.9900
1:161172330:CCC:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000032128 (1:161172242 T>A), RS1000092132 (1:161173729 T>C), RS1000106201 (1:161173842 C>A), RS1000230179 (1:161178493 C>G,T), RS1000519821 (1:161179144 A>T), RS1001610761 (1:161171046 A>G), RS1002078161 (1:161177568 C>G), RS1002159189 (1:161176223 C>T), RS1002378203 (1:161174639 A>G), RS1002430612 (1:161174873 T>TCA), RS1002547162 (1:161171440 G>A), RS1003054244 (1:161177418 C>G), RS1003148846 (1:161177553 G>A,C,T), RS1003386195 (1:161176135 C>T), RS1003438883 (1:161176318 ATCTACTG>A)

Disease associations

OMIM: gene MIM:604014 | disease phenotypes: MIM:176200

GenCC curated gene-disease

Mondo (1): variegate porphyria (MONDO:0008297)

Orphanet (1): Variegate porphyria (Orphanet:79473)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003987_12	Asthma	5.000000e-15

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D046350	Porphyria, Variegate	C06.552.830.625; C16.320.850.742.625; C17.800.827.742.625; C18.452.811.400.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression, decreases methylation	3
bisphenol A	decreases expression, affects cotreatment, affects expression, increases abundance	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
arsenite	increases reaction, affects binding	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
abrine	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methotrexate	decreases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Phenobarbital	affects expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03338816	PHASE3	COMPLETED	ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
NCT02922413	PHASE2	TERMINATED	Panhematin for Prevention of Acute Attacks of Porphyria
NCT05854784	PHASE2	COMPLETED	Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP)
NCT01568554	Not specified	COMPLETED	Clinical Diagnosis of Acute Porphyria
NCT02935400	Not specified	ACTIVE_NOT_RECRUITING	Acute Porphyria Biomarkers for Disease Activity
NCT03547297	Not specified	TERMINATED	INSIGHT-AHP: A Study to Characterize the Prevalence of Acute Hepatic Porphyria (AHP) in Patients With Clinical Presentation and History Consistent With AHP