B4GALNT1

Summary

B4GALNT1 (beta-1,4-N-acetyl-galactosaminyltransferase 1, HGNC:4117) is a protein-coding gene on chromosome 12q13.3, encoding Beta-1,4 N-acetylgalactosaminyltransferase 1 (Q00973). Involved in the biosynthesis of gangliosides GM2, GD2, GT2 and GA2 from GM3, GD3, GT3 and GA3, respectively.

GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2583 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex hereditary spastic paraplegia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 400 total — 23 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_001478

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4117
Approved symbol	B4GALNT1
Name	beta-1,4-N-acetyl-galactosaminyltransferase 1
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	beta1-4GalNAc-T
Ensembl gene	ENSG00000135454
Ensembl biotype	protein_coding
OMIM	601873
Entrez	2583

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000341156, ENST00000418555, ENST00000449184, ENST00000547741, ENST00000548487, ENST00000548888, ENST00000549391, ENST00000550764, ENST00000550943, ENST00000551220, ENST00000551925, ENST00000552219, ENST00000552350, ENST00000552468, ENST00000552798, ENST00000553142, ENST00000882412, ENST00000954201, ENST00000954202

RefSeq mRNA: 19 — MANE Select: NM_001478 NM_001276468, NM_001276469, NM_001413967, NM_001413968, NM_001413969, NM_001413970, NM_001413971, NM_001413972, NM_001413973, NM_001413974, NM_001413977, NM_001413978, NM_001413979, NM_001413980, NM_001413981, NM_001413982, NM_001413983, NM_001413984, NM_001478

CCDS: CCDS61170, CCDS61171, CCDS8950

Canonical transcript exons

ENST00000341156 — 11 exons

Exon	Start	End
ENSE00001731418	57623409	57626961
ENSE00002359332	57632772	57633201
ENSE00003466193	57629048	57629146
ENSE00003476177	57631915	57632133
ENSE00003504019	57627618	57627858
ENSE00003524298	57628713	57628903
ENSE00003528825	57628122	57628262
ENSE00003551366	57630980	57631086
ENSE00003660366	57631200	57631364
ENSE00003684402	57630478	57630518
ENSE00003785583	57630152	57630332

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 97.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3396 / max 161.6275, expressed in 1045 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131714	8.6919	1012
131712	0.7363	292
131711	0.6351	290
131713	0.0868	47
131715	0.0712	27
131716	0.0667	36
131717	0.0516	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.39	gold quality
cerebellar hemisphere	UBERON:0002245	97.05	gold quality
cerebellar cortex	UBERON:0002129	96.86	gold quality
cortical plate	UBERON:0005343	96.24	gold quality
cerebellum	UBERON:0002037	93.98	gold quality
right frontal lobe	UBERON:0002810	93.87	gold quality
prefrontal cortex	UBERON:0000451	92.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.53	gold quality
ganglionic eminence	UBERON:0004023	92.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.62	gold quality
cingulate cortex	UBERON:0003027	90.61	gold quality
anterior cingulate cortex	UBERON:0009835	90.55	gold quality
neocortex	UBERON:0001950	89.00	gold quality
nucleus accumbens	UBERON:0001882	88.95	gold quality
frontal cortex	UBERON:0001870	88.88	gold quality
caudate nucleus	UBERON:0001873	88.74	gold quality
cerebral cortex	UBERON:0000956	87.59	gold quality
putamen	UBERON:0001874	87.41	gold quality
sural nerve	UBERON:0015488	86.84	gold quality
telencephalon	UBERON:0001893	86.69	gold quality
amygdala	UBERON:0001876	86.57	gold quality
primary visual cortex	UBERON:0002436	85.44	gold quality
Ammon’s horn	UBERON:0001954	85.32	gold quality
tibial nerve	UBERON:0001323	84.79	gold quality
brain	UBERON:0000955	84.76	gold quality
forebrain	UBERON:0001890	84.41	gold quality
central nervous system	UBERON:0001017	84.35	gold quality
stromal cell of endometrium	CL:0002255	84.09	gold quality
hypothalamus	UBERON:0001898	83.48	gold quality
endothelial cell	CL:0000115	83.40	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

45 targeting B4GALNT1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-193B-5P	97.91	65.88	837

Literature-anchored findings (GeneRIF, showing 19)

• The expression of three messengers coding for SAT-1, SAT-2 and GalNAcT-1 in human samples of intestinal cancer and some cell lines (breast cancer and melanomas), was evaluated. (PMID:17119850)
• Transmission disequilibrium test and case-control analysis did not detect an association of B4GALNT1 gene with T1DM. (PMID:19318031)
• GD2/GM2 is not a reliable biomarker in small cell lung carcinoma (PMID:19457569)
• Molecular upstaging of GalNAc-T using rt-pcr was correlated with prognosis in melanoma patients (PMID:21135695)
• Minimally disseminated disease in high risk retinoblastoma patients was detected using reverse transcriptase PCR for GD2 synthase mRNA in CSF. (PMID:23721779)
• The resukts of this study identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. (PMID:24103911)
• Novel B4GALNT1 mutations reported in two families with hereditary spastic paraplegia. (PMID:24283893)
• Data suggest that ganglioside glycosyltransferases ST3GAL5, ST8SIA1, and B4GALNT1 are S-acylated at conserved cysteine residues located close to cytoplasmic border of their transmembrane domains; ST3Gal-II is acylated at conserved cysteine residue in N-terminal cytoplasmic tail; for B4GALNT1 and ST3Gal-II, dimer formation controls their S-acylation status. (PMID:28698248)
• Since the nineties, mice lacking genes for single glycosyltransferases involved in ganglioside biosynthesis, including ST3GAL5 and B4GALNT1, were created and studied. The resulting phenotypes were frequently mild or very mild, so double knock-out animals were created to effectively study the function of gangliosides (PMID:29983310)
• Sp1 or HDAC1 knock down increased GM2-synthase transcription, and butyrate-mediated activation of GM2-synthase mRNA expression in SK-RC-45 cells was accompanied by Sp1 and HDAC1 loss from the +38/+187 region. Taken together, we have identified an epigenetic mechanism for the de-repression of the GM2-synthase gene in RCC. (PMID:30463940)
• Study analyzed enzyme activity and intracellular localization of the products of mutant cDNAs from eleven cases of hereditary spastic paraplegia with mutation in the coding region of B4GALNT1, and noted a lack of enzyme activity in a majority of them except two family cases. Then compared profiles of clinical findings of patients with hereditary spastic paraplegia and abnormal phenotypes of B4galnt-KO mice. (PMID:30521973)
• Data suggest that GD2 synthase (GD2) can well be considered as a diagnostic and prognostic marker in breast cancer. (PMID:31075227)
• High B4GALNT1 expression is associated with clear cell renal cell carcinoma metastasis. (PMID:31491435)
• B4GALNT1 enhanced tumorigenesis via induction of angiogenesis,ganglioside GM2/GD2 and cell motility. (PMID:31988291)
• B4GALNT1 promotes progression and metastasis in lung adenocarcinoma through JNK/c-Jun/Slug pathway. (PMID:33367717)
• Does GD2 synthase (GD2S) detect cancer stem cells in blood samples of breast carcinomas? (PMID:34907737)
• Functional validation of novel variants in B4GALNT1 associated with early-onset complex hereditary spastic paraplegia with impaired ganglioside synthesis. (PMID:35775650)
• B4GALNT1 promotes carcinogenesis by regulating epithelial-mesenchymal transition in hepatocellular carcinoma based on pan-cancer analysis. (PMID:37337736)
• Polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) isozyme surface charge governs charge substrate preferences to modulate mucin type O-glycosylation. (PMID:37555669)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	b4galnt1a	ENSDARG00000061520
danio_rerio	b4galnt1b	ENSDARG00000077352
mus_musculus	B4galnt1	ENSMUSG00000006731
rattus_norvegicus	B4galnt1	ENSRNOG00000004839

Paralogs (1): B4GALNT2 (ENSG00000167080)

Protein

Protein identifiers

Beta-1,4 N-acetylgalactosaminyltransferase 1 — Q00973 (reviewed: Q00973)

Alternative names: (N-acetylneuraminyl)-galactosylglucosylceramide, GM2/GD2 synthase, GalNAc-T

All UniProt accessions (9): B4DSP5, Q00973, F8VR44, F8VSE0, F8VU35, F8VW33, F8W1A7, H0YHT1, H0YI57

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the biosynthesis of gangliosides GM2, GD2, GT2 and GA2 from GM3, GD3, GT3 and GA3, respectively.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Golgi apparatus membrane.

Disease relevance. Spastic paraplegia 26, autosomal recessive (SPG26) [MIM:609195] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG26 is a complicated form characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional features include intellectual disability, peripheral neuropathy, dysarthria, cerebellar signs, extrapyramidal signs, and cortical atrophy. The disorder is slowly progressive. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Sphingolipid metabolism.

Similarity. Belongs to the glycosyltransferase 2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q00973-1	1	yes
Q00973-2	2
Q00973-3	3

RefSeq proteins (19): NP_001263397, NP_001263398, NP_001400896, NP_001400897, NP_001400898, NP_001400899, NP_001400900, NP_001400901, NP_001400902, NP_001400903, NP_001400906, NP_001400907, NP_001400908, NP_001400909, NP_001400910, NP_001400911, NP_001400912, NP_001400913, NP_001469* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001173	Glyco_trans_2-like	Domain
IPR011143	GM2_synthase	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF00535

Enzyme classification (BRENDA):

• EC 2.4.1.92 — (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase (BRENDA: 8 organisms, 60 substrates, 14 inhibitors, 20 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-N-ACETYL-D-GALACTOSAMINE	0.007–0.082	6
GM3	0.0166–0.19	3
UDP-GALNAC	0.097–0.19	2
GANGLIOSIDE GD3	0.152	1
GANGLIOSIDE GM3	0.385	1
GD3(N-ACETYLNEURAMINIC ACID)	0.35	1
GD3(N-GLYCOLYLNEURAMINIC ACID)-GANGLIOSIDE	0.027	1
GM3(N-ACETYLNEURAMINIC ACID)	2.1	1
GM3(N-GLYCOLYLNEURAMINIC ACID)	0.16	1
P-NITROPHENYL-GLCNAC	0.38	1
UDP-N-ACETYLGALACTOSAMINE	1.64	1

Catalyzed reactions (Rhea), 9 shown:

• a ganglioside GM3 (d18:1(4E)) + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GM2 (d18:1(4E)) + UDP + H(+) (RHEA:12588)
• a ganglioside GD3 (d18:1(4E)) + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GD2 (d18:1(4E)) + UDP + H(+) (RHEA:41816)
• a ganglioside GM3 + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GM2 + UDP + H(+) (RHEA:43268)
• a ganglioside GD3 + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GD2 + UDP + H(+) (RHEA:43272)
• a ganglioside GD1a + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GalNAc-GD1a + UDP + H(+) (RHEA:43276)
• a neolactoside IV(3)-alpha-NeuGc-nLc4Cer + UDP-N-acetyl-alpha-D-galactosamine = a neolactoside IV(4)-beta-GalNAc-IV(3)-alpha-NeuGc-nLc4Cer + UDP + H(+) (RHEA:43300)
• a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GA2 (d18:1(4E)) + UDP + H(+) (RHEA:47564)
• a ganglioside GT3 (d18:1(4E)) + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GT2 (d18:1(4E)) + UDP + H(+) (RHEA:47580)
• a beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + UDP-N-acetyl-alpha-D-galactosamine = a ganglioside GA2 + UDP + H(+) (RHEA:62516)

UniProt features (20 total): disulfide bond 5, sequence variant 5, splice variant 3, glycosylation site 3, topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9H6L	X-RAY DIFFRACTION	2.67
9H6K	X-RAY DIFFRACTION	2.75
9H6J	X-RAY DIFFRACTION	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00973-F1	88.79	0.70

Functional residue map

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

Disulfide bonds (5): 429–476, 529, 80, 82, 412

Glycosylation sites (3): 79, 179, 274

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9840309	Glycosphingolipid biosynthesis
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 305 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, BENPORATH_ES_WITH_H3K27ME3, TSENG_IRS1_TARGETS_UP, GOBP_BEHAVIOR, GOBP_VACUOLE_ORGANIZATION, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, CMYB_01, AAGCCAT_MIR135A_MIR135B, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, RAMALHO_STEMNESS_DN, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (14): ganglioside biosynthetic process (GO:0001574), carbohydrate metabolic process (GO:0005975), glycosphingolipid metabolic process (GO:0006687), vacuole organization (GO:0007033), spermatogenesis (GO:0007283), determination of adult lifespan (GO:0008340), lipid storage (GO:0019915), nerve development (GO:0021675), limb development (GO:0060173), motor behavior (GO:0061744), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), obsolete lipid glycosylation (GO:0030259), carbohydrate derivative biosynthetic process (GO:1901137)

GO Molecular Function (5): (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase activity (GO:0003947), acetylgalactosaminyltransferase activity (GO:0008376), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	2
ganglioside metabolic process	1
glycosphingolipid biosynthetic process	1
ceramide biosynthetic process	1
glycolipid metabolic process	1
sphingolipid metabolic process	1
organelle organization	1
developmental process involved in reproduction	1
male gamete generation	1
multicellular organismal process	1
nutrient storage	1
nervous system development	1
anatomical structure development	1
appendage development	1
behavior	1
lipid metabolic process	1
biosynthetic process	1
carbohydrate derivative metabolic process	1
acetylgalactosaminyltransferase activity	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B4GALNT1	CHPF	Q8IZ52	872
B4GALNT1	ETFA	P13804	871
B4GALNT1	ST8SIA1	Q92185	857
B4GALNT1	GALNT1	Q10472	855
B4GALNT1	GALNT8	Q9NY28	850
B4GALNT1	GALNT6	Q8NCL4	847
B4GALNT1	KIF5A	Q12840	836
B4GALNT1	CHSY1	Q86X52	835
B4GALNT1	GALNT4	Q8N4A0	831
B4GALNT1	GALNT2	Q10471	815
B4GALNT1	GALNT13	Q8IUC8	814
B4GALNT1	GALNT3	Q14435	813
B4GALNT1	B3GALT4	O96024	716
B4GALNT1	CHPF2	Q9P2E5	675
B4GALNT1	NPC1	O15118	674

IntAct

30 interactions, top by confidence:

A	B	Type	Score
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
TMED6	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
PCDH20		psi-mi:“MI:0914”(association)	0.350
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350
ITM2B	SEMA4F	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	FAM234B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
PCDH20	PCDH17	psi-mi:“MI:0914”(association)	0.350
ITM2B	HS6ST1	psi-mi:“MI:0914”(association)	0.350
PCDHGA6	GOSR1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
CHRNB1	CLGN	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-RNA), B4GALNT1 (Proximity Label-MS), B4GALNT1 (Affinity Capture-Western), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4M2, A4IFG4, A5D8P8, A6NKD9, A7E2M3, B4F7F3, E9Q6B2, F1MX48, F1SAM7, O97676, P18065, P36956, P47877, P49705, P56720, P56873, Q00709, Q00973, Q09200, Q0IHY5, Q15465, Q24JP5, Q2YD98, Q3TAS6, Q58CS8, Q5QQ49, Q5UCC4, Q60416, Q60698, Q641Q3, Q68FE7, Q6AYH6, Q6DVA0, Q6P7K5, Q6UKI2, Q6WVG3, Q80WF4, Q8IW70, Q8JGM4, Q8K064

Diamond homologs: Q00973, Q09199, Q09200, Q10468, Q8NHY0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	11
Uncertain significance	178
Likely benign	133
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074269	NM_001478.5(B4GALNT1):c.1514G>A (p.Arg505His)	Pathogenic
1451812	NM_001478.5(B4GALNT1):c.263del (p.Gly88fs)	Pathogenic
1452136	NM_001478.5(B4GALNT1):c.661C>T (p.Gln221Ter)	Pathogenic
2110770	NM_001478.5(B4GALNT1):c.1478C>G (p.Ser493Ter)	Pathogenic
2123385	NM_001478.5(B4GALNT1):c.702dup (p.Ala235fs)	Pathogenic
2143659	NM_001478.5(B4GALNT1):c.909C>A (p.Tyr303Ter)	Pathogenic
2304141	NM_001478.5(B4GALNT1):c.863_870dup (p.Arg291fs)	Pathogenic
2573474	NM_001478.5(B4GALNT1):c.584del (p.Gly195fs)	Pathogenic
2695094	NM_001478.5(B4GALNT1):c.1417dup (p.Val473fs)	Pathogenic
2827828	NM_001478.5(B4GALNT1):c.1431del (p.Asp478fs)	Pathogenic
3369026	NM_001478.5(B4GALNT1):c.532-1G>C	Pathogenic
3653512	NM_001478.5(B4GALNT1):c.942_952del (p.Ser314fs)	Pathogenic
3655318	NM_001478.5(B4GALNT1):c.1008G>A (p.Trp336Ter)	Pathogenic
3683789	NM_001478.5(B4GALNT1):c.380C>A (p.Ser127Ter)	Pathogenic
3708535	NM_001478.5(B4GALNT1):c.1167dup (p.Ser390fs)	Pathogenic
4081205	NM_001478.5(B4GALNT1):c.1458dup (p.Leu487fs)	Pathogenic
4798696	NM_001478.5(B4GALNT1):c.1435dup (p.Val479fs)	Pathogenic
60523	NM_001478.5(B4GALNT1):c.395del (p.Pro132fs)	Pathogenic
60524	NM_001478.5(B4GALNT1):c.682C>T (p.Arg228Ter)	Pathogenic
60526	NM_001478.5(B4GALNT1):c.358C>T (p.Gln120Ter)	Pathogenic
653998	NM_001478.5(B4GALNT1):c.292C>T (p.Arg98Ter)	Pathogenic
852385	NM_001478.5(B4GALNT1):c.1445dup (p.Asp482fs)	Pathogenic
989143	NM_001478.5(B4GALNT1):c.1415G>C (p.Arg472Pro)	Pathogenic
1176600	NM_001478.5(B4GALNT1):c.383+1G>A	Likely pathogenic
1338617	NM_001478.5(B4GALNT1):c.515_518delinsAC (p.Gly172fs)	Likely pathogenic
2312523	NM_001478.5(B4GALNT1):c.384-1G>A	Likely pathogenic
2582464	NM_001478.5(B4GALNT1):c.532-2_532-1delinsTC	Likely pathogenic
2682932	NM_001478.5(B4GALNT1):c.713-1G>A	Likely pathogenic
2769134	NM_001478.5(B4GALNT1):c.811+38_903del	Likely pathogenic
2861081	NM_001478.5(B4GALNT1):c.712+1G>A	Likely pathogenic

SpliceAI

3948 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57624099:G:GG	donor_gain	1.0000
12:57624865:GCT:G	acceptor_gain	1.0000
12:57624865:GCTC:G	acceptor_gain	1.0000
12:57625234:A:AG	acceptor_gain	1.0000
12:57625235:G:GG	acceptor_gain	1.0000
12:57626960:TT:T	acceptor_gain	1.0000
12:57626960:TTC:T	acceptor_loss	1.0000
12:57626961:TC:T	acceptor_loss	1.0000
12:57626962:C:CC	acceptor_gain	1.0000
12:57626962:CTGGG:C	acceptor_loss	1.0000
12:57626963:T:A	acceptor_loss	1.0000
12:57628116:CCCTA:C	donor_loss	1.0000
12:57628117:CCTA:C	donor_loss	1.0000
12:57628118:CTAC:C	donor_loss	1.0000
12:57628119:TAC:T	donor_loss	1.0000
12:57628120:A:AC	donor_gain	1.0000
12:57628121:C:CC	donor_gain	1.0000
12:57628121:C:CT	donor_loss	1.0000
12:57628150:T:TA	donor_gain	1.0000
12:57628745:AGGGG:A	donor_gain	1.0000
12:57628757:CGCG:C	donor_gain	1.0000
12:57628899:CTGGG:C	acceptor_gain	1.0000
12:57628904:C:CC	acceptor_gain	1.0000
12:57628910:T:TC	acceptor_gain	1.0000
12:57629050:C:A	donor_gain	1.0000
12:57629147:C:CC	acceptor_gain	1.0000
12:57630331:ACCTA:A	acceptor_loss	1.0000
12:57630333:C:CA	acceptor_loss	1.0000
12:57630334:T:C	acceptor_loss	1.0000
12:57631914:CCCCA:C	donor_gain	1.0000

AlphaMissense

3402 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57627691:G:C	N437K	0.999
12:57627691:G:T	N437K	0.999
12:57628183:A:G	F361S	0.999
12:57628863:C:A	K284N	0.999
12:57628863:C:G	K284N	0.999
12:57626923:A:G	S475P	0.998
12:57627649:G:C	F451L	0.998
12:57627649:G:T	F451L	0.998
12:57627651:A:G	F451L	0.998
12:57628192:T:A	D358V	0.998
12:57628205:A:G	W354R	0.998
12:57628205:A:T	W354R	0.998
12:57628254:G:C	F337L	0.998
12:57628254:G:T	F337L	0.998
12:57628256:A:G	F337L	0.998
12:57628879:A:T	V279D	0.998
12:57626899:G:C	H483D	0.997
12:57628123:A:G	L381P	0.997
12:57628192:T:C	D358G	0.997
12:57628192:T:G	D358A	0.997
12:57628195:T:A	D357V	0.997
12:57628198:T:A	D356V	0.997
12:57628207:A:G	L353P	0.997
12:57628259:A:G	W336R	0.997
12:57628259:A:T	W336R	0.997
12:57628783:G:T	A311D	0.997
12:57626897:A:C	H483Q	0.996
12:57626897:A:T	H483Q	0.996
12:57626955:A:C	F464C	0.996
12:57627685:G:C	F439L	0.996

dbSNP variants (sampled 300 via entrez): RS1000799359 (12:57633667 T>C,G), RS1001133168 (12:57634089 C>A,G,T), RS1001302779 (12:57624035 G>A), RS1001464655 (12:57627392 C>CA), RS1001562599 (12:57624350 C>A), RS1002296345 (12:57634515 T>C), RS1002475064 (12:57628050 C>T), RS1002787958 (12:57629936 G>C,T), RS1002832673 (12:57628365 C>T), RS1003208836 (12:57629639 G>T), RS1004152351 (12:57627265 G>C,T), RS1005557581 (12:57631834 T>C), RS1005578101 (12:57628455 G>A,T), RS1005586370 (12:57634986 C>T), RS1005656602 (12:57634658 A>T)

Disease associations

OMIM: gene MIM:601873 | disease phenotypes: MIM:609195, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 26	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex hereditary spastic paraplegia	Definitive	AR

Mondo (2): hereditary spastic paraplegia 26 (MONDO:0012213), autism (MONDO:0005260)

Orphanet (1): Autosomal recessive spastic paraplegia type 26 (Orphanet:101006)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000079	Abnormality of the urinary system
HP:0000518	Cataract
HP:0000639	Nystagmus
HP:0000712	Emotional lability
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001288	Gait disturbance
HP:0001310	Dysmetria
HP:0001317	Abnormal cerebellum morphology
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001761	Pes cavus
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002120	Cerebral cortical atrophy
HP:0002359	Frequent falls
HP:0002495	Impaired vibratory sensation
HP:0002650	Scoliosis
HP:0003202	Skeletal muscle atrophy
HP:0003484	Upper limb muscle weakness
HP:0003487	Babinski sign
HP:0003593	Infantile onset
HP:0003676	Progressive

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010041_2	Cortical thickness	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004840	cortical thickness

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
C536862	Spastic paraplegia 26, autosomal recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	increases expression, increases methylation	3
lead acetate	increases expression	2
sulforaphane	increases expression	2
Estradiol	affects cotreatment, increases expression	2
Smoke	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
bisphenol S	increases methylation	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
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Troglitazone	increases expression	1
Arsenic	increases abundance, increases expression	1
Diethylnitrosamine	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1
N-Nitrosopyrrolidine	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_EI09	Hep-G2 SimpleCell O-GalNAc KO GalNAc-T1	Cancer cell line	Male
CVCL_XL88	HAP1 B4GALNT1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms