B4GALNT1

beta-1,4-N-acetyl-galactosaminyltransferase 1, the group of Beta 4-glycosyltransferases

Basic information

Region (hg38): 12:57623408-57633239

Previous symbols: [ "GALGT", "SPG26" ]

Links

ENSG00000135454 ∙ NCBI:2583 ∙ OMIM:601873 ∙ HGNC:4117 ∙ Uniprot:Q00973 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 26 (Moderate), mode of inheritance: AR
• hereditary spastic paraplegia 26 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 26 (Supportive), mode of inheritance: AR
• complex hereditary spastic paraplegia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 26, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23746551

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the B4GALNT1 gene.

• Spastic paraplegia (215 variants)
• not provided (72 variants)
• Inborn genetic diseases (26 variants)
• Hereditary spastic paraplegia 26 (15 variants)
• not specified (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the B4GALNT1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	63	5	71
missense	3		121	5	3	132
nonsense	6					6
start loss						0
frameshift	6	3				9
inframe indel			3			3
splice donor/acceptor (+/-2bp)		7				7
splice region			6	9	1	16
non coding			1	22	19	42
Total	15	10	128	90	27

Highest pathogenic variant AF is 0.0000263

Variants in B4GALNT1

This is a list of pathogenic ClinVar variants found in the B4GALNT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-57624077-G-A		not specified	Conflicting classifications of pathogenicity (Nov 01, 2022)
12-57624885-T-G			Likely benign (Nov 01, 2022)
12-57625419-C-T		not specified	Uncertain significance (May 04, 2022)
12-57626577-A-G			Benign (Jun 26, 2018)
12-57626742-C-T		not specified • B4GALNT1-related disorder	Benign (May 17, 2019)
12-57626748-T-G		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
12-57626789-C-G		Spastic paraplegia	Likely benign (Aug 10, 2023)
12-57626790-C-G		Spastic paraplegia	Uncertain significance (Aug 23, 2022)
12-57626799-G-A		not specified • Spastic paraplegia	Benign (Feb 01, 2024)
12-57626801-C-T		Spastic paraplegia • Inborn genetic diseases • Hereditary spastic paraplegia 26	Uncertain significance (Nov 27, 2023)
12-57626805-T-C		Spastic paraplegia	Uncertain significance (Jun 13, 2022)
12-57626813-G-A		Spastic paraplegia	Likely benign (Dec 22, 2023)
12-57626813-G-C		Spastic paraplegia	Uncertain significance (Aug 05, 2022)
12-57626832-C-T		Spastic paraplegia	Pathogenic (Feb 22, 2023)
12-57626833-G-A		Hereditary spastic paraplegia 26	Pathogenic (-)
12-57626837-C-T		Spastic paraplegia	Likely benign (Nov 07, 2023)
12-57626843-G-A		Spastic paraplegia	Likely benign (Jun 19, 2022)
12-57626856-C-G		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
12-57626858-G-A		Spastic paraplegia	Likely benign (May 20, 2022)
12-57626868-G-C		Spastic paraplegia	Pathogenic (Sep 20, 2022)
12-57626876-A-G		Spastic paraplegia	Likely benign (Nov 08, 2022)
12-57626891-G-A		Spastic paraplegia	Likely benign (Apr 14, 2023)
12-57626891-G-C		Spastic paraplegia	Benign/Likely benign (Dec 18, 2023)
12-57626900-A-AT		Spastic paraplegia	Pathogenic (Feb 08, 2019)
12-57626908-C-A		Spastic paraplegia	Uncertain significance (Aug 21, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
B4GALNT1	protein_coding	protein_coding	ENST00000341156	10	9946

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000393	0.991	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.924	267	313	0.853	0.0000194	3350
Missense in Polyphen		72	109.76	0.65597		1069
Synonymous	0.154	133	135	0.983	0.00000838	1173
Loss of Function	2.31	11	23.0	0.479	0.00000113	236

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000329	0.000236
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000169	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.000169	0.000163
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the biosynthesis of gangliosides GM2, GD2 and GA2. {ECO:0000269|PubMed:1601877}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:23746551}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosphingolipid biosynthesis - ganglio series - Homo sapiens (human);Ganglio Sphingolipid Metabolism;Metabolism of Spingolipids in ER and Golgi apparatus;Metabolism of lipids;Glycosphingolipid biosynthesis - ganglioseries;Metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.247

Intolerance Scores

• loftool: 0.489
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.52

Haploinsufficiency Scores

• pHI: 0.122
• hipred: Y
• hipred_score: 0.711
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.336

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: B4galnt1
• Phenotype: hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: ganglioside biosynthetic process;carbohydrate metabolic process;glycosphingolipid metabolic process;spermatogenesis;lipid storage;lipid glycosylation
• Cellular component: Golgi membrane;plasma membrane;membrane;integral component of Golgi membrane
• Molecular function: (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase activity