LARGE2

LARGE xylosyl- and glucuronyltransferase 2, the group of Glycosyltransferase family 8

Basic information

Region (hg38): 11:45921621-45929096

Previous symbols: [ "GYLTL1B" ]

Links

ENSG00000165905 ∙ NCBI:120071 ∙ OMIM:609709 ∙ HGNC:16522 ∙ Uniprot:Q8N3Y3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LARGE2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LARGE2 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						0
missense			8	1		9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	1	0

Variants in LARGE2

This is a list of pathogenic ClinVar variants found in the LARGE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-45923512-A-T		not specified	Uncertain significance (Jul 06, 2021)
11-45924549-A-G		not specified	Uncertain significance (Jun 18, 2021)
11-45926234-G-A		not specified	Uncertain significance (Oct 12, 2021)
11-45926501-C-G		not specified	Uncertain significance (Oct 26, 2021)
11-45926548-G-A		not specified	Uncertain significance (Oct 26, 2021)
11-45926763-G-A		not specified	Uncertain significance (Jun 22, 2021)
11-45927439-C-T		not specified	Uncertain significance (Aug 16, 2021)
11-45928194-G-A		not specified	Likely benign (Jun 18, 2021)
11-45928344-T-C		not specified	Uncertain significance (Aug 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LARGE2	protein_coding	protein_coding	ENST00000531526	13	7476

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.60e-12	0.560	125669	1	78	125748	0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0646	409	405	1.01	0.0000267	4594
Missense in Polyphen		137	137.56	0.99592		1535
Synonymous	-0.312	177	172	1.03	0.0000110	1539
Loss of Function	1.46	23	31.9	0.721	0.00000161	343

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000960	0.000959
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000284	0.000281
Middle Eastern	0.000163	0.000163
South Asian	0.000457	0.000425
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Bifunctional glycosyltransferase with both xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine- beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1). Phosphorylated O-mannosyl trisaccharid is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide. Has a higher activity toward alpha-dystroglycan than LARGE. {ECO:0000269|PubMed:15661757, ECO:0000269|PubMed:15752776, ECO:0000269|PubMed:25138275}.
• Pathway: Mannose type O-glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• rvis_EVS: -1.24
• rvis_percentile_EVS: 5.52

Haploinsufficiency Scores

• pHI: 0.266
• hipred: N
• hipred_score: 0.238
• ghis: 0.506

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Large2
• Phenotype: normal phenotype

Zebrafish Information Network

• Gene name: large2
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: deformed

Gene ontology

• Biological process: protein O-linked glycosylation;protein O-linked mannosylation;muscle cell cellular homeostasis
• Cellular component: Golgi membrane;Golgi apparatus;integral component of membrane
• Molecular function: protein binding;glucuronosyltransferase activity;transferase activity, transferring glycosyl groups;manganese ion binding;UDP-xylosyltransferase activity;xylosyltransferase activity