Seroatlas · Human Serome Atlas

LARGE1

Xylosyl- and glucuronyltransferase LARGE1

Also known as: KIAA0609, LARG1_HUMAN, LARGE

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O95461
Gene: LARGE1
Ensembl: ENSG00000133424
Chromosome: 22
Canonical length: 756 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a member of the N-acetylglucosaminyltransferase gene family. It encodes a glycosyltransferase which participates in glycosylation of alpha-dystroglycan, and may carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. It may also be involved in the addition of a repeated disaccharide unit. The protein encoded by this gene is the glycotransferase that adds the final xylose and glucuronic acid to alpha-dystroglycan and thereby allows alpha-dystroglycan to bind ligands including laminin 211 and neurexin. Mutations in this gene cause several forms of congenital muscular dystrophy characterized by cognitive disability and abnormal glycosylation of alpha-dystroglycan. Alternative splicing of this gene results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2018]

Canonical amino-acid sequenceUniProt

756 residues, UniProt reviewed canonical sequence.

>O95461|LARGE1
     1  MLGICRGRRK FLAASLSLLC IPAITWIYLF SGSFEDGKPV SLSPLESQAH SPRYTASSQR
    61  ERESLEVRMR EVEEENRALR RQLSLAQGRA PSHRRGNHSK TYSMEEGTGD SENLRAGIVA
   121  GNSSECGQQP VVEKCETIHV AIVCAGYNAS RDVVTLVKSV LFHRRNPLHF HLIADSIAEQ
   181  ILATLFQTWM VPAVRVDFYN ADELKSEVSW IPNKHYSGIY GLMKLVLTKT LPANLERVIV
   241  LDTDITFATD IAELWAVFHK FKGQQVLGLV ENQSDWYLGN LWKNHRPWPA LGRGYNTGVI
   301  LLLLDKLRKM KWEQMWRLTA ERELMGMLST SLADQDIFNA VIKQNPFLVY QLPCFWNVQL
   361  SDHTRSEQCY RDVSDLKVIH WNSPKKLRVK NKHVEFFRNL YLTFLEYDGN LLRRELFGCP
   421  SEADVNSENL QKQLSELDED DLCYEFRRER FTVHRTHLYF LHYEYEPAAD STDVTLVAQL
   481  SMDRLQMLEA ICKHWEGPIS LALYLSDAEA QQFLRYAQGS EVLMSRHNVG YHIVYKEGQF
   541  YPVNLLRNVA MKHISTPYMF LSDIDFLPMY GLYEYLRKSV IQLDLANTKK AMIVPAFETL
   601  RYRLSFPKSK AELLSMLDMG TLFTFRYHVW TKGHAPTNFA KWRTATTPYR VEWEADFEPY
   661  VVVRRDCPEY DRRFVGFGWN KVAHIMELDV QEYEFIVLPN AYMIHMPHAP SFDITKFRSN
   721  KQYRICLKTL KEEFQQDMSR RYGFAALKYL TAENNS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LARGE1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Other membrane
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.29
Highest tissue expression: 58 nTPM

Expression across tissuesHPA

Tissue

heart muscle: 58 nTPM
skeletal muscle: 46 nTPM
colon: 27 nTPM
tongue: 26 nTPM
cerebral cortex: 25 nTPM
choroid plexus: 25 nTPM

Single-cell type

podocytes: 2,027 nCPM
cardiomyocytes: 1,421 nCPM
choroid plexus epithelial cells: 907 nCPM
cone photoreceptor cells: 634 nCPM
myonuclei: 594 nCPM
brain excitatory neurons: 577 nCPM

Immune cell

naive B-cell: 1.2 nTPM
memory B-cell: 0.5 nTPM
MAIT T-cell: 0.3 nTPM
neutrophil: 0.3 nTPM
gdT-cell: 0.1 nTPM
NK-cell: 0.1 nTPM

Brain region

hippocampal formation: 126 nTPM
cerebral cortex: 99 nTPM
basal ganglia: 77 nTPM
choroid plexus: 73 nTPM
white matter: 63 nTPM
amygdala: 50 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LARGE1.

Disease | AllUniProt

Conditions LARGE1 is implicated in, by any mechanism.

Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B6 (MDDGB6) MIM:608840
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A6 (MDDGA6) MIM:613154

Disease | GeneticClinVar

41 pathogenic / likely-pathogenic of 1,011 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Muscular dystrophy-dystroglycanopathy type B6
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6
LARGE1-Related Disorders
See cases
Retinitis pigmentosa

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.3
gnomAD pLI: 0.99
DepMap mean gene effect: 0.09
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of LARGE1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads LARGE1 as an antibody target. Whether an autoantibody or antibody against LARGE1 could matter depends on whether native LARGE1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

LARGE1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label LARGE1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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