GM2A

Protein identityUniProt · HPA

UniProt accession

P17900

Gene

GM2A

Ensembl

ENSG00000196743

Chromosome

5

Canonical length

193 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Vesicles,Cytosol

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal enzyme beta-hexosaminidase A. Beta-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene result in GM2-gangliosidosis type AB or the AB variant of Tay-Sachs disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

Canonical amino-acid sequenceUniProt

193 residues, UniProt reviewed canonical sequence.

>P17900|GM2A
     1  MQSLMQAPLL IALGLLLAAP AQAHLKKPSQ LSSFSWDNCD EGKDPAVIRS LTLEPDPIIV
    61  PGNVTLSVMG STSVPLSSPL KVDLVLEKEV AGLWIKIPCT DYIGSCTFEH FCDVLDMLIP
   121  TGEPCPEPLR TYGLPCHCPF KEGTYSLPKS EFVVPDLELP SWLTTGNYRI ESVLSSSGKR
   181  LGCIKIAASL KGI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GM2A 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

77 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GM2A.

Disease | AllUniProt

Conditions GM2A is implicated in, by any mechanism.

• GM2-gangliosidosis AB (GM2GAB) MIM:272750

Disease | GeneticClinVar

19 pathogenic / likely-pathogenic of 238 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Tay-Sachs disease, variant AB
• Tay-Sachs disease

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)

1.28

gnomAD pLI

0.03

gnomAD missense Z

-0.3

DepMap mean gene effect

0.11

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

• ganglioside catabolic process
• glycosphingolipid catabolic process
• learning or memory
• lipid storage
• lipid transport
• neuromuscular process controlling balance
• oligosaccharide catabolic process

Molecular functions

• lipid transporter activity
• phospholipase activator activity
• beta-N-acetylgalactosaminidase activity
• sphingolipid activator protein activity

Cellular components

• apical plasma membrane
• azurophil granule lumen
• basolateral plasma membrane
• cytoplasmic side of plasma membrane
• cytosol
• extracellular exosome
• extracellular region
• lysosomal lumen

Protein domainsUniProt · Pfam · InterPro

• MD-2-related lipid-recognition domain
• ML domain
• Ganglioside GM2 activator
• GM2-AP, lipid-recognition domain superfamily

KeywordsUniProt

• Disulfide bond
• Gangliosidosis
• Glycoprotein
• Hydrolase
• Lipid metabolism
• Lysosome
• Signal
• Sphingolipid metabolism

InteractionsUniProt · HPA

Protein binding partners of GM2A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SORT1