GM2A ganglioside GM2 activator [Homo sapiens (human)] - Gene

Summary

Official Symbol: GM2Aprovided by HGNC
Official Full Name: ganglioside GM2 activatorprovided by HGNC
Primary source: HGNC:HGNC:4367
See related: Ensembl:ENSG00000196743 MIM:613109; AllianceGenome:HGNC:4367
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GM2AP; SAP-3; GM2-AP
Summary: 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]
Expression: Ubiquitous expression in skin (RPKM 39.8), placenta (RPKM 38.5) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q33.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (151253185..151270440)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (151792130..151809386)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (150632746..150650001)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Two patients from Turkey with a novel variant in the GM2A gene and review of the literature.
Title: Two patients from Turkey with a novel variant in the GM2A gene and review of the literature.
GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells.
Title: GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells.
Review of GM2A mutations causing GM2 activator protein deficiency and GM2 gangliosidosis-AB variant.
Title: GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review.
Studies indicate that sphingolipid activator proteins (SAPs) and anionic lipids are essential stimulators to reach physiological rates of lysosomal sphingolipid degradation.
Title: Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism.
this study has established the potential role of GM2A in breast cancer progression
Title: Identification of ganglioside GM2 activator playing a role in cancer cell migration through proteomic analysis of breast cancer secretomes.
Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies
Title: Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity.
Gene polymorphisms of MD2 and GM2A were associated with the occurrence or severity of neonatal necrotizing enterocolitis.
Title: Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.
In vitro assays with the isolated H1 or H2 homodimers (beta-alpha hybrid construct of beta-hexosaminidase A subunits) confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside.
Title: In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.
impact of GM2AP on glucose metabolism
Title: Adipokine ganglioside GM2 activator protein stimulates insulin secretion.
Treatment of meniscal explants with IL-1RA inhibited the expression of many catabolic genes following a single bout of high dynamic strain.
Title: In vitro inhibition of compression-induced catabolic gene expression in meniscal explants following treatment with IL-1 receptor antagonist.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Tay-Sachs disease, variant AB MedGen: C0268275 OMIM: 272750 GeneReviews: GM2 Activator Deficiency	Compare labs

EBI GWAS Catalog

Description
Genetic variants associated with disordered eating. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of GM2 ganglioside activator (GM2A) by siRNA enhances HIV-1 replication in HeLa P4/R5 cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GM2A_1758 (e-PCR)
- UniSTS:277287

D8S2279 (e-PCR)
- UniSTS:473907

WI-10510 (e-PCR)
- UniSTS:44887

GDB:194298 (e-PCR)
- UniSTS:155790

D5S2404 (e-PCR)
- UniSTS:48329

D3S3426 (e-PCR)
- UniSTS:13806

RH77939 (e-PCR)
- UniSTS:48366

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables beta-N-acetylgalactosaminidase activity	IEA Inferred from Electronic Annotation more info
enables lipid transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables phospholipase activator activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sphingolipid activator protein activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in ganglioside catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycosphingolipid catabolic process	TAS Traceable Author Statement more info
involved_in learning or memory	IEA Inferred from Electronic Annotation more info
involved_in lipid storage	IEA Inferred from Electronic Annotation more info
involved_in lipid transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in maintenance of location in cell	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
involved_in oligosaccharide catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in azurophil granule lumen	TAS Traceable Author Statement more info
located_in basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasmic side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in lysosomal lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: ganglioside GM2 activator

Names: GM2 ganglioside activator; GM2-activator protein; cerebroside sulfate activator protein; shingolipid activator protein 3; sphingolipid activator protein 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009059.1 RefSeqGene

Range

5134..22389

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000405.5 → NP_000396.2 ganglioside GM2 activator isoform 1 precursor

See identical proteins and their annotated locations for NP_000396.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC008385, BM834780, X61095

Consensus CDS

CCDS4313.1

UniProtKB/Swiss-Prot

B2R699, D3DQH6, P17900, Q14426, Q14428, Q6LBL5

Related

ENSP00000349687.3, ENST00000357164.4

Conserved Domains (1) summary

cd00258
Location:32 → 193

GM2-AP; GM2 activator protein (GM2-AP) is a non-enzymatic lysosomal protein that acts as cofactor in the sequential degradation of gangliosides. GM2A is an essential cofactor for beta-hexosaminidase A (Hex A) in the enzymatic hydrolysis of GM2 ganglioside to GM3. ...
NM_001167607.3 → NP_001161079.1 ganglioside GM2 activator isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AC008385

UniProtKB/TrEMBL

B4DQM5

Conserved Domains (1) summary

cl00274
Location:32 → 140

ML; The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, Niemann-Pick type C2 (Npc2) protein, phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP), mite allergen Der p 2 and several proteins of ...