HEXA hexosaminidase subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: HEXAprovided by HGNC
Official Full Name: hexosaminidase subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:4878
See related: Ensembl:ENSG00000213614 MIM:606869; AllianceGenome:HGNC:4878
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: TSD
Summary: This gene encodes a member of the glycosyl hydrolase 20 family of proteins. The encoded preproprotein is proteolytically processed to generate the alpha subunit of the lysosomal enzyme beta-hexosaminidase. This enzyme, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene lead to an accumulation of GM2 ganglioside in neurons, the underlying cause of neurodegenerative disorders termed the GM2 gangliosidoses, including Tay-Sachs disease (GM2-gangliosidosis type I). Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
Expression: Ubiquitous expression in placenta (RPKM 36.4), thyroid (RPKM 34.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q23

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (72340924..72376014, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (70157399..70192818, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (72633265..72668355, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Biochemical and mutational analyses of HEXA in a cohort of Egyptian patients with infantile Tay-Sachs disease. Expansion of the mutation spectrum.
Title: Biochemical and mutational analyses of HEXA in a cohort of Egyptian patients with infantile Tay-Sachs disease. Expansion of the mutation spectrum.
Analysis of the HEXA, HEXB, ARSA, and SMPD1 Genes in 68 Iranian Patients.
Title: Analysis of the HEXA, HEXB, ARSA, and SMPD1 Genes in 68 Iranian Patients.
Novel HEXA variants in Korean children with Tay-Sachs disease with regression of neurodevelopment from infancy.
Title: Novel HEXA variants in Korean children with Tay-Sachs disease with regression of neurodevelopment from infancy.
In-silico screening and microsecond molecular dynamics simulations to identify single point mutations that destabilize beta-hexosaminidase A causing Tay-Sachs disease.
Title: In-silico screening and microsecond molecular dynamics simulations to identify single point mutations that destabilize β-hexosaminidase A causing Tay-Sachs disease.
Tay-Sachs Disease: Two Novel Rare HEXA Mutations from Pakistan and Morocco.", trans "Tay-Sachs-Syndrom: zwei neue, seltene HEXA-Mutationen aus Pakistan und Marokko.
Title: Tay-Sachs Disease: Two Novel Rare HEXA Mutations from Pakistan and Morocco.
Novel bicistronic lentiviral vectors correct beta-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis.
Title: Novel bicistronic lentiviral vectors correct β-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis.
The study characterized 34 enzymatically confirmed Tay-Sachs disease (TSD) families to investigate the presence of novel as well as known variants in HEXA gene. There were detected 25 variants belonging to 31 affected TSD patients and 3 carrier couples confirmed by enzyme study.
Title: Identification of novel variants in a large cohort of children with Tay-Sachs disease: An initiative of a multicentric task force on lysosomal storage disorders by Government of India.
Use of MLPA assay for detecting large copy number changes in the HEXA gene.
Title: Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India.
Reported data present, for the first time, reference values for urinary activities of HEX and its isoenzymes HEX A and HEX B in children and adolescent.
Title: Pediatric reference data on activity of urinary N-acetyl-β-D-hexosaminidase and its isoenzymes.
The alpha mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type alpha. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA beta chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum to the cytosol and are degraded by the ...
Title: Tay-Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum-associated degradation.

Submit: New GeneRIF Correction See all GeneRIFs (41)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Tay-Sachs disease MedGen: C0039373 OMIM: 272800 GeneReviews: HEXA Disorders	Compare labs

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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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 Nef ultimately increases the secretion of hexosaminidases due to impairment of GCC2-Rab9 mediated IGF2R (CI-MPR) containing transport vesicles to trans Golgi network from late endosomes	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

RH98547 (e-PCR)
- UniSTS:84233

SHGC-33452 (e-PCR)
- UniSTS:33294

RH118806 (e-PCR)
- UniSTS:138787

WI-7120 (e-PCR)
- UniSTS:39231

GDB:177773 (e-PCR)
- UniSTS:154958

GDB:186545 (e-PCR)
- UniSTS:155489

GDB:186546 (e-PCR)
- UniSTS:155490

RH44590 (e-PCR)
- UniSTS:9334

GDB:176311 (e-PCR)
- UniSTS:154791

GDB:176312 (e-PCR)
- UniSTS:154792

GDB:177101 (e-PCR)
- UniSTS:154832

SHGC-35689 (e-PCR)
- UniSTS:44011

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables N-acetyl-beta-D-galactosaminidase activity	IEA Inferred from Electronic Annotation more info
enables acetylglucosaminyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables beta-N-acetylhexosaminidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables beta-N-acetylhexosaminidase activity	IDA Inferred from Direct Assay more info	PubMed
enables beta-N-acetylhexosaminidase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in adult walking behavior	IEA Inferred from Electronic Annotation more info
involved_in carbohydrate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in cell morphogenesis involved in neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in dermatan sulfate catabolic process	IEA Inferred from Electronic Annotation more info
involved_in ganglioside catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in ganglioside catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glycosaminoglycan biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glycosaminoglycan metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycosaminoglycan metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in hyaluronan catabolic process	IEA Inferred from Electronic Annotation more info
involved_in lipid storage	IEA Inferred from Electronic Annotation more info
involved_in lysosome organization	IEA Inferred from Electronic Annotation more info
involved_in maintenance of location in cell	IEA Inferred from Electronic Annotation more info
involved_in myelination	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular process controlling posture	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in sexual reproduction	IEA Inferred from Electronic Annotation more info
involved_in skeletal system development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in azurophil granule	IDA Inferred from Direct Assay more info	PubMed
part_of beta-N-acetylhexosaminidase complex	IDA Inferred from Direct Assay more info	PubMed
part_of beta-N-acetylhexosaminidase complex	IPI Inferred from Physical Interaction more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in extracellular exosome	HDA more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in lysosomal lumen	NAS Non-traceable Author Statement more info	PubMed
located_in lysosomal lumen	TAS Traceable Author Statement more info
is_active_in lysosome	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	HDA more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: beta-hexosaminidase subunit alpha

Names: N-acetyl-beta-glucosaminidase subunit alpha; beta-N-acetylhexosaminidase subunit alpha; hexosaminidase A (alpha polypeptide); hexosaminidase subunit A

NP_000511.2

EC 3.2.1.52

NP_001305754.1

EC 3.2.1.52

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_009017.3 RefSeqGene

Range

5000..40090

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000520.6 → NP_000511.2 beta-hexosaminidase subunit alpha isoform 2 preproprotein

See identical proteins and their annotated locations for NP_000511.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC009690, BC018927, BM668409, DC356933

Consensus CDS

CCDS10243.1

UniProtKB/Swiss-Prot

B4DKE7, E7ENH7, P06865, Q53HS8, Q6AI32

UniProtKB/TrEMBL

A0A0S2Z3W3, B4DVA7

Related

ENSP00000268097.6, ENST00000268097.10

Conserved Domains (2) summary

cd06562
Location:167 → 511

GH20_HexA_HexB-like; Beta-N-acetylhexosaminidases catalyze the removal of beta-1,4-linked N-acetyl-D-hexosamine residues from the non-reducing ends of N-acetyl-beta-D-hexosaminides including N-acetylglucosides and N-acetylgalactosides. The hexA and hexB genes encode the ...

pfam14845
Location:23 → 145

Glycohydro_20b2; beta-acetyl hexosaminidase like
NM_001318825.2 → NP_001305754.1 beta-hexosaminidase subunit alpha isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). The encoded isoform (1) may undergo proteolytic processing similar to isoform 2.

Source sequence(s)

AC009690, AK301000, BM668409, DC356933, M13520

Consensus CDS

CCDS81905.1

UniProtKB/TrEMBL

B4DVA7, H3BP20

Related

ENSP00000455114.1, ENST00000566304.5

Conserved Domains (2) summary

cd06562
Location:178 → 522

GH20_HexA_HexB-like; Beta-N-acetylhexosaminidases catalyze the removal of beta-1,4-linked N-acetyl-D-hexosamine residues from the non-reducing ends of N-acetyl-beta-D-hexosaminides including N-acetylglucosides and N-acetylgalactosides. The hexA and hexB genes encode the ...

pfam14845
Location:23 → 156

Glycohydro_20b2; beta-acetyl hexosaminidase like

RNA

NR_134869.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate internal splice site compared to variant 1 and its 3' terminal exon extends past a splice site that is used in variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC009690, AK296528, AW088671, BC018927, DC356933

Related

ENST00000567027.6