HEXA

Protein identityUniProt · HPA

UniProt accession

P06865

Gene

HEXA

Ensembl

ENSG00000213614

Chromosome

15

Canonical length

529 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles,Cytosol

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

529 residues, UniProt reviewed canonical sequence.

>P06865|HEXA
     1  MTSSRLWFSL LLAAAFAGRA TALWPWPQNF QTSDQRYVLY PNNFQFQYDV SSAAQPGCSV
    61  LDEAFQRYRD LLFGSGSWPR PYLTGKRHTL EKNVLVVSVV TPGCNQLPTL ESVENYTLTI
   121  NDDQCLLLSE TVWGALRGLE TFSQLVWKSA EGTFFINKTE IEDFPRFPHR GLLLDTSRHY
   181  LPLSSILDTL DVMAYNKLNV FHWHLVDDPS FPYESFTFPE LMRKGSYNPV THIYTAQDVK
   241  EVIEYARLRG IRVLAEFDTP GHTLSWGPGI PGLLTPCYSG SEPSGTFGPV NPSLNNTYEF
   301  MSTFFLEVSS VFPDFYLHLG GDEVDFTCWK SNPEIQDFMR KKGFGEDFKQ LESFYIQTLL
   361  DIVSSYGKGY VVWQEVFDNK VKIQPDTIIQ VWREDIPVNY MKELELVTKA GFRALLSAPW
   421  YLNRISYGPD WKDFYIVEPL AFEGTPEQKA LVIGGEACMW GEYVDNTNLV PRLWPRAGAV
   481  AERLWSNKLT SDLTFAYERL SHFRCELLRR GVQAQPLNVG FCEQEFEQT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HEXA 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)

0.23

Highest tissue expression

145 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HEXA.

Disease | AllUniProt

Conditions HEXA is implicated in, by any mechanism.

• GM2-gangliosidosis 1 (GM2G1) MIM:272800

Disease | GeneticClinVar

330 pathogenic / likely-pathogenic of 1,349 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Tay-Sachs disease
• Inborn genetic diseases
• HEXA-related disorder
• Tay-Sachs disease, B1 variant
• Familial cancer of breast

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)

0.97

gnomAD pLI

0

gnomAD missense Z

-0.41

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult walking behavior
• carbohydrate metabolic process
• cell morphogenesis involved in neuron differentiation
• dermatan sulfate proteoglycan catabolic process
• ganglioside catabolic process
• glycosaminoglycan biosynthetic process
• glycosaminoglycan metabolic process
• hyaluronan catabolic process
• lipid storage
• lysosome organization
• myelination
• N-glycan processing
• neuromuscular process controlling balance
• neuromuscular process controlling posture
• sensory perception of sound
• skeletal system development

Molecular functions

• acetylglucosaminyltransferase activity
• beta-N-acetylhexosaminidase activity
• protein heterodimerization activity

Cellular components

• azurophil granule
• beta-N-acetylhexosaminidase complex
• cytosol
• extracellular exosome
• extracellular space
• lysosomal lumen
• lysosome
• membrane

Protein domainsUniProt · Pfam · InterPro

• Beta-hexosaminidase, catalytic domain
• Glycoside hydrolase superfamily
• Beta-hexosaminidase
• Beta-hexosaminidase-like, domain 2
• Beta-hexosaminidase, eukaryotic type, N-terminal
• Glycosyl hydrolase family 20, catalytic domain
• beta-acetyl hexosaminidase like

KeywordsUniProt

• Disulfide bond
• Gangliosidosis
• Glycoprotein
• Glycosidase
• Hydrolase
• Lipid metabolism
• Lysosome
• Neurodegeneration
• Signal
• Zymogen

InteractionsUniProt · HPA

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

• HEXB