HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
HEXA
hexosaminidase subunit alpha
Chromosome 15 Β· 15q23
NCBI Gene: 3073Ensembl: ENSG00000213614.11HGNC: HGNC:4878UniProt: A0A0S2Z3W3
164PubMed Papers
21Diseases
0Drugs
329Pathogenic Variants
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
GO:0005615acetylglucosaminyltransferase activityprotein heterodimerization activitybeta-N-acetylhexosaminidase activityTay-Sachs diseasegenetic disorderTay-Sachs disease, B1 variantTay-Sachs disease AB variant
✦AI Summary

HEXA encodes the alpha subunit of hexosaminidase A (HexA), a lysosomal enzyme that hydrolyzes N-acetyl-D-hexosamine residues from glycoconjugates, including glycoproteins, neutral glycolipids, and mucopolysaccharides 1234. The HexA isozyme specifically catalyzes GM2 ganglioside degradation in conjunction with the GM2A cofactor, a function unique among hexosaminidase isoforms 234. HEXA mutations cause Tay-Sachs disease (TSD), a lysosomal storage disorder characterized by GM2 ganglioside accumulation in neural cells 5. Both infantile-onset and late-onset TSD variants result from HEXA deficiency, leading to progressive neurological decline and reduced lifespan 67. Recent therapeutic approaches include AAV-mediated gene therapy targeting CNS delivery, which has demonstrated disease stabilization and extended survival in early human trials 6. Genome editing strategies, including prime editing and base editing, show promise for correcting pathogenic HEXA mutations with minimal off-target effects 87. These emerging treatments represent significant advances toward clinical intervention for this previously untreatable lysosomal storage disorder.

Sources cited
1
HEXA hydrolyzes N-acetyl-D-hexosamine from glycoconjugates and sulfated glycans
PMID: 11707436
2
HEXA isozyme A specifically degrades GM2 gangliosides with GM2A cofactor
PMID: 8123671
3
HEXA isozyme A required for GM2 ganglioside degradation
PMID: 8672428
4
HEXA isozyme A responsible for GM2 ganglioside degradation
PMID: 9694901
5
HEXA mutations cause Tay-Sachs disease with GM2 ganglioside accumulation
PMID: 11339652
6
AAV gene therapy for infantile TSD shows safety and proof-of-concept with CSF HexA activity restoration
PMID: 35145305
7
Prime editing can correct HEXA deletion mutations causing Tay-Sachs disease
PMID: 31634902
8
Base editing corrects HEXA c.805G>A mutation, extends lifespan and reduces GM2 ganglioside in LOTS mice
PMID: 40526437
Disease Associationsβ“˜21
Tay-Sachs diseaseOpen Targets
0.86Strong
genetic disorderOpen Targets
0.54Moderate
Tay-Sachs disease, B1 variantOpen Targets
0.47Moderate
GM2-gangliosidosis, AB variantOpen Targets
0.46Moderate
Tay-Sachs disease AB variantOpen Targets
0.46Moderate
Tay-Sachs disease, b variant, juvenile formOpen Targets
0.45Moderate
GM2 gangliosidosisOpen Targets
0.37Weak
GM1 gangliosidosisOpen Targets
0.37Weak
Tay-Sachs disease, B variant, adult formOpen Targets
0.37Weak
Tay-Sachs disease, b variant, infantile formOpen Targets
0.37Weak
Global developmental delayOpen Targets
0.34Weak
GM2-ganglioside accumulationOpen Targets
0.34Weak
Hearing impairmentOpen Targets
0.27Weak
leukodystrophyOpen Targets
0.27Weak
SeizureOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.22Weak
coronary artery diseaseOpen Targets
0.15Weak
Intellectual disabilityOpen Targets
0.11Weak
Neurodevelopmental abnormalityOpen Targets
0.11Weak
glioblastoma multiformeOpen Targets
0.08Suggestive
GM2-gangliosidosis 1UniProt
Pathogenic Variants329
NM_000520.6(HEXA):c.1454G>A (p.Trp485Ter)Pathogenic
Tay-Sachs disease
β˜…β˜…β˜†β˜†2026β†’ Residue 485
NM_000520.6(HEXA):c.533G>A (p.Arg178His)Pathogenic
|Tay-Sachs disease, B1 variant|not provided|Tay-Sachs disease|Inborn genetic diseases|HEXA-related disorder|Global developmental delay
β˜…β˜…β˜†β˜†2026β†’ Residue 178
NM_000520.6(HEXA):c.459+5G>APathogenic
Tay-Sachs disease|not provided
β˜…β˜…β˜†β˜†2026
NM_000520.6(HEXA):c.508C>T (p.Arg170Trp)Pathogenic
Tay-Sachs disease|Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 170
NM_000520.6(HEXA):c.1098T>G (p.Tyr366Ter)Pathogenic
Tay-Sachs disease
β˜…β˜…β˜†β˜†2026β†’ Residue 366
NM_000520.6(HEXA):c.233G>A (p.Trp78Ter)Pathogenic
not provided|Tay-Sachs disease
β˜…β˜…β˜†β˜†2026β†’ Residue 78
NM_000520.6(HEXA):c.805G>A (p.Gly269Ser)Pathogenic
Gm2-gangliosidosis, adult|Tay-Sachs disease|not provided|Inborn genetic diseases|HEXA-related disorder|Familial cancer of breast
β˜…β˜…β˜†β˜†2026β†’ Residue 269
NM_000520.6(HEXA):c.1496G>A (p.Arg499His)Pathogenic
GM2-GANGLIOSIDOSIS, JUVENILE|Inborn genetic diseases|Tay-Sachs disease|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 499
NM_000520.6(HEXA):c.460-1G>TPathogenic
Tay-Sachs disease|not provided
β˜…β˜…β˜†β˜†2026
NM_000520.6(HEXA):c.964G>T (p.Asp322Tyr)Pathogenic
Tay-Sachs disease
β˜…β˜…β˜†β˜†2026β†’ Residue 322
NM_000520.6(HEXA):c.1260G>C (p.Trp420Cys)Pathogenic
Tay-Sachs disease|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 420
NM_000520.6(HEXA):c.1274_1277dup (p.Tyr427fs)Pathogenic
Tay-Sachs disease|not provided|Inborn genetic diseases|Tay-Sachs disease, variant AB;Tay-Sachs disease|Intellectual disability|HEXA-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 427
NM_000520.6(HEXA):c.340G>A (p.Glu114Lys)Pathogenic
Tay-Sachs disease
β˜…β˜…β˜†β˜†2026β†’ Residue 114
NM_000520.6(HEXA):c.346+1G>TPathogenic
Tay-Sachs disease|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026
NM_000520.6(HEXA):c.1393G>A (p.Asp465Asn)Likely pathogenic
Tay-Sachs disease|not provided|Inborn genetic diseases|HEXA-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 465
NM_000520.6(HEXA):c.1073+1G>APathogenic
Tay-Sachs disease|not provided|Clear cell carcinoma of kidney|Thyroid cancer, nonmedullary, 1|Lung cancer|Acute myeloid leukemia|Familial cancer of breast|Inborn genetic diseases|HEXA-related disorder
β˜…β˜…β˜†β˜†2026
NM_000520.6(HEXA):c.139C>T (p.Gln47Ter)Pathogenic
Tay-Sachs disease
β˜…β˜…β˜†β˜†2026β†’ Residue 47
NM_000520.6(HEXA):c.1421+1G>CPathogenic
Tay-Sachs disease|not provided|Sarcoma
β˜…β˜…β˜†β˜†2026
NM_000520.6(HEXA):c.1177C>T (p.Arg393Ter)Pathogenic
Tay-Sachs disease|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 393
NM_000520.6(HEXA):c.535C>T (p.His179Tyr)Pathogenic
Tay-Sachs disease
β˜…β˜…β˜†β˜†2026β†’ Residue 179
View on ClinVar β†—
Related Genes
CHIT1Protein interaction100%GM2AProtein interaction100%A4GALTProtein interaction95%NAGAProtein interaction94%GLAProtein interaction94%GNSProtein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
70%
Ovary
58%
Heart
52%
Liver
49%
Brain
36%
Gene Interaction Network
Click a node to explore
HEXACHIT1GM2AA4GALTNAGAGLAGNS
PROTEIN STRUCTURE
Preparing viewer…
PDB2GJX Β· 2.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.95LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.73 [0.57–0.95]
RankingsWhere HEXA stands among ~20K protein-coding genes
  • #2,730of 20,598
    Most Researched164 Β· top quartile
  • #181of 5,498
    Most Pathogenic Variants329 Β· top 5%
  • #8,845of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedHEXA
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Search-and-replace genome editing without double-strand breaks or donor DNA.
PMID: 31634902
Nature Β· 2019
1.00
2
Repeat expansion diseases.
PMID: 29325606
Handb Clin Neurol Β· 2018
0.90
3
AAV gene therapy for Tay-Sachs disease.
PMID: 35145305
Nat Med Β· 2022
0.80
4
Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses.
PMID: 39929976
Nat Microbiol Β· 2025
0.70
5
Synthetic Heparanase Inhibitors Can Prevent Herpes Simplex Viral Spread.
PMID: 37555536
Angew Chem Int Ed Engl Β· 2023
0.68