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GeneBe

HEXA

hexosaminidase subunit alpha, the group of Hexosaminidases

Basic information

Region (hg38): 15:72340923-72376420

Links

ENSG00000213614 ∙ NCBI:3073 ∙ OMIM:606869 ∙ HGNC:4878 ∙ Uniprot:P06865 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Tay-Sachs disease (Definitive), mode of inheritance: AR
  • Tay-Sachs disease (Definitive), mode of inheritance: AR
  • Tay-Sachs disease (Strong), mode of inheritance: AR
  • Tay-Sachs disease (Strong), mode of inheritance: AR
  • Tay-Sachs disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Tay-Sachs disease; GM2-gangliosidosis; Hexosaminidase A deficiencyARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingBiochemical; Neurologic; Ophthalmologic5793973; 175770; 3375249; 2848800; 2140574; 2220809; 2824459; 2137287; 9090523; 15557512; 15714079; 15108204; 15956171; 20301397; 21937992; 21967858; 22441121; 22723944; 22789865

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HEXA gene.

  • Tay-Sachs disease (943 variants)
  • not provided (119 variants)
  • Inborn genetic diseases (51 variants)
  • not specified (43 variants)
  • Gm2-gangliosidosis, late onset (3 variants)
  • Tay-Sachs disease, B1 variant (3 variants)
  • Tay-Sachs disease;Tay-Sachs disease, variant AB (3 variants)
  • Intellectual disability (2 variants)
  • Gm2-gangliosidosis, chronic (2 variants)
  • Gm2-gangliosidosis, juvenile (2 variants)
  • Gm2-gangliosidosis, subacute (2 variants)
  • Global developmental delay (1 variants)
  • Hexa, dn allele (1 variants)
  • Tay-sachs disease, juvenile (1 variants)
  • Beta-hexosaminidase a, pseudodeficiency of (1 variants)
  • GM2-ganglioside accumulation (1 variants)
  • - (1 variants)
  • Tay-sachs disease, juvenile/adult (1 variants)
  • HEXA-related condition (1 variants)
  • Gm2-gangliosidosis, variant b1 (1 variants)
  • Gm2-gangliosidosis, adult (1 variants)
  • Gm2-gangliosidosis, adult-onset (1 variants)
  • Leukodystrophy;Seizure;Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HEXA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
1
clinvar
3
clinvar
222
clinvar
1
clinvar
 228
missense
11
clinvar
32
clinvar
288
clinvar
5
clinvar
1
clinvar
 337
nonsense
23
clinvar
39
clinvar
 62
start loss
4
clinvar
1
clinvar
1
clinvar
 6
frameshift
40
clinvar
27
clinvar
2
clinvar
 69
inframe indel
3
clinvar
7
clinvar
 10
splice donor/acceptor (+/-2bp)
12
clinvar
20
clinvar
1
clinvar
 33
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
2
2
16
42
 62
non coding
?
    UTR, intron and other, non coding variants
1
clinvar
12
clinvar
108
clinvar
20
clinvar
 141
Total 92 123 314 335 22

Highest pathogenic variant AF is 0.000440

Variants in HEXA

This is a list of pathogenic ClinVar variants found in the HEXA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
15-72343447-T-C Tay-Sachs disease Likely benign (Jun 14, 2016)317032
15-72343488-A-C Tay-Sachs disease Benign (Jun 14, 2016)317033
15-72343502-C-T Tay-Sachs disease Uncertain significance (Jun 14, 2016)317034
15-72343562-C-T Tay-Sachs disease Benign (Jun 14, 2016)317035
15-72343641-G-A Tay-Sachs disease Uncertain significance (Jun 14, 2016)317036
15-72343722-G-C Tay-Sachs disease Uncertain significance (Jun 14, 2016)317037
15-72343877-A-G Tay-Sachs disease Uncertain significance (Jun 14, 2016)317038
15-72344001-C-T Tay-Sachs disease Uncertain significance (Jun 14, 2016)317039
15-72344065-G-A Tay-Sachs disease Uncertain significance (Jul 10, 2017)317040
15-72344080-G-A Tay-Sachs disease Likely benign (Nov 09, 2023)1919129
15-72344088-CA-C Tay-Sachs disease Uncertain significance (Dec 29, 2016)550258
15-72344089-A-G Tay-Sachs disease Likely benign (Sep 25, 2021)1604217
15-72344093-T-C Tay-Sachs disease Uncertain significance (May 09, 2022)1985845
15-72344095-C-T Tay-Sachs disease Likely benign (Sep 29, 2023)696182
15-72344095-CT-C Tay-Sachs disease Uncertain significance (Mar 14, 2018)557264
15-72344096-T-G Tay-Sachs disease Uncertain significance (Jun 06, 2021)1359380
15-72344098-CT-C Tay-Sachs disease Uncertain significance (Jul 11, 2021)1359999
15-72344104-G-A Tay-Sachs disease Likely benign (Dec 07, 2023)2018082
15-72344108-C-T Inborn genetic diseases Likely pathogenic (Nov 21, 2014)1775212
15-72344110-T-C Tay-Sachs disease Likely benign (Jul 09, 2023)1118732
15-72344111-A-G Tay-Sachs disease Uncertain significance (May 21, 2022)2419972
15-72344111-A-T Tay-Sachs disease Uncertain significance (Jul 14, 2021)989841
15-72344113-A-G Tay-Sachs disease Likely benign (May 22, 2023)1110941
15-72344117-A-AG Tay-Sachs disease Pathogenic/Likely pathogenic (May 15, 2023)528047
15-72344118-G-C Uncertain significance (Apr 01, 2019)807284

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
HEXAprotein_codingprotein_codingENST00000268097 1433043
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.34e-110.77412539203561257480.00142
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.4092972781.070.00001553447
Missense in Polyphen129141.450.912011695
Synonymous0.3251031070.9600.000005721032
Loss of Function1.682232.30.6810.00000179350

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001200.00114
Ashkenazi Jewish0.01550.0156
East Asian0.0002720.000272
Finnish0.0003230.000323
European (Non-Finnish)0.001230.00123
Middle Eastern0.0002720.000272
South Asian0.0002940.000294
Other0.001960.00196

dbNSFP

Source: dbNSFP

Function
FUNCTION: Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues. The form B is active against certain oligosaccharides. The form S has no measurable activity.;
Disease
DISEASE: GM2-gangliosidosis 1 (GM2G1) [MIM:272800]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. It is characterized by GM2 gangliosides accumulation in the absence of HEXA activity, leading to neurodegeneration and, in the infantile form, death in early childhood. It exists in several forms: infantile (most common and most severe), juvenile and adult (late-onset). {ECO:0000269|PubMed:1301189, ECO:0000269|PubMed:1301190, ECO:0000269|PubMed:1302612, ECO:0000269|PubMed:14566483, ECO:0000269|PubMed:1532289, ECO:0000269|PubMed:1837283, ECO:0000269|PubMed:2140574, ECO:0000269|PubMed:2144098, ECO:0000269|PubMed:22723944, ECO:0000269|PubMed:2522679, ECO:0000269|PubMed:27682588, ECO:0000269|PubMed:2970528, ECO:0000269|PubMed:7717398, ECO:0000269|PubMed:7837766, ECO:0000269|PubMed:7898712, ECO:0000269|PubMed:7951261, ECO:0000269|PubMed:8445615, ECO:0000269|PubMed:8490625, ECO:0000269|PubMed:8581357, ECO:0000269|PubMed:8757036, ECO:0000269|PubMed:9150157, ECO:0000269|PubMed:9338583, ECO:0000269|PubMed:9375850, ECO:0000269|PubMed:9401008, ECO:0000269|PubMed:9603435}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Glycosphingolipid biosynthesis - ganglio series - Homo sapiens (human);Lysosome - Homo sapiens (human);Other glycan degradation - Homo sapiens (human);Glycosphingolipid biosynthesis - globo and isoglobo series - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Sialuria or French Type Sialuria;Sialuria or French Type Sialuria;Amino Sugar Metabolism;G(M2)-Gangliosidosis: Variant B, Tay-sachs disease;Tay-Sachs Disease;Salla Disease/Infantile Sialic Acid Storage Disease;Degradation pathway of sphingolipids, including diseases;Hyaluronan uptake and degradation;Hyaluronan metabolism;Metabolism of carbohydrates;Keratan sulfate degradation;Keratan sulfate/keratin metabolism;Metabolism of lipids;CS/DS degradation;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;chondroitin sulfate degradation (metazoa);Glycosphingolipid biosynthesis - ganglioseries;Glycosphingolipid biosynthesis - globoseries;Metabolism;dermatan sulfate degradation (metazoa);Aminosugars metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

pRec
0.595

Intolerance Scores

loftool
0.170
rvis_EVS
-0.33
rvis_percentile_EVS
30.7

Haploinsufficiency Scores

pHI
0.111
hipred
N
hipred_score
0.285
ghis
0.585

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Hexa
Phenotype
growth/size/body region phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype;

Zebrafish Information Network

Gene name
hexa
Affected structure
macrophage
Phenotype tag
abnormal
Phenotype quality
morphology

Gene ontology

Biological process
carbohydrate metabolic process;glycosaminoglycan biosynthetic process;glycosphingolipid metabolic process;chondroitin sulfate catabolic process;hyaluronan catabolic process;keratan sulfate catabolic process
Cellular component
membrane;azurophil granule;lysosomal lumen;extracellular exosome
Molecular function
beta-N-acetylhexosaminidase activity;protein binding;acetylglucosaminyltransferase activity;protein heterodimerization activity;N-acetyl-beta-D-galactosaminidase activity