HEXA

hexosaminidase subunit alpha, the group of Hexosaminidases

Basic information

Region (hg38): 15:72340924-72376420

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tay-Sachs disease; GM2-gangliosidosis; Hexosaminidase A deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	5793973; 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 (103 variants)
• not provided (15 variants)
• Inborn genetic diseases (2 variants)
• HEXA-related disorder (2 variants)
• Tay-Sachs disease, B1 variant (1 variants)
• Intellectual disability (1 variants)
• GM2-ganglioside accumulation (1 variants)
• Gm2-gangliosidosis, juvenile (1 variants)
• Tay-Sachs disease;Tay-Sachs disease, variant AB (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. These statistics are base on transcript: . Only rare variants are included in the table.

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	1	3	255	1	261
missense	12	35	303	6	1	357
nonsense	26	40				66
start loss	5	1	1			7
frameshift	45	28	2			75
splice donor/acceptor (+/-2bp)	14	21	1			36
Total	103	126	310	261	2

Highest pathogenic variant AF is 0.000440343

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HEXA	protein_coding	protein_coding	ENST00000268097	14	33043

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.34e-11	0.774	125392	0	356	125748	0.00142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.409	297	278	1.07	0.0000155	3447
Missense in Polyphen		129	141.45	0.91201		1695
Synonymous	0.325	103	107	0.960	0.00000572	1032
Loss of Function	1.68	22	32.3	0.681	0.00000179	350

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00120	0.00114
Ashkenazi Jewish	0.0155	0.0156
East Asian	0.000272	0.000272
Finnish	0.000323	0.000323
European (Non-Finnish)	0.00123	0.00123
Middle Eastern	0.000272	0.000272
South Asian	0.000294	0.000294
Other	0.00196	0.00196

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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