HEXB

hexosaminidase subunit beta, the group of Hexosaminidases

Basic information

Region (hg38): 5:74640023-74722647

Links

ENSG00000049860

∙ NCBI:3074 ∙ OMIM:606873 ∙ HGNC:4879 ∙ Uniprot:P07686 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Sandhoff disease (Definitive), mode of inheritance: AR
Sandhoff disease (Definitive), mode of inheritance: AR
Sandhoff disease (Strong), mode of inheritance: AR
Sandhoff disease (Strong), mode of inheritance: AR
Sandhoff disease (Definitive), mode of inheritance: AR
Sandhoff disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sandhoff disease	AR	General	Substrate reduction therapy has been described as potentially beneficial; 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	5651108; 571983; 3017984; 2948136; 8357844; 15956171; 18758829; 19898952; 20798201; 21150067; 22789865; 22848519; 23046579; 23113155

ClinVar

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

Sandhoff_disease (754 variants)
not_provided (99 variants)
Inborn_genetic_diseases (76 variants)
not_specified (33 variants)
HEXB-related_disorder (10 variants)
Sandhoff_disease,_infantile_form (4 variants)
Sandhoff_disease,_juvenile_form (3 variants)
See_cases (3 variants)
Sandhoff_disease,_adult_form (3 variants)
HEXOSAMINIDASE_B,_HEAT-LABILE_POLYMORPHISM (1 variants)
Sandhoff_disease,_chronic (1 variants)
Hexosaminidase_B_(Paris) (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HEXB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000521.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	1 clinvar	10 clinvar	210 clinvar		222
missense	6 clinvar	31 clinvar	191 clinvar	12 clinvar	1 clinvar	241
nonsense	24 clinvar	24 clinvar	1 clinvar			49
start loss						0
frameshift	61 clinvar	38 clinvar	2 clinvar			101
splice donor/acceptor (+/-2bp)	3 clinvar	19 clinvar	4 clinvar	1 clinvar		27
Total	95	113	208	223	1

Highest pathogenic variant AF is 0.000776943

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HEXB	protein_coding	protein_coding	ENST00000261416	14	82625

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125661	0	87	125748	0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.648	260	291	0.893	0.0000142	3609
Missense in Polyphen		73	90.806	0.80391		1109
Synonymous	-0.258	111	108	1.03	0.00000515	1060
Loss of Function	1.93	20	31.7	0.630	0.00000165	368

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00118	0.00118
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000961	0.0000924
European (Non-Finnish)	0.000256	0.000255
Middle Eastern	0.0000544	0.0000544
South Asian	0.000524	0.000523
Other	0.000655	0.000652

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.;
Disease: DISEASE: GM2-gangliosidosis 2 (GM2G2) [MIM:268800]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. Clinically indistinguishable from GM2-gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula. {ECO:0000269|PubMed:1531140, ECO:0000269|PubMed:1720305, ECO:0000269|PubMed:7557963, ECO:0000269|PubMed:7626071, ECO:0000269|PubMed:7633435, ECO:0000269|PubMed:8357844, ECO:0000269|PubMed:8950198, ECO:0000269|PubMed:9401004, ECO:0000269|PubMed:9694901, ECO:0000269|PubMed:9856491}. 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);Neutrophil degranulation;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;Innate Immune System;Immune System;Metabolism;dermatan sulfate degradation (metazoa);Aminosugars metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

pRec: 0.0805

Intolerance Scores

loftool: 0.371
rvis_EVS: 0.95
rvis_percentile_EVS: 90.06

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.667

Gene Damage Prediction

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

Zebrafish Information Network

Gene name: hexb
Affected structure: intersegmental vessel
Phenotype tag: abnormal
Phenotype quality: morphology

Gene ontology

Biological process: skeletal system development;glycosphingolipid metabolic process;ganglioside catabolic process;cellular calcium ion homeostasis;lysosome organization;penetration of zona pellucida;sensory perception of sound;locomotory behavior;male courtship behavior;regulation of cell shape;phospholipid biosynthetic process;oligosaccharide catabolic process;lipid storage;chondroitin sulfate catabolic process;hyaluronan catabolic process;keratan sulfate catabolic process;myelination;neutrophil degranulation;astrocyte cell migration;cellular protein metabolic process;positive regulation of transcription by RNA polymerase II;oogenesis;neuromuscular process controlling balance
Cellular component: acrosomal vesicle;extracellular region;membrane;azurophil granule lumen;azurophil granule;lysosomal lumen;extracellular exosome
Molecular function: beta-N-acetylhexosaminidase activity;protein binding;acetylglucosaminyltransferase activity;protein homodimerization activity;protein heterodimerization activity;N-acetyl-beta-D-galactosaminidase activity