HEXB

hexosaminidase subunit beta, the group of Hexosaminidases

Basic information

Region (hg38): 5:74640022-74722647

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 (Definitive), mode of inheritance: AR
• Sandhoff disease (Strong), 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 (569 variants)
• not provided (104 variants)
• not specified (34 variants)
• Inborn genetic diseases (24 variants)
• Sandhoff disease, juvenile form (3 variants)
• Sandhoff disease, infantile form (3 variants)
• Sandhoff disease, adult form (2 variants)
• HEXB POLYMORPHISM (2 variants)
• See cases (1 variants)
• HEXOSAMINIDASE B, HEAT-LABILE POLYMORPHISM (1 variants)
• Hexosaminidase B (paris) (1 variants)
• HEXB-related condition (1 variants)
• Sandhoff disease, chronic (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.

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				157		157
missense	4	16	110	9	4	143
nonsense	14	25				39
start loss						0
frameshift	43	24				67
inframe indel	1		12			13
splice donor/acceptor (+/-2bp)	2	15				17
splice region		2	12	34	2	50
non coding	1	2	13	75	32	123
Total	65	82	135	241	36

Highest pathogenic variant AF is 0.0000331

Variants in HEXB

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

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

Position	Type	Phenotype	Significance	ClinVar
5-74684878-A-T			Benign (Jun 19, 2018)
5-74684879-T-G			Benign (Jun 19, 2018)
5-74684974-G-C			Benign (Jun 19, 2018)
5-74685086-G-A		Sandhoff disease	Benign (Jul 05, 2018)
5-74685135-C-T		Sandhoff disease	Benign (Feb 01, 2024)
5-74685138-GC-G		Sandhoff disease	Benign (Feb 01, 2024)
5-74685139-C-T		Sandhoff disease	Uncertain significance (Feb 06, 2022)
5-74685198-G-A		Sandhoff disease	Uncertain significance (Jan 13, 2018)
5-74685199-G-A		Sandhoff disease	Uncertain significance (Mar 23, 2018)
5-74685209-C-A		Sandhoff disease	Uncertain significance (Jan 13, 2018)
5-74685247-G-A		Sandhoff disease	Uncertain significance (Jan 12, 2018)
5-74685267-C-T		Sandhoff disease	Likely benign (Jul 13, 2022)
5-74685269-G-T		Sandhoff disease	Likely benign (Jul 14, 2023)
5-74685272-C-T		Sandhoff disease	Likely benign (Aug 08, 2022)
5-74685274-G-A		Sandhoff disease	Uncertain significance (Aug 15, 2020)
5-74685275-G-T		Sandhoff disease	Likely benign (Jan 02, 2024)
5-74685276-C-T		Sandhoff disease	Likely benign (Dec 20, 2022)
5-74685280-G-A		Sandhoff disease	Uncertain significance (Feb 24, 2022)
5-74685281-G-A		Sandhoff disease	Likely benign (Sep 08, 2023)
5-74685292-C-T		Sandhoff disease	Uncertain significance (May 15, 2022)
5-74685293-G-T		Sandhoff disease	Likely benign (Jun 27, 2023)
5-74685294-C-T		Inborn genetic diseases	Uncertain significance (Jan 06, 2023)
5-74685296-C-T		Sandhoff disease	Likely benign (Aug 10, 2023)
5-74685299-G-A		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
5-74685302-G-A		Sandhoff disease	Likely benign (Nov 09, 2023)

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
3.49e-10	0.922	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

Haploinsufficiency Scores

• pHI: 0.205
• hipred: N
• hipred_score: 0.332
• ghis: 0.399

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

Mouse Genome Informatics

• Gene name: Hexb
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary 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; 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; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

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