HEXB (hexosaminidase subunit beta)

Gene

• Entrez ID: 3074
• Gene name: Hexosaminidase subunit beta
• Gene symbol: HEXB
• Synonyms: ENC-1AS, HEL-248, HEL-S-111
• Chromosome: 5
• Chromosome location: 5q13.3
• Summary: Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs820878	T>C	Pathogenic, benign	Coding sequence variant, intron variant, missense variant
rs5030731	G>A,C	Pathogenic-likely-pathogenic, pathogenic	Intron variant
rs28942073	C>T	Pathogenic	Coding sequence variant, missense variant
rs121907982	A>C	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs121907983	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs121907985	C>T	Pathogenic	Coding sequence variant, missense variant
rs121907986	C>T	Pathogenic	Stop gained, coding sequence variant
rs138914144	C>T	Pathogenic	Stop gained, coding sequence variant
rs147155126	C>T	Conflicting-interpretations-of-pathogenicity, benign-likely-benign	Coding sequence variant, intron variant, missense variant
rs201580118	G>A,C	Conflicting-interpretations-of-pathogenicity	Intron variant
rs373979283	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs398123443	G>-	Pathogenic	Intron variant, coding sequence variant, frameshift variant
rs398123444	AAGTTGTT>-	Pathogenic, uncertain-significance	Intron variant, splice donor variant
rs398123445	CAAAG>-	Pathogenic	Frameshift variant, coding sequence variant
rs398123446	A>G	Likely-pathogenic, pathogenic	Splice acceptor variant
rs398123447	G>T	Likely-pathogenic	Coding sequence variant, missense variant
rs398123450	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs573447174	T>C,G	Likely-pathogenic, pathogenic	Stop gained, synonymous variant, coding sequence variant, 5 prime UTR variant
rs727503959	G>A,C	Likely-pathogenic	Intron variant
rs753823903	C>T	Pathogenic, likely-pathogenic	Stop gained, coding sequence variant, 5 prime UTR variant
rs761117459	G>A,C	Pathogenic	Stop gained, missense variant, coding sequence variant, 5 prime UTR variant
rs761197472	G>A,C,T	Pathogenic-likely-pathogenic, pathogenic, benign	Splice donor variant
rs762892362	G>A	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs768438206	T>-	Pathogenic-likely-pathogenic	Coding sequence variant, frameshift variant
rs771103635	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs771973471	G>-,GG	Pathogenic	Coding sequence variant, intron variant, frameshift variant
rs776476415	TGAG>-	Pathogenic, likely-pathogenic	Coding sequence variant, frameshift variant
rs779328596	AG>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs794727049	T>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs794727091	GA>-	Likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant
rs797044644	->CAAGTGCTGTTGG	Pathogenic	Coding sequence variant, frameshift variant
rs886039499	C>-	Likely-pathogenic, pathogenic	Coding sequence variant, intron variant, frameshift variant
rs892920643	G>A	Conflicting-interpretations-of-pathogenicity	Intron variant
rs967720287	G>A,C	Likely-pathogenic	Splice acceptor variant
rs1007338250	C>G,T	Pathogenic	Coding sequence variant, missense variant, stop gained, intron variant
rs1057518237	->ACCC	Pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1060499701	G>A,C,T	Pathogenic	Missense variant, coding sequence variant, intron variant
rs1114167287	G>A	Pathogenic	Stop gained, coding sequence variant, intron variant
rs1309123671	G>A	Likely-pathogenic	Coding sequence variant, synonymous variant
rs1453919511	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1554034423	T>-	Likely-pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1554034434	C>T	Pathogenic	Coding sequence variant, stop gained, intron variant
rs1554034447	G>-	Likely-pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1554034449	G>-	Likely-pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1554034452	C>A	Likely-pathogenic	Coding sequence variant, stop gained, intron variant
rs1554034505	G>A	Likely-pathogenic	Intron variant, splice donor variant
rs1554035308	G>T	Likely-pathogenic	Splice acceptor variant
rs1554036523	T>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1554036638	G>T	Likely-pathogenic	Splice acceptor variant
rs1554036943	C>G	Likely-pathogenic	Coding sequence variant, stop gained
rs1554037076	ATTTTAATTTAGG>-	Likely-pathogenic	Coding sequence variant, intron variant, splice acceptor variant
rs1554037120	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1554037129	->GAGA	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1579950499	T>G	Pathogenic	Stop gained, coding sequence variant
rs1579952143	->T	Pathogenic	Frameshift variant, coding sequence variant
rs1580377105	A>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs1580377261	GCCCCT>CCCCC	Pathogenic	Intron variant, frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030011	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	IEA
GO:0001669	Component	Acrosomal vesicle	IEA
GO:0004563	Function	Beta-N-acetylhexosaminidase activity	IDA	8123671, 8672428
GO:0005515	Function	Protein binding	IPI	16698036, 28514442, 32296183, 32814053
GO:0005576	Component	Extracellular region	TAS
GO:0006687	Process	Glycosphingolipid metabolic process	TAS
GO:0006689	Process	Ganglioside catabolic process	IDA	8123671, 8672428
GO:0006874	Process	Cellular calcium ion homeostasis	IEA
GO:0007040	Process	Lysosome organization	IEA
GO:0007341	Process	Penetration of zona pellucida	IEA
GO:0007605	Process	Sensory perception of sound	IEA
GO:0007626	Process	Locomotory behavior	IEA
GO:0008049	Process	Male courtship behavior	IEA
GO:0008360	Process	Regulation of cell shape	IEA
GO:0008375	Function	Acetylglucosaminyltransferase activity	IDA	25645918
GO:0008654	Process	Phospholipid biosynthetic process	IEA
GO:0009313	Process	Oligosaccharide catabolic process	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0019915	Process	Lipid storage	IEA
GO:0030207	Process	Chondroitin sulfate catabolic process	TAS
GO:0030214	Process	Hyaluronan catabolic process	TAS
GO:0035578	Component	Azurophil granule lumen	TAS
GO:0042340	Process	Keratan sulfate catabolic process	TAS
GO:0042552	Process	Myelination	IEA
GO:0042582	Component	Azurophil granule	IDA	25645918
GO:0042802	Function	Identical protein binding	IDA	6230359
GO:0043202	Component	Lysosomal lumen	TAS
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043615	Process	Astrocyte cell migration	IEA
GO:0044267	Process	Cellular protein metabolic process	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048477	Process	Oogenesis	IEA
GO:0050885	Process	Neuromuscular process controlling balance	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0102148	Function	N-acetyl-beta-D-galactosaminidase activity	IEA

Other IDs

• MIM: 606873
• HGNC: 4879
• e!Ensembl: ENSG00000049860

Protein

• UniProt ID: P07686
• Protein name: Beta-hexosaminidase subunit beta (EC 3.2.1.52) (Beta-N-acetylhexosaminidase subunit beta) (Hexosaminidase subunit B) (Cervical cancer proto-oncogene 7 protein) (HCC-7) (N-acetyl-beta-glucosaminidase subunit beta) [Cleaved into: Beta-hexosaminidase subunit beta chain B; Beta-hexosaminidase subunit beta chain A]
• Protein function: Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides (PubMed:11707436, PubMed:9694901, PubMed:8672428, PubMed:8123671). The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide (PubMed:11707436). Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A (PubMed:9694901, PubMed:8672428, PubMed:8123671). During fertilization is responsible, at least in part, for the zona block to polyspermy. Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and inactivates the sperm galactosyltransferase-binding site, accounting for the block in sperm binding to the zona pellucida (By similarity).
• PDB: 1NOU, 1NOW, 1NP0, 1O7A, 1QBD, 2GJX, 2GK1, 3LMY, 5BRO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF14845	Glycohydro_20b2	56 → 178	beta-acetyl hexosaminidase like	Domain
  PF00728	Glyco_hydro_20	200 → 517	Glycosyl hydrolase family 20, catalytic domain	Domain

• Sequence:

  MELCGLGLPRPPMLLALLLATLLAAMLALLTQVALVVQVAEAARAPSVSAKPGPALWPLP
  LSVKMTPNLLHLAPENFYISHSPNSTAGPSCTLLEEAFRRYHGYIFGFYKWHHEPAEFQA
  KTQVQQLLVSITLQSECDAFPNISSDESYTLLVKEPVAVLKANRVWGALRGLETFSQLVY
  QDSYGTFTINESTIIDSPRFSHRGILIDTSRHYLPVKIILKTLDAMAFNKFNVLHWHIVD
  DQSFPYQSITFPELSNKGSYSLSHVYTPNDVRMVIEYARLRGIRVLPEFDTPGHTLSWGK
  GQKDLLTPCYSRQNKLDSFGPINPTLNTTYSFLTTFFKEISEVFPDQFIHLGGDEVEFKC
  WESNPKIQDFMRQKGFGTDFKKLESFYIQKVLDIIATINKGSIVWQEVFDDKAKLAPGTI
  VEVWKDSAYPEELSRVTASGFPVILSAPWYLDLISYGQDWRKYYKVEPLDFGGTQKQKQL
  FIGGEACLWGEYVDATNLTPRLWPRASAVGERLWSSKDVRDMDDAYDRLTRHRCRMVERG
  IAAQPLYAGYCNHENM

• Sequence length: 556

Pathways

KEGG:

Other glycan degradation
Various types of N-glycan biosynthesis
Amino sugar and nucleotide sugar metabolism
Glycosaminoglycan degradation
Sphingolipid metabolism
Glycosphingolipid biosynthesis - globo and isoglobo series
Glycosphingolipid biosynthesis - ganglio series
Metabolic pathways
Lysosome

Reactome:

Glycosphingolipid metabolism
Keratan sulfate degradation
CS/DS degradation
Hyaluronan uptake and degradation
Defective HEXB causes GM2G2
Neutrophil degranulation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Myoclonic epilepsy	Myoclonic Epilepsy	rs267607103, rs267607104, rs137852778, rs137852781, rs147484110, rs74315442, rs74315443, rs-1, rs121909346, rs121918622, rs121918623, rs121917954, rs121917955, rs1574272192, rs121918624, rs121918625, rs121918628, rs121918629, rs121918630, rs1574061044, rs121918632, rs397514458, rs397514459, rs386833439, rs386833440, rs386833441, rs796943858, rs386833443, rs398122387, rs121917923, rs121917957, rs121917929, rs121917927, rs121917966, rs121917967, rs121917990, rs121917941, rs121917964, rs121917943, rs121917972, rs121917965, rs121917918, rs121917963, rs121917911, rs121917912, rs121917986, rs121917987, rs121917913, rs121917974, rs121917945, rs121917975, rs121917919, rs121917993, rs121917915, rs121917995, rs121917976, rs121917949, rs121917926, rs121917950, rs121917951, rs121917952, rs121917980, rs121917921, rs121917981, rs121917935, rs121917936, rs121917984, rs121917937, rs121917985, rs121917909, rs121917938, rs121917928, rs121918753, rs121918782, rs121918784, rs121918733, rs121918734, rs121918788, rs121918736, rs121917969, rs121918775, rs121918737, rs121918786, rs121918796, rs121918754, rs121918745, rs121918738, rs121918746, rs121918740, rs121918741, rs121918789, rs121918742, rs121918791, rs121918811, rs121917922, rs121918797, rs121918744, rs121918778, rs121918767, rs121918779, rs121918770, rs121918763, rs121918757, rs121918751, rs121918783, rs121918773, rs121918793, rs121918780, rs121918735, rs398123585, rs398123588, rs398123593, rs545986367, rs727504136, rs794726737, rs794726739, rs794726845, rs779614747, rs794726726, rs372098964, rs794726801, rs794726769, rs794726781, rs794726780, rs794726741, rs794726783, rs794726832, rs794726814, rs794726722, rs794726703, rs794726702, rs794726763, rs794726802, rs794726804, rs794726748, rs794726851, rs794726740, rs794726754, rs794726698, rs794726758, rs794726760, rs794726819, rs794726839, rs794726759, rs199727342, rs794726701, rs794726850, rs794726785, rs794726800, rs764037830, rs794726757, rs794726752, rs794726825, rs794726835, rs139300715, rs794726809, rs794726696, rs794726734, rs794726699, rs794726705, rs794726784, rs794726745, rs794726707, rs794726779, rs794726821, rs794726822, rs794726789, rs794726723, rs146878122, rs794726816, rs794726700, rs794726853, rs794726731, rs794726852, rs794726841, rs794726709, rs777939538, rs794726817, rs794726727, rs794726706, rs794726770, rs794726735, rs794726744, rs794726854, rs794726710, rs794726720, rs794726836, rs794726774, rs794726729, rs794726728, rs794726733, rs542420576, rs794726756, rs794726813, rs794726830, rs794726714, rs794726772, rs1696406839, rs794726842, rs794726828, rs794726823, rs794726708, rs794726808, rs794726716, rs121917971, rs794726718, rs794726721, rs794726761, rs794726815, rs794726786, rs794726787, rs794726697, rs794726775, rs794726712, rs794726794, rs794726738, rs794726805, rs767045134, rs794726820, rs794726766, rs794726750, rs794726743, rs794726742, rs794726795, rs794726730, rs794726806, rs794726747, rs794726838, rs794726778, rs794726834, rs794726736, rs794726704, rs794726773, rs794726749, rs794726717, rs794726790, rs794726829, rs794726807, rs794726810, rs121917989, rs794726826, rs794726725, rs794726818, rs794726776, rs794726777, rs794726765, rs794726753, rs794726732, rs794726799, rs794726695, rs794726792, rs794726767, rs794726768, rs794726844, rs794726782, rs794726797, rs794726843, rs794726798, rs794726824, rs794726837, rs794726846, rs794726788, rs794726847, rs794726812, rs794726771, rs794726751, rs773407463, rs794726755, rs794726719, rs794726724, rs794726833, rs794726827, rs1553551314, rs794726840, rs794726849, rs794726764, rs794726803, rs794726831, rs794726711, rs794726793, rs760361423, rs794726796, rs794726762, rs35595680, rs764444350, rs794726848, rs786205214, rs794729200, rs794729207, rs796053029, rs796053014, rs796053010, rs796053004, rs796053001, rs796052973, rs779184118, rs781746113, rs796052961, rs796052957, rs863225037, rs863225036, rs863225035, rs863225034, rs863225033, rs863225032, rs863225030, rs863225038, rs863225031, rs869312670, rs869312684, rs886039430, rs121917959, rs886041980, rs886042528, rs781507889, rs1057517959, rs1057518671, rs1057519533, rs1057519534, rs1057519530, rs1057519531, rs1060502189, rs1064794766, rs748759187, rs368609628, rs1553345874, rs121918795, rs1266877537, rs1553266166, rs1553522321, rs1553543215, rs1553525325, rs1553520530, rs1553544470, rs1553551493, rs1553553462, rs1553560831, rs201966711, rs537026414, rs1559101839, rs1559114303, rs1559149128, rs1553553527, rs1569006250, rs781657502, rs1574370981, rs1366966423, rs1574312497, rs796053036, rs1573949198, rs1573953706, rs1573963975, rs1573973548, rs1573984110, rs1574005699, rs1574007140, rs1574052179, rs1574069132, rs1574166948, rs1574168611, rs1574183148, rs886041292, rs1574208760, rs1574209023, rs1574217232, rs1553545567, rs796053094, rs1574240716, rs1553549471, rs1574264920, rs1574266816, rs1574271602, rs1574271644, rs1574291210, rs1574371141, rs1574371902, rs796052488, rs1581220163, rs1196223064, rs1574182550, rs1573953030, rs1574201555, rs1574281711, rs1696401617, rs1692166604, rs1574006637, rs1689139851, rs1689186812, rs1689309551, rs1689680658, rs1697997770, rs1698732089, rs1698941202, rs1697667767, rs1691073965, rs1698009615	7626071
Sandhoff disease	Sandhoff Disease, Adult Sandhoff Disease, Infantile Sandhoff Disease, Juvenile Sandhoff Disease, Sandhoff Disease, Adult Type, Sandhoff Disease, Juvenile Type, Sandhoff Disease, Infantile Type, SANDHOFF DISEASE, CHRONIC, Sandhoff disease, infantile form, Sandhoff disease, adult form, Sandhoff disease, juvenile form	rs-1, rs28942073, rs121907983, rs121907985, rs5030731, rs1580377105, rs121907986, rs398123443, rs398123446, rs797044644, rs1114167287, rs761197472, rs886039499, rs573447174, rs776476415, rs753823903, rs762892362, rs373979283, rs1060499701, rs1453919511, rs764552042, rs201580118, rs1554034449, rs1554034452, rs1554036638, rs1554037170, rs1554034423, rs1554034447, rs1554034505, rs779328596, rs967720287, rs1554036523, rs768438206, rs1554036943, rs1554037076, rs1554037129, rs771973471, rs761117459, rs1554035308, rs1309123671, rs1554037120, rs1554037137, rs138914144, rs1007338250, rs1579950499, rs1579952143, rs1554034434, rs1748834145, rs1749049871, rs1749651392, rs775920504, rs1198764997, rs989299922, rs1554037088, rs1749130533	8950198, 23010210, 8162015, 7550345, 22789865, 9401004, 21150067, 1531140, 2522450, 27021291, 23127958, 24613245, 25736553, 24263030, 27604308, 23759947, 9475608, 7557963, 23113155, 9694901, 7626071, 8076944, 27682710, 18758829, 22848519, 1532910, 20798201, 12166653, 17015493, 2170400, 20926324, 23046579, 9856491, 9562328, 24356898, 21567908, 29448188, 1386607, 7633435, 19823769, 17237499, 2147031, 8357844, 25525159, 26582265, 1720305, 21483992
Macrocephaly	Macrocephaly	rs786204854, rs764333096, rs1557739557

Unknown
Disease name	Disease term	dbSNP ID	References
Dysarthria	Dysarthria
Erectile dysfunction	Erectile dysfunction
Hypohidrosis	Hypohidrosis
Kidney failure	Kidney Failure, Acute		22005293
Macroglossia	Macroglossia
Acute kidney insufficiency	Acute Kidney Insufficiency		22005293
Total hexosaminidase deficiency	Total Hexosaminidase Deficiency