Gene: [05q13/HEXB] hexosaminidase B, beta polypeptide; gangliosidosis GM2, type II (Sandhoff disease); motor neuron disease, progressive;


To avoid confusion it should be noted that 'beta-N-' in enzyme name (-N- is often omitted) indicates the cleaving hexosamine structure, while 'beta-' without 'N' indicates an enzyme subunit. Sometimes the beta subunit is designated as B2 to notify that it is a part of an active enzyme as one of two covalently bound (via -S-S- bridge) peptides
(28 kD beta-A and 27 kD beta-B) produced by proteolysis of a 63 kD pre-beta-polypeptide."


[1] The gene length: 37 kb. Exons: 14 (556 aa), introns: 13 (Bikker-1989; Paw-1989). cDNA is 2.2 kb; ex1=100 amino acids, ex2=49, ex3=21, ex4=16, ex5=37, ex6=34, ex7=43, ex8=61, ex9=29, ex10=24, ex11=58, ex12=31, ex13=34, ex14=19. int1=3.9 kb, int2=4.1, int3=3.2, int4=0.2, int5=7.7, int6=8.2, int7=2.1, int8=0.8, int9=1.4, int10=0.5, int11=1.4, int12=0.3, int13=0.37 kb; int2 comprises two HindIII sites, one of which (3'-site) is polymorphic.
[2] The promoter region: Standard TATA box is absent but 3 GGGCGGG sites are found in positions -14, -80 and -126 upstream transcription initiation site (capping), as well as the complementary inverted CCGCCC site. A putative additional CAAT promoter (cacCAATtt) is in position -333. In general, promoter region structure is typical for housekeeping genes. There are two GC sites in open reading frame: GGGCGG in position +27, or 23 bp upstream to the first initiator codon (in position +50), and in position +81 (immediately anterior to the second initiator codon in position +87). The third initiator codon is in position +125.
[3] Poly(A)-signal gt is located at 87 bp downstream TTA stop codon, and poly(A)-site is 17 bp afterwards."


Systematic name: beta-N-acetyl-D-hexosaminide N-acetylhexosaminohydrolase. The enzyme catalyzes hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides."


The gene coding for alpha subunit, or hexosaminidase A (its deficiency causes Tay-Sachs gangliosidosis GM2/I) is located on chr 15q (GEM:15q2/HEXA)."


[1] The deficiency of both hexosaminidases is the pathogenetic basis of Sandhoff disease sometimes named as amaurotic idiocy. As a result ganglioside GM2 is accumulated in nervous system and internal organs.
[2] Psychomotoric retardation, hepatosplenomegaly, doll-like face, and macrocephaly are typical for Sandhoff disease. As the disease progresses, myoclonic seizures and spastic tetraparesis appear. Life span is 2 to 3 years."


The inheritance mode: autosomal recessive.


It is obvious from the subunit composition that beta subunit deficiency affects both main isoforms, A and B (in case of Sandhoff disease), whereas the isoform A only is deficient in Tay-Sachs disease (alpha subunit mutation, see GEM:15q2/HEXA). However, clinical cases have been described, in which beta peptide deficiency impairs the assembling of B but not A isoform (i.e. HEXB activity decreases while HEXA activity remains normal); see spinal amyotrophy description in Hancock-1985."


See GEM:15q2/HEXA.


Loci: GEM:00.0/SCZD1.
[1] HEXB ? SCZD1 (Kennedy-1988,1989; Sherrington-1989; Wood-1989)."


LOC "Balestrazzi P &: Hum Genet, 64, 305-308, 1983
MUT,GEN,PRO "Bikker H &: Hum Genet, 81, 287-288, 1989
MUT,FOG,PAT,PHE "Cashman &: Ann Neurol, 19, 568-572, 1986
LOC "Dana S &: Mol Cell Biol, 2, 1220-1228, 1982
LOC "Fox MF &: CCG, 38, 45-49, 1984
LOC "George DL, Francke: CCG, 22, (HGM4), 408-411, 1978
LOC "George DL, Francke: Somat Cell Genet, 3, 629-638, 1977
LOC "Gilbert F &: PNAS, 72, 263-267, 1975
LIN,MAG "Giuffra &: CCG, 51, (HGM10), 1004-1005, 1989
MUT,FOG,PAT,PHE "Hancock &: BBRC, 130, N3, 1185-1192, 1985
PRO,MUT,MOP "Hara Y &: Hum Genet, 94, 136-140, 1994
COM,LIN,PAT "Kennedy JL &: Schizophrenia Bull, 15, 0-0, 1989
COM,LIN,PAT "Kennedy JL &: Nature, 336, 167-170, 1988
PRO,SEQ,EXP,EVO "Korneluk RG &: JBC, 261, 8407-8413, 1986
MOP,STR,EVO,EXP "Mahuran DJ &: JBC, 263, N10, 4612-4618, 1988
MOP,STR,EVO,EXP "Mahuran DJ &: PNAS, 79, 1602-1605, 1982
MUT,GEN,PRO "Nakano T, Suzuki: JBC, 264, N9, 5155-5158, 1989
GEN,SEQ,STR,MOP "Neote K &: Genomics, 3, N4, 279-286, 1988
PRO,EXP,LOC,MOL "O'Dowd BF &: PNAS, 82, N4 (1 Feb), 1184-1188, 1985
MUT,GEN,PRO "Paw BH &: PNAS, 86, N7, 2413-2417, 1989
GEN,SEQ,STR,MOP "Proia RL: PNAS, 85, N6, 1883-1887, 1988
COM,LIN,PAT "Sherrington &: CCG, 51, (HGM10), 1077, 1989
PRO,MUT,MOP "Weiffenbach B &: Genomics, 10, 173-185, 1991
LIN,MAG "Weiffenbach B &: CCG, 51, (HGM10), 1104-1105, 1989
COM,LIN,PAT "Wood &: CCG, 51, (HGM10), 1110, 1989




lys, mtbd, carb, neu


coding, basic


05 q13


MIM: 268800