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FLASH GENE

Symbol

GBA

contributors: mct/npt/shn - updated : 23-10-2013

HGNC name	glucosidase, beta, acid
HGNC id	4177

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	GBA1 Gaucher disease, types I GBA2 Gaucher disease, types II GBA3 Gaucher disease, types III PARK24 Parkinson disease susceptibility, GBA related
Location	1q22      Physical location : 155.204.239 - 155.214.653
Synonym name	D-glucosyl-N-acylsphingosine glucohydrolase
	acid beta-glucosidase
	alglucerase; beta-glucocerebrosidase
	glucosylceramidase
	imiglucerase
	lysosomal glucocerebrosidase
Synonym symbol(s)	GLUC, GCB, GBA1
EC.number	3.2.1.45

DNA

TYPE	functioning gene
STRUCTURE	10.42 kb     12 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence
text structure	TATA boxes lie between nucleotides (-23)-(-27) and (-33)-(-39) and the two possible CAT boxes reside between nucleotides (-90)-(-94) and (-96)-(-99) in relation to the major 5' end of the mRNA

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D1S305 - D1S2714 - GBAP - D1S1153 - D1S2777 - qter
Authors	Cormand (97)
Text	[LDB ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001171811 10 - 2400 NP_001165282 - 449 - 2017 28126847 NM_000157 11 splicing 2324 NP_000148 59 536 - 2017 28126847 containing exon 3a (longer than 3b & 3c) lacking exons 1 & 2 NM_001005741 12 splicing 2432 NP_001005741 59 536 - 2017 28126847 containing exon 3b lacking exon 2 NM_001005742 12 splicing 2413 NP_001005742 59 536 - 2017 28126847 a 12 exons variant containing exon 3c (shorter than 3a & 3b) lacking exon 2 NM_001171812 10 splicing 2174 NP_001165283 - 487 - 2017 28126847

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel       highly Digestive esophagus       highly   liver       lowly   stomach       moderately Endocrine thyroid       moderately Lymphoid/Immune spleen       highly Nervous brain       highly Reproductive female system placenta     highly   female system breast mammary gland   moderately Respiratory respiratory tract trachea     moderately Skin/Tegument skin       highly Urinary bladder       moderately   kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     moderately Connective bone     moderately Nervous central     moderately

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Lymphoid/Immune macrophage

cell lineage
cell lines
fluid/secretion	blood

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to Gba, Mus musculus
	ortholog to Gba, Rattus norvegicus
	ortholog to gba, danio rerio

Homologene

FAMILY

glycosyl hydrolase 30 family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome
text	lysosomal membrane protein

basic FUNCTION	glucosidase
	glucocerebrosidase
	penultimate intermediate in the degradative pathway of complex glycolipids
	hydrolyzing glucosylceramide
	GBA and GBA2 are not only glucosylceramide beta-glucosidases but both also bile acid beta-glucosidases
	novel function of GBA1 as a Cholesteryl glucoside-synthesizing enzyme

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

lipid/lipoprotein

signaling

sphingolipid metabolism

a component

INTERACTION

DNA

RNA

small molecule

protein	parkin and mutant glucocerebrosidas
	TCP1 ring complex, TRiC and c-Cbl
	Alpha-synuclein
	Hsp70 and Hsp90
	GBA, GBA2, both have glucosylceramide as a main natural substrate
	ITCH interacts with mutant GBA variants and mediates their lysine 48 polyubiquitination and degradation
	SNCA interacts with GBA and efficiently inhibits enzyme activity
	PSAP a protein vital for GBA activity, protects GBA against SNCA inhibition
	lysosomal activity of GBA is tightly linked to expression of its trafficking receptor, SCARB2
	lipids regulate the hydrolysis of membrane bound glucosylceramide by GBA

cell & other

REGULATION

Other

targeted to the lysosome by M6P receptor mediated pathway

ASSOCIATED DISORDERS

corresponding disease(s)

GBA1 , GBA2 , GBA3 , PARK24

related resource

Gaucher Disease at GeneDis

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       GBA mutations may be associated with pathologically "purer" Lewy Body disorders, characterized by more extensive (cortical) LB, and less severe AD pathological findings and may be a useful marker for LB disorders constitutional       loss of function loss of GBA activity is sufficient to cause lysosomal dysfunction and accumulation of alpha-synuclein aggregates constitutional     --low   in sporadic Parkinson disease are related to the abnormal accumulation of SNCA and are associated with substantial alterations in lysosomal chaperone-mediated autophagy pathways and lipid metabolism

Susceptibility

to Parkinson disease

Variant & Polymorphism other	strong association between GBA mutations and Parkinson disease (Sidransky 2009)

Candidate gene	GBA mutations may be associated with pathologically "purer" Lewy body (LB) disorders, characterized by more extensive (cortical) LB, and less severe Alzheimer disease pathological findings and may be a useful marker for LB disorders (Clark 2009)
Marker
Therapy target	potent therapeutic potential of HDAC inhibitors as SAHA and LB-205 molecules for the treatment of Gaucher disease

ANIMAL & CELL MODELS

	a natural canine model of Gaucher disease mice homozygous for the RecNciI mutation had little GC enzyme activity and accumulated glucosylceramide in brain and liver, mice homozygous for the L444P mutation had higher levels of GC activity and no detectable accumulation of glucosylceramide in brain and liver, both point mutation mice died within 48 hr of birth
	mouse with strong reduction in GCase activity in all tissues except the skin exhibit rapid motor dysfunction associated with severe neurodegeneration and apoptotic cell death within the brain