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FLASH GENE

Symbol

CST3

contributors: mct - updated : 21-12-2011

HGNC name	cystatin C (amyloid angiopathy and cerebral hemorrhage)
HGNC id	2475

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HCHWAI hereditary cerebral hemorrhage with amyloidosis
Location	20p11.21      Physical location : 23.614.293 - 23.618.574
Synonym name	neuroendocrine basic polypeptide
	cystatin C
Synonym symbol(s)	HCCAA, MGC117328, ARMD11, CYSc, CSTC

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	4.28 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

regionally located

clustered in a space of 900kb with other type 2 cystatin genes

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000099 3 - 818 - 146 - 2002 11879580

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 Digestive mouth           salivary gland submandibular       Lymphoid/Immune thymus       highly Nervous brain       highly reproductive epididymis       highly Reproductive female system ovary     highly   male system seminal vesicles         male system male genital tract vas deferens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial         Lymphoid

cell lineage
cell lines
fluid/secretion	highly in saliva, tears, seminal plasma, cerebrospinal fluid

at STAGE

PROTEIN

PHYSICAL PROPERTIES		basic		Hydrophobic
STRUCTURE

motifs/domains	two intramolecular disulfide bonds
	hydrophobic 26AA leader sequence

mono polymer

homomer , dimer

HOMOLOGY

interspecies

homolog to murine Cst3

Homologene

FAMILY

cystatin family

CATEGORY

enzyme , regulatory , secretory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum

basic FUNCTION	inhibitor of several cysteine proteinases, such as cathepsins S, B, and K
	inhibitor of cathepsin B, playing an important role of C in coronary artery disease
	inhibitor of CST6 in retinal pigment epithelium
	plays a role in cardiac extracellular matrix remodelling
	inhibitor for human meprin MEP1A
	CST3 an AHSG are endogenous inhibitors of human meprin metalloproteases
	regulates nitric oxide secretion by macrophages and is a TGFbeta antagonist
	may play an important role in the pathogenesis and metastasis of esophageal cancer

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	IRF8 is critical for CST3 expression in primary dendritic cells
	proteolytic target of cathepsin D (CTSD) and has a direct, causal impact on cell differentiation
	orchestrates cathepsin S expression through a tight but reversible interaction

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HCHWAI

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in Amyotrophic lateral sclerosis (ALS) patients were significantly elevated in plasma and reduced in cerebrospinal fluid (CSF)compared to healthy controls, but did not differ significantly from neurologic disease control

Susceptibility

to age related exudative macular degeneration late-onset Alzheimer disease (>75 years) to frontotemporal lobar degeneration (FTLD)

Variant & Polymorphism other	CST A allele risk factor for early-onset Alzheimers disease,B/B variant (ARMD)
	polymorphisms (-82G/C and -78T/G)significantly associated with coronary artery disease
	over-representation of the CST3 haplotype B and of AB/BB genotypes, in FTLD patients negative for the presence of GRN mutations

Candidate gene
Marker	correlations between CSF cystatin C levels to both ALS disease progression and patient survival
	S-cystatin C seems a useful marker for kidney function in the elderly
	maternal serum cystatin C concentrations in early pregnancy may be of value in identifying women at high risk of developing preeclampsia
	low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD
	may be an independent marker of atherosclerotic disease apart from its relation to kidney function
Therapy target

ANIMAL & CELL MODELS