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FLASH GENE

Symbol

SOSTDC1

contributors: mct/npt/pgu - updated : 09-09-2013

HGNC name	sclerostin domain containing 1
HGNC id	21748

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

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 heart       highly   vessel       moderately Digestive stomach       highly Urinary kidney tubule convoluted tubule distal tubule highly   kidney nephron renal capsule glomerulus highly Visual eye       highly

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Urinary epithelial cell Urinary podocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a CTCK (C-terminal cystine knot-like) domain

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to rattus Usag1
	ortholog to murine Sostdc1

intraspecies

paralog to SOST

Homologene

FAMILY

sclerostin family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	extracellular
text	secreted

basic FUNCTION	may be involved in the onset of endometrial receptivity for implantation/sensitization for the decidual cell reaction
	enhancing Wnt signaling
	inhibiting TGF-beta signaling
	directly antagonizing activity of BMP2, BMP4, BMP6 and BMP7 in a dose-dependent manner, in the developing and adult kidney
	negatively regulates the renoprotective action of BMP7
	with MEOX2, may have a role in the progression of Wilms tumorigenesis
	modulate Wnt signaling and also inhibit BMP signals, and modulation of Wnt signaling activity is brought about by an interaction with the Wnt co-receptor LRP6, whereas BMP inhibition is by binding to BMP ligands
	having multiple functions at the molecular level, suggesting a possible role in balancing Wnt and BMP signals
	plays crucial roles in tooth morphogenesis
	uncovers the role of dental mesenchyme in limiting tooth induction

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

enhancing Wnt signaling ; inhibiting TGF-beta signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	BMP2
	BMP4
	BMP6
	BMP7
	BMP antagonist
	binds LRP6 through one of three loops formed by the cystine knot
	HR repressed the expression of Wnt inhibitors, including SOSTDC1, DKKL1, SFRP1, and SFRP2
	interplay between LRP4 and SOSTDC1 in inhibiting Wnt/CTNNB1 signaling, providing an insight into how modulation of Wnt/CTNNB1 signaling controls cellular processes important for skin placode formation
	SOST and its paralog SOSTDC1 coordinate digit number in a GLI3-dependent manner
	VDR-mediated control of DKKL1, SOSTDC1, and HR gene expression in keratinocytes

cell & other

binds to neighboring cells and/or the extracellular matrix

REGULATION

induced by

by IHH is independent of GLI1

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       in Wilms tumor tumoral     --low   in renal clear cell carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer urinary   suppressing proliferation of renal carcinoma cells, restoration of SOSTDC1 signaling may represent a novel target in treatment of renal clear cell carcinoma

ANIMAL & CELL MODELS

Wise-null mice phenocopied a subset of the Lrp4 mammary defects and Wise overexpression reduced the number of mammary precursor cells