CTSK (cathepsin K)

Gene

• Entrez ID: 1513
• Gene name: Cathepsin K
• Gene symbol: CTSK
• Synonyms: CTS02, CTSO, CTSO1, CTSO2, PKND, PYCD
• Chromosome: 1
• Chromosome location: 1q21.3
• Summary: The protein encoded by this gene is a lysosomal cysteine proteinase involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is predominantly expressed in osteoclasts. However, the encoded protein is

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs29001685	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs74315301	T>C	Pathogenic	Terminator codon variant, stop lost
rs74315302	C>G	Pathogenic	Missense variant, coding sequence variant
rs74315303	G>A,T	Likely-pathogenic	Stop gained, coding sequence variant, synonymous variant
rs74315304	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs74315305	C>T	Pathogenic	Missense variant, coding sequence variant
rs74315306	T>A	Pathogenic	Stop gained, coding sequence variant
rs75481239	A>C,T	Likely-pathogenic	Splice donor variant
rs142097792	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, synonymous variant
rs202040269	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs371277428	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs375958814	G>A,C,T	Likely-pathogenic	Synonymous variant, coding sequence variant, missense variant, stop gained
rs758450569	->TT	Likely-pathogenic	Frameshift variant, coding sequence variant
rs762780994	C>T	Pathogenic	Coding sequence variant, missense variant
rs773943327	AG>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs778368118	C>A,T	Likely-pathogenic	Initiator codon variant, missense variant
rs780202604	A>T	Likely-pathogenic	Coding sequence variant, stop gained
rs781168584	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs868112062	A>G	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs1057516514	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057516587	T>C	Likely-pathogenic	Splice acceptor variant
rs1057516627	TCCAGGGCACCCACAGAGCTAAAAGCCC>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057516725	T>-,TT	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057516790	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057516839	A>-	Likely-pathogenic	Splice donor variant
rs1057516891	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057517252	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057517263	C>T	Likely-pathogenic	Splice donor variant
rs1057517279	C>A,T	Likely-pathogenic	Splice donor variant
rs1553196764	->GCTGTAAGACCAATCAAGAAAAA	Likely-pathogenic	Intron variant, coding sequence variant, splice acceptor variant
rs1553196900	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1553196906	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1553196934	C>T	Likely-pathogenic	Splice donor variant
rs1553196945	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1553197230	C>T	Likely-pathogenic	Splice donor variant
rs1553197239	GG>C	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1553197262	C>G	Likely-pathogenic	Splice acceptor variant
rs1557823855	C>A	Pathogenic	Splice acceptor variant
rs1571122183	C>T	Uncertain-significance, pathogenic	Coding sequence variant, stop gained
rs1571123333	G>A	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT038461	hsa-miR-296-3p	CLASH	23622248
MIRT915948	hsa-miR-23a	CLIP-seq
MIRT915949	hsa-miR-23b	CLIP-seq
MIRT915950	hsa-miR-23c	CLIP-seq
MIRT915951	hsa-miR-3154	CLIP-seq
MIRT915952	hsa-miR-7	CLIP-seq
MIRT2510478	hsa-miR-127-5p	CLIP-seq
MIRT2510479	hsa-miR-128	CLIP-seq
MIRT2510480	hsa-miR-1293	CLIP-seq
MIRT2510481	hsa-miR-185	CLIP-seq
MIRT2510482	hsa-miR-197	CLIP-seq
MIRT2510483	hsa-miR-2110	CLIP-seq
MIRT2510484	hsa-miR-216a	CLIP-seq
MIRT2510485	hsa-miR-3153	CLIP-seq
MIRT2510486	hsa-miR-3613-3p	CLIP-seq
MIRT2510487	hsa-miR-3973	CLIP-seq
MIRT2510488	hsa-miR-3974	CLIP-seq
MIRT2510489	hsa-miR-3977	CLIP-seq
MIRT2510490	hsa-miR-4264	CLIP-seq
MIRT2510491	hsa-miR-4270	CLIP-seq
MIRT2510492	hsa-miR-4271	CLIP-seq
MIRT2510493	hsa-miR-4306	CLIP-seq
MIRT2510494	hsa-miR-4441	CLIP-seq
MIRT2510495	hsa-miR-4476	CLIP-seq
MIRT2510496	hsa-miR-4483	CLIP-seq
MIRT2510497	hsa-miR-4533	CLIP-seq
MIRT2510498	hsa-miR-4644	CLIP-seq
MIRT2510499	hsa-miR-4672	CLIP-seq
MIRT2510500	hsa-miR-4686	CLIP-seq
MIRT2510501	hsa-miR-4688	CLIP-seq
MIRT2510502	hsa-miR-4701-5p	CLIP-seq
MIRT2510503	hsa-miR-4724-5p	CLIP-seq
MIRT2510504	hsa-miR-4725-3p	CLIP-seq
MIRT2510505	hsa-miR-4738-3p	CLIP-seq
MIRT2510506	hsa-miR-4797-3p	CLIP-seq
MIRT2510507	hsa-miR-486-3p	CLIP-seq
MIRT2510508	hsa-miR-579	CLIP-seq
MIRT2510509	hsa-miR-588	CLIP-seq
MIRT2678792	hsa-miR-106a	CLIP-seq
MIRT2678793	hsa-miR-106b	CLIP-seq
MIRT2510478	hsa-miR-127-5p	CLIP-seq
MIRT2510479	hsa-miR-128	CLIP-seq
MIRT2510480	hsa-miR-1293	CLIP-seq
MIRT2678794	hsa-miR-17	CLIP-seq
MIRT2510481	hsa-miR-185	CLIP-seq
MIRT2510482	hsa-miR-197	CLIP-seq
MIRT2678795	hsa-miR-20a	CLIP-seq
MIRT2678796	hsa-miR-20b	CLIP-seq
MIRT2510483	hsa-miR-2110	CLIP-seq
MIRT2510484	hsa-miR-216a	CLIP-seq
MIRT2510485	hsa-miR-3153	CLIP-seq
MIRT2510486	hsa-miR-3613-3p	CLIP-seq
MIRT2510487	hsa-miR-3973	CLIP-seq
MIRT2510488	hsa-miR-3974	CLIP-seq
MIRT2510489	hsa-miR-3977	CLIP-seq
MIRT2510490	hsa-miR-4264	CLIP-seq
MIRT2510491	hsa-miR-4270	CLIP-seq
MIRT2510492	hsa-miR-4271	CLIP-seq
MIRT2678797	hsa-miR-4287	CLIP-seq
MIRT2510493	hsa-miR-4306	CLIP-seq
MIRT2510494	hsa-miR-4441	CLIP-seq
MIRT2510495	hsa-miR-4476	CLIP-seq
MIRT2510496	hsa-miR-4483	CLIP-seq
MIRT2510497	hsa-miR-4533	CLIP-seq
MIRT2510498	hsa-miR-4644	CLIP-seq
MIRT2510499	hsa-miR-4672	CLIP-seq
MIRT2678798	hsa-miR-4685-3p	CLIP-seq
MIRT2510500	hsa-miR-4686	CLIP-seq
MIRT2510501	hsa-miR-4688	CLIP-seq
MIRT2510502	hsa-miR-4701-5p	CLIP-seq
MIRT2510503	hsa-miR-4724-5p	CLIP-seq
MIRT2510504	hsa-miR-4725-3p	CLIP-seq
MIRT2510505	hsa-miR-4738-3p	CLIP-seq
MIRT2510506	hsa-miR-4797-3p	CLIP-seq
MIRT2510507	hsa-miR-486-3p	CLIP-seq
MIRT2678799	hsa-miR-519a	CLIP-seq
MIRT2678800	hsa-miR-519b-3p	CLIP-seq
MIRT2678801	hsa-miR-519c-3p	CLIP-seq
MIRT2678802	hsa-miR-519d	CLIP-seq
MIRT2678803	hsa-miR-520g	CLIP-seq
MIRT2678804	hsa-miR-520h	CLIP-seq
MIRT2510508	hsa-miR-579	CLIP-seq
MIRT2510509	hsa-miR-588	CLIP-seq
MIRT2678805	hsa-miR-93	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
MITF	Activation	21602817
SPI1	Unknown	15304486

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000422	Process	Autophagy of mitochondrion	HMP	24912190
GO:0001968	Function	Fibronectin binding	IPI	22952693
GO:0002224	Process	Toll-like receptor signaling pathway	TAS
GO:0004197	Function	Cysteine-type endopeptidase activity	IBA	21873635
GO:0004197	Function	Cysteine-type endopeptidase activity	IDA	22952693
GO:0005515	Function	Protein binding	IPI	12504904
GO:0005518	Function	Collagen binding	IDA	22952693
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	11082042, 22952693
GO:0005654	Component	Nucleoplasm	IDA
GO:0005764	Component	Lysosome	IBA	21873635
GO:0005764	Component	Lysosome	IDA	11082042, 22365146
GO:0006508	Process	Proteolysis	TAS	7818555
GO:0006590	Process	Thyroid hormone generation	IDA	11082042
GO:0006955	Process	Immune response	IBA	21873635
GO:0008234	Function	Cysteine-type peptidase activity	IDA	19834056
GO:0016324	Component	Apical plasma membrane	IEA
GO:0022617	Process	Extracellular matrix disassembly	TAS
GO:0030574	Process	Collagen catabolic process	IDA	19834056, 22952693
GO:0030574	Process	Collagen catabolic process	TAS
GO:0036021	Component	Endolysosome lumen	TAS
GO:0043202	Component	Lysosomal lumen	TAS
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0043394	Function	Proteoglycan binding	IPI	22952693
GO:0045616	Process	Regulation of keratinocyte differentiation	TAS
GO:0051603	Process	Proteolysis involved in cellular protein catabolic process	IBA	21873635
GO:0051603	Process	Proteolysis involved in cellular protein catabolic process	IDA	11082042, 22952693

Other IDs

• MIM: 601105
• HGNC: 2536
• e!Ensembl: ENSG00000143387

Protein

• UniProt ID: P43235
• Protein name: Cathepsin K (EC 3.4.22.38) (Cathepsin O) (Cathepsin O2) (Cathepsin X)
• Protein function: Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix deg
• PDB: 1ATK, 1AU0, 1AU2, 1AU3, 1AU4, 1AYU, 1AYV, 1AYW, 1BGO, 1BY8, 1MEM, 1NL6, 1NLJ, 1Q6K, 1SNK, 1TU6, 1U9V, 1U9W, 1U9X, 1VSN, 1YK7, 1YK8, 1YT7, 2ATO, 2AUX, 2AUZ, 2BDL, 2R6N, 3C9E, 3H7D, 3KW9, 3KWB, 3KWZ, 3KX1, 3O0U, 3O1G, 3OVZ, 4DMX, 4DMY, 4N79, 4N8W, 4X6H, 4X6I, 4X6J, 4YV8, 4YVA, 5J94, 5JA7, 5JH3, 5TDI, 5TUN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08246	Inhibitor_I29	26 → 86	Cathepsin propeptide inhibitor domain (I29)	Domain
  PF00112	Peptidase_C1	115 → 328	Papain family cysteine protease	Domain

• Sequence:

  MWGLKVLLLPVVSFALYPEEILDTHWELWKKTHRKQYNNKVDEISRRLIWEKNLKYISIH
  NLEASLGVHTYELAMNHLGDMTSEEVVQKMTGLKVPLSHSRSNDTLYIPEWEGRAPDSVD
  YRKKGYVTPVKNQGQCGSCWAFSSVGALEGQLKKKTGKLLNLSPQNLVDCVSENDGCGGG
  YMTNAFQYVQKNRGIDSEDAYPYVGQEESCMYNPTGKAAKCRGYREIPEGNEKALKRAVA
  RVGPVSVAIDASLTSFQFYSKGVYYDESCNSDNLNHAVLAVGYGIQKGNKHWIIKNSWGE
  NWGNKGYILMARNKNNACGIANLASFPKM

• Sequence length: 329

Pathways

KEGG:

Lysosome
Apoptosis
Osteoclast differentiation
Toll-like receptor signaling pathway
Rheumatoid arthritis

Reactome:

Collagen degradation
Degradation of the extracellular matrix
Activation of Matrix Metalloproteinases
Trafficking and processing of endosomal TLR
MHC class II antigen presentation
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Arthritis	Degenerative polyarthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470	30664745
Brachydactyly	Brachydactyly	rs121908949, rs28937580, rs121909082, rs104894122, rs863223289, rs863223290, rs104894121, rs1587657302, rs863223292, rs74315386, rs74315387, rs28936397, rs753691079, rs121909348, rs121917852, rs121917853, rs121917854, rs121917855, rs121917859, rs121917861, rs267606873, rs267606872, rs267606985, rs267606986, rs267606987, rs267606988, rs28933082, rs397514519, rs869025613, rs869025614, rs886039878, rs1553540620, rs1057518333, rs1948841937, rs1948868228, rs1948842030, rs1948842142
Glioblastoma	Glioblastoma, Glioblastoma Multiforme	rs121913500, rs886042842, rs1555138291, rs1558518449, rs1567176006, rs1558650888	25356585
Hydrocephalus	Hydrocephalus	rs387907320, rs369384363, rs387907321, rs372127610, rs770273135, rs797045095, rs797045707, rs769795916, rs781251438, rs922703465, rs376078512, rs1567043467, rs1587149916, rs1586841546
Osteochondrodysplasia	Osteochondrodysplasias	rs386833498, rs104893919, rs104893916, rs386833492, rs121908078, rs386833497, rs386833507, rs200963884, rs121908077, rs786204675, rs763198695, rs1554095433, rs766836061
Osteomyelitis	Osteomyelitis	rs11125529, rs10936599, rs7675998, rs398652, rs755017
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	19428782, 16715494
Scoliosis	Scoliosis, unspecified	rs1057518828, rs147296805, rs758163506, rs1555613564, rs1596852902, rs1596853067, rs1596853085
Skeletal dysplasia	Skeletal dysplasia	rs121912632, rs121912633, rs121912634, rs121912636, rs121912637, rs267607147, rs387906324, rs267607150, rs397514473, rs398123438, rs515726153, rs515726154, rs515726162, rs515726163, rs515726172, rs757011098

Unknown
Disease name	Disease term	dbSNP ID	References
Brachycephaly	Brachycephaly
Dwarfism	Dwarfism
Frontal bossing	Frontal bossing
Giant cell glioblastoma	Giant Cell Glioblastoma		25356585
Hypodontia	Hypodontia
Impaired cognition	Impaired cognition
Micrognathism	Micrognathism
Osteoarthrosis deformans	Osteoarthrosis Deformans		30664745
Osteosclerosis	Osteosclerosis
Proptosis	Exophthalmos
Pycnodysostosis	Pycnodysostosis		10074491, 27092432, 10878663, 21217630, 27604308, 9529353, 19674475, 23175007, 28328823, 15163881, 12874701, 8938428, 23786531, 21569238, 21099701, 10491211, 17206399, 8703060, 10634420, 22822386, 17397052, 24767306, 15070910, 10571690, 25731711, 11181082, 24269275
Spondylolisthesis	Spondylolisthesis
Spondylolysis	Spondylolysis