CTSK

cathepsin K, the group of Cathepsins

Basic information

Region (hg38): 1:150794880-150809577

Previous symbols: [ "CTSO2", "CTSO", "PYCD" ]

Links

ENSG00000143387 ∙ NCBI:1513 ∙ OMIM:601105 ∙ HGNC:2536 ∙ Uniprot:P43235 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pycnodysostosis (Definitive), mode of inheritance: AR
• pycnodysostosis (Definitive), mode of inheritance: AR
• pycnodysostosis (Strong), mode of inheritance: AR
• pycnodysostosis (Strong), mode of inheritance: AR
• pycnodysostosis (Definitive), mode of inheritance: AR
• pycnodysostosis (Strong), mode of inheritance: AR
• pycnodysostosis (Supportive), mode of inheritance: AR
• pycnodysostosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pycnodysostosis	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Musculoskeletal	14041831; 14470123; 1611757; 8703060; 9529353; 10074491; 15070910; 17397052; 19674475; 20305575; 21099701

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTSK gene.

• not provided (25 variants)
• Pyknodysostosis (17 variants)
• 15 conditions (1 variants)
• 8 conditions (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTSK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	98	1	103
missense	5	17	47	4		73
nonsense	6	17				23
start loss	1	2				3
frameshift	18	27				45
inframe indel			5			5
splice donor/acceptor (+/-2bp)	5	13				18
splice region			5	20		25
non coding		1	9	43	15	68
Total	35	77	65	145	16

Highest pathogenic variant AF is 0.0000131

Variants in CTSK

This is a list of pathogenic ClinVar variants found in the CTSK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-150796332-T-C		Pyknodysostosis	Uncertain significance (Jan 13, 2018)
1-150796338-G-T		Pyknodysostosis	Uncertain significance (Jan 13, 2018)
1-150796457-G-A		Pyknodysostosis	Uncertain significance (Jan 12, 2018)
1-150796799-T-C		Pyknodysostosis	Pathogenic (Aug 30, 1996)
1-150796808-G-A			Likely benign (Jul 27, 2021)
1-150796813-A-C			Uncertain significance (Dec 14, 2021)
1-150796819-C-T		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
1-150796826-G-A			Likely benign (Jan 25, 2024)
1-150796829-A-T			Likely benign (Oct 24, 2022)
1-150796830-A-G		Inborn genetic diseases	Uncertain significance (Sep 04, 2024)
1-150796834-C-A			Uncertain significance (Jun 30, 2017)
1-150796836-C-T		Abnormality of the skeletal system • Pyknodysostosis	Pathogenic/Likely pathogenic (Mar 05, 2024)
1-150796838-G-A			Likely benign (Oct 23, 2022)
1-150796838-G-C			Likely benign (May 27, 2019)
1-150796840-CGT-C		Pyknodysostosis	Likely pathogenic (Jan 08, 2023)
1-150796841-G-A			Likely benign (Nov 16, 2023)
1-150796855-G-A		Pyknodysostosis	Pathogenic/Likely pathogenic (May 08, 2024)
1-150796855-G-C		Pyknodysostosis	Likely pathogenic (Jun 21, 2024)
1-150796855-G-T			Likely benign (Aug 30, 2022)
1-150796858-C-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 13, 2024)
1-150796862-G-A			Likely benign (Jan 16, 2024)
1-150796863-A-G		Pyknodysostosis	Pathogenic/Likely pathogenic (Oct 17, 2023)
1-150796864-G-A			Likely pathogenic (Oct 02, 2022)
1-150796868-A-G			Likely benign (Oct 23, 2023)
1-150796871-T-G			Likely benign (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTSK	protein_coding	protein_coding	ENST00000271651	7	12116

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000310	0.943	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.998	134	171	0.785	0.00000888	2168
Missense in Polyphen		58	78.319	0.74056		934
Synonymous	0.663	57	63.7	0.894	0.00000321	614
Loss of Function	1.75	10	18.0	0.554	0.00000102	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000496	0.000496
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Closely 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 degradation.
• Pathway: Lysosome - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Apoptosis - Homo sapiens (human);Osteoclast Signaling;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Type 2 papillary renal cell carcinoma;Gene expression (Transcription);Generic Transcription Pathway;Trafficking and processing of endosomal TLR;Toll-Like Receptors Cascades;Collagen degradation;RNA Polymerase II Transcription;Extracellular matrix organization;MHC class II antigen presentation;Innate Immune System;Immune System;Adaptive Immune System;Activation of Matrix Metalloproteinases;Degradation of the extracellular matrix;RUNX1 regulates transcription of genes involved in differentiation of keratinocytes;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.0995

Intolerance Scores

• loftool: 0.302
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.318
• hipred: N
• hipred_score: 0.282
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.222

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ctsk
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: autophagy of mitochondrion;intramembranous ossification;proteolysis;extracellular matrix disassembly;collagen catabolic process;bone resorption;regulation of keratinocyte differentiation;proteolysis involved in cellular protein catabolic process;negative regulation of cartilage development
• Cellular component: extracellular region;extracellular space;nucleoplasm;lysosome;endolysosome lumen;lysosomal lumen;intracellular membrane-bounded organelle
• Molecular function: fibronectin binding;cysteine-type endopeptidase activity;serine-type endopeptidase activity;protein binding;collagen binding;cysteine-type peptidase activity;proteoglycan binding