GeneBe

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
PycnodysostosisARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingBiochemical; Craniofacial; Musculoskeletal14041831; 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 (291 variants)
  • Pyknodysostosis (159 variants)
  • Inborn_genetic_diseases (32 variants)
  • not_specified (7 variants)
  • Delayed_closure_of_the_anterior_fontanelle (1 variants)
  • Obtuse_angle_of_mandible (1 variants)
  • Abnormal_skull_morphology (1 variants)
  • Short_phalanx_of_finger (1 variants)
  • CTSK-related_disorder (1 variants)
  • Short_stature (1 variants)
  • Periodontitis (1 variants)
  • Scoliosis (1 variants)
  • Abnormal_cranial_suture/fontanelle_morphology (1 variants)
  • Skeletal_dysplasia (1 variants)
  • Enamel_hypoplasia (1 variants)
  • Short_finger (1 variants)
  • Increased_susceptibility_to_fractures (1 variants)
  • Midface_retrusion (1 variants)
  • Thoracic_scoliosis (1 variants)
  • Delayed_cranial_suture_closure (1 variants)
  • Nail_dysplasia (1 variants)
  • Macrocephaly (1 variants)
  • Abnormality_of_the_skeletal_system (1 variants)
  • Dental_crowding (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. These statistics are base on transcript: NM_000000396.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
105
clinvar
 113
missense
6
clinvar
25
clinvar
85
clinvar
5
clinvar
 121
nonsense
7
clinvar
19
clinvar
 26
start loss
1
2
 3
frameshift
22
clinvar
31
clinvar
 53
splice donor/acceptor (+/-2bp)
5
clinvar
14
clinvar
 19
Total 41 91 93 110 0

Highest pathogenic variant AF is 0.0000619574

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CTSKprotein_codingprotein_codingENST00000271651 712116
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.00003100.9431256960521257480.000207
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.9981341710.7850.000008882168
Missense in Polyphen5878.3190.74056934
Synonymous0.6635763.70.8940.00000321614
Loss of Function1.751018.00.5540.00000102211

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004960.000496
Ashkenazi Jewish0.000.00
East Asian0.0001090.000109
Finnish0.000.00
European (Non-Finnish)0.0002470.000246
Middle Eastern0.0001090.000109
South Asian0.00009800.0000980
Other0.0004890.000489

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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