CTSK

Chr 1

cathepsin K

Also known as: CTS02, CTSO, CTSO1, CTSO2, PKND, PYCD

NCBI Gene: 1513ENSG00000143387UniProt: P43235

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 also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature. [provided by RefSeq, Apr 2013]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPycnodysostosis

Clinical highlights

Gene-disease validity (ClinGen)
pycnodysostosis · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
260
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.94
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — CTSK
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.94LOEUF
pLI 0.000
Z-score 1.75
OE 0.55 (0.34–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.00Z-score
OE missense 0.79 (0.68–0.91)
134 obs / 170.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.55 (0.34–0.94)
0≤0.351.4
Missense OE?0.79 (0.68–0.91)
0≤0.61.4
Synonymous OE?0.89
0≤1.21.6
LoF obs/exp: 10 / 18.0Missense obs/exp: 134 / 170.7Syn Z: 0.66

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CTSK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients