CTSK

Chr 1AR

cathepsin K

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

Cathepsin K is a lysosomal cysteine protease that degrades extracellular matrix and mediates osteoclastic bone resorption. Mutations cause pycnodysostosis, an autosomal recessive skeletal dysplasia characterized by osteosclerosis, short stature, and increased bone fragility. The gene shows very low constraint against loss-of-function variants (pLI 0.00003), which is consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.941 OMIM phenotype
Clinical SummaryCTSK
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Gene-Disease Validity (ClinGen)
pycnodysostosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.75
OE 0.55 (0.340.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.00Z-score
OE missense 0.79 (0.680.91)
134 obs / 170.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.55 (0.340.94)
00.351.4
Missense OE0.79 (0.680.91)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 10 / 18.0Missense obs/exp: 134 / 170.7Syn Z: 0.66
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCTSK-related pycnodysostosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.81top 10%
GOF
0.7127th %ile
LOF
0.2386th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
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