CTSF

Chr 11

cathepsin F

Also known as: CATSF, CLN13

Cathepsins are papain family cysteine proteinases that represent a major component of the lysosomal proteolytic system. Cathepsins generally contain a signal sequence, followed by a propeptide and then a catalytically active mature region. The very long (251 amino acid residues) proregion of the cathepsin F precursor contains a C-terminal domain similar to the pro-segment of cathepsin L-like enzymes, a 50-residue flexible linker peptide, and an N-terminal domain predicted to adopt a cystatin-like fold. The cathepsin F proregion is unique within the papain family cysteine proteases in that it contains this additional N-terminal segment predicted to share structural similarities with cysteine protease inhibitors of the cystatin superfamily. This cystatin-like domain contains some of the elements known to be important for inhibitory activity. CTSF encodes a predicted protein of 484 amino acids which contains a 19 residue signal peptide. Cathepsin F contains five potential N-glycosylation sites, and it may be targeted to the endosomal/lysosomal compartment via the mannose 6-phosphate receptor pathway. The cathepsin F gene is ubiquitously expressed, and it maps to chromosome 11q13, close to the gene encoding cathepsin W. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.20
Clinical SummaryCTSF
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Gene-Disease Validity (ClinGen)
adult neuronal ceroid lipofuscinosis · 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
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.20LOEUF
pLI 0.000
Z-score 0.75
OE 0.84 (0.601.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.74Z-score
OE missense 0.87 (0.780.97)
217 obs / 250.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.84 (0.601.20)
00.351.4
Missense OE?0.87 (0.780.97)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 22 / 26.2Missense obs/exp: 217 / 250.1Syn Z: -0.25

This gene — mechanism propensity

DN
0.6646th %ile
GOF
0.6442th %ile
LOF
0.3647th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CTSF · protein map & ClinVar variants

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