CTSF

Chr 11AR

cathepsin F

Also known as: CATSF, CLN13

Cathepsin F is a lysosomal cysteine protease that degrades intracellular proteins as part of the lysosomal proteolytic system. Mutations cause neuronal ceroid lipofuscinosis type 13 (Kufs type), an adult-onset neurodegenerative disorder characterized by progressive cognitive decline and motor dysfunction, inherited in an autosomal recessive pattern. This gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting tolerance to complete protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.201 OMIM phenotype
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

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 OE0.84 (0.601.20)
00.351.4
Missense OE0.87 (0.780.97)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 22 / 26.2Missense obs/exp: 217 / 250.1Syn Z: -0.25
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.

3D Protein StructureAlphaFold
Clinical Literature
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