CTSD

Chr 11AR

cathepsin D

NCBI Gene: 1509ENSG00000117984UniProt: P07339

Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease

Primary Disease Associations & Inheritance

Ceroid lipofuscinosis, neuronal, 10MIM #610127
AR
558
ClinVar variants
60
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CTSD
🧬
Gene-Disease Validity (ClinGen)
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.
📋
ClinVar Variants
60 Pathogenic / Likely Pathogenic· 175 VUS of 558 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.001
Z-score 2.21
OE 0.44 (0.26–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.38Z-score
OE missense 0.76 (0.67–0.85)
190 obs / 251.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.44 (0.26–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.67–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 8 / 18.2Missense obs/exp: 190 / 251.6Syn Z: -0.91

ClinVar Variant Classifications

558 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic17
VUS175
Likely Benign266
Benign24
Conflicting33
43
Pathogenic
17
Likely Pathogenic
175
VUS
266
Likely Benign
24
Benign
33
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
2
28
0
43
Likely Pathogenic
13
1
3
0
17
VUS
2
122
49
2
175
Likely Benign
0
2
110
154
266
Benign
0
0
19
5
24
Conflicting
—33
Total28127209161558

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CTSD · protein map & ClinVar variants

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

Gene2Phenotype Curations

CTSD-related neuronal ceroid lipofuscinosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CATHEPSIN D; CTSD
MIM #116840 · *

Ceroid lipofuscinosis, neuronal, 10

MIM #610127

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CTSD
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy.
Wang K et al.·Autophagy
2023
Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.
Zhao D et al.·Circ Res
2024
Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.
Robak LA et al.·Brain
2017
AUF1-mediated inhibition of autophagic lysosomal degradation contributes to CagA stability and Helicobacter pylori-induced inflammation.
Zheng H et al.·Gut Microbes
2024
Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.
Matsuda J et al.·Autophagy
2020
GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions.
Brun S et al.·Autophagy
2022
A human-mouse atlas of intrarenal myeloid cells identifies conserved disease-associated macrophages in lupus nephritis.
Hoover PJ et al.·J Exp Med
2025Functional
Bioinformatic analysis constructs an optimal prognostic index for survival-related variables (OPISV) based on whole-genome expression data in Glioblastoma.
Pan J et al.·Int J Biol Macromol
2024
Atractylenolide I inhibits angiogenesis and reverses sunitinib resistance in clear cell renal cell carcinoma through ATP6V0D2-mediated autophagic degradation of EPAS1/HIF2α.
Li Q et al.·Autophagy
2025
LRRK2 is required for CD38-mediated NAADP-Ca(2+) signaling and the downstream activation of TFEB (transcription factor EB) in immune cells.
Nabar NR et al.·Autophagy
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Myeloid KIF13B suppresses the STT3A/CTSD/THBS1 Axis to prevent MASH.
Lu K et al.·Hepatology
2026
Snapin mediates neuronal PANoptosis after mild traumatic brain injury via H2S-dependent S-sulfhydration of CTSD.
Chen X et al.·J Adv Res
2026
SAMHD1 deficiency disrupts macrophage autophagy-lysosomal homeostasis and promotes inflammation via the mTOR-MITF-CTSD axis in ulcerative colitis.
Yaxian L et al.·Int J Biol Macromol
2025
Plastic additive bisphenol S induces depression by promoting AZU1/CTSD proteins to mediate plasma-related proteins and metabolites: A comprehensive multi-omics analysis.
Li NR et al.·Ecotoxicol Environ Saf
2025
Low-density lipoprotein receptor-related protein 6 ameliorates cardiac hypertrophy by regulating CTSD/HSP90α signaling during pressure overload.
Pan L et al.·Acta Pharmacol Sin
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Neuronal Ceroid LipofuscinosisBatten DiseaseCLN1 Disease

Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

RECRUITING
NCT04613089Universitätsklinikum Hamburg-EppendorfStarted 2020-04-08
Natural History

External Resources

Links to major genomics databases and tools