CTSD

Chr 11AR

cathepsin D

Also known as: CLN10, CPSD, HEL-S-130P

The protein is a lysosomal enzyme that breaks down proteins and activates hormones and growth factors through pepsin-like proteolytic activity. Mutations cause neuronal ceroid lipofuscinosis-10, an autosomal recessive lysosomal storage disorder. The pathogenic mechanism involves dominant-negative effects where mutant protein disrupts normal lysosomal function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.801 OMIM phenotype
Clinical SummaryCTSD
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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.
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ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 180 VUS of 500 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — CTSD
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.001
Z-score 2.21
OE 0.44 (0.260.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.38Z-score
OE missense 0.76 (0.670.85)
190 obs / 251.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.260.80)
00.351.4
Missense OE0.76 (0.670.85)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 8 / 18.2Missense obs/exp: 190 / 251.6Syn Z: -0.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCTSD-related neuronal ceroid lipofuscinosisLOFAR

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

DN
0.75top 25%
GOF
0.5856th %ile
LOF
0.2971th %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

500 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic12
VUS180
Likely Benign246
Benign13
Conflicting10
38
Pathogenic
12
Likely Pathogenic
180
VUS
246
Likely Benign
13
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
0
13
0
38
Likely Pathogenic
11
0
1
0
12
VUS
4
154
20
2
180
Likely Benign
1
2
116
127
246
Benign
0
0
13
0
13
Conflicting
10
Total41156163129499

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →