CTSA

Chr 20ADAR

cathepsin A

Also known as: BSVD6, GLB2, GSL, NGBE, PPCA, PPGB

NCBI Gene: 5476 ENSG00000064601 UniProt: P10619 OMIM: 613111

The protein is a lysosomal serine carboxypeptidase with deamidase, esterase and carboxypeptidase activities that serves as a scaffold in the lysosomal multienzyme complex. Mutations cause galactosialidosis through autosomal recessive inheritance and brain small vessel disease 6 with leukoencephalopathy through autosomal dominant inheritance. The predicted mechanism of pathogenicity is dominant negative.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the peptidase S10 family of serine carboxypeptidases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate two chains that comprise the heterodimeric active enzyme. This enzyme possesses deamidase, esterase and carboxypeptidase activities and acts as a scaffold in the lysosomal multienzyme complex. Mutations in this gene are associated with galactosialidosis. [provided by RefSeq, Nov 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.882 OMIM phenotypes

Clinical Summary— CTSA

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Gene-Disease Validity (ClinGen)

galactosialidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

80 unique Pathogenic / Likely Pathogenic· 179 VUS of 624 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.08

OE 0.59 (0.41–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.48Z-score

OE missense 0.92 (0.83–1.02)

250 obs / 272.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.41–0.88)

0≤0.351.4

Missense OE?0.92 (0.83–1.02)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 18 / 30.4Missense obs/exp: 250 / 272.3Syn Z: 1.05

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCTSA-related galactosialidosisLOFAR

This gene — mechanism propensity

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

0.6840th %ile

GOF

0.6442th %ile

LOF

0.2581th %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

624 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40

Likely Pathogenic40

VUS179

Likely Benign306

Benign25

Conflicting20

Pathogenic

Likely Pathogenic

179

VUS

306

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	30	8	2	0	40
Likely Pathogenic	34	6	0	0	40
VUS	4	139	34	2	179
Likely Benign	0	5	157	144	306
Benign	1	1	20	3	25
Conflicting	—				20
Total	69	159	213	149	610

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap CTSA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →