CTSA

cathepsin A, the group of Cathepsins

Basic information

Region (hg38): 20:45890143-45898949

Previous symbols: [ "GSL", "PPGB" ]

Links

ENSG00000064601 ∙ NCBI:5476 ∙ OMIM:613111 ∙ HGNC:9251 ∙ Uniprot:P10619 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• galactosialidosis (Definitive), mode of inheritance: AR
• galactosialidosis (Definitive), mode of inheritance: AR
• galactosialidosis (Strong), mode of inheritance: AR
• galactosialidosis (Strong), mode of inheritance: AR
• galactosialidosis (Supportive), mode of inheritance: AR
• galactosialidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galactosialidosis	AR	Biochemical	Cardiac manifestations (eg, valvular anomalies and insufficiency) can be severe, and surveillance (eg, with echocardiogram) may allow early detection of sequalae and treatment; Cytopenias have been described; Renal transplanation has been described as beneficial	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	4999185; 3149149; 2148053; 8514852; 7759227; 8725271; 8968752; 9762607; 10944848; 18937050

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTSA gene.

• Combined deficiency of sialidase AND beta galactosidase (328 variants)
• not provided (54 variants)
• Inborn genetic diseases (31 variants)
• not specified (9 variants)
• Galactosialidosis, late infantile (3 variants)
• Galactosialidosis, early infantile (2 variants)
• Non-immune hydrops fetalis (1 variants)
• CTSA-related condition (1 variants)
• Abnormality of prenatal development or birth (1 variants)
• Galactosialidosis, adult (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTSA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	76	3	80
missense	2	2	117	2		123
nonsense	4	4	1			9
start loss			1			1
frameshift	18	2	2		1	23
inframe indel		1	5	3	1	10
splice donor/acceptor (+/-2bp)		6				6
splice region	1		19	11	1	32
non coding	1		17	53	18	89
Total	25	15	144	134	23

Highest pathogenic variant AF is 0.0000591

Variants in CTSA

This is a list of pathogenic ClinVar variants found in the CTSA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-45890493-G-A		not specified	Uncertain significance (Dec 20, 2023)
20-45890495-C-T		not specified	Uncertain significance (May 08, 2023)
20-45890516-A-G		not specified	Uncertain significance (Aug 15, 2023)
20-45890562-C-T		not specified	Uncertain significance (Oct 30, 2023)
20-45890565-C-T		not specified	Uncertain significance (Mar 14, 2023)
20-45890574-T-C		not specified	Likely benign (Sep 23, 2023)
20-45890585-C-CT			Likely benign (Oct 01, 2023)
20-45890622-G-A		not specified	Uncertain significance (Mar 21, 2023)
20-45890658-C-G		not specified	Uncertain significance (Sep 17, 2021)
20-45890723-G-A		not specified	Uncertain significance (Apr 25, 2022)
20-45890843-G-A		not specified	Uncertain significance (Dec 15, 2023)
20-45891004-G-A		Combined deficiency of sialidase AND beta galactosidase	Benign (Jun 28, 2018)
20-45891034-T-C		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Jun 14, 2016)
20-45891055-G-A		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Jun 14, 2016)
20-45891082-TC-T		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Jun 14, 2016)
20-45891088-CT-C		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Jun 14, 2016)
20-45891092-C-G		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Jun 14, 2016)
20-45891103-G-A		Combined deficiency of sialidase AND beta galactosidase	Likely benign (Jun 19, 2018)
20-45891154-A-C		Combined deficiency of sialidase AND beta galactosidase	Likely benign (Jun 14, 2016)
20-45891274-G-A		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Jun 14, 2016)
20-45891283-G-T		Combined deficiency of sialidase AND beta galactosidase	Benign/Likely benign (Jun 18, 2019)
20-45891331-T-C		Combined deficiency of sialidase AND beta galactosidase	Likely benign (Nov 06, 2022)
20-45891337-T-A		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Oct 27, 2021)
20-45891338-C-T		Combined deficiency of sialidase AND beta galactosidase	Uncertain significance (Jun 14, 2016)
20-45891339-C-T		Combined deficiency of sialidase AND beta galactosidase • Inborn genetic diseases	Uncertain significance (Jun 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTSA	protein_coding	protein_coding	ENST00000372484	15	8677

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.90e-9	0.963	121656	227	3865	125748	0.0164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.481	250	272	0.918	0.0000167	3235
Missense in Polyphen		52	72.558	0.71667		897
Synonymous	1.05	101	115	0.875	0.00000708	968
Loss of Function	2.08	18	30.4	0.593	0.00000145	340

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.124	0.116
Ashkenazi Jewish	0.00194	0.000993
East Asian	0.143	0.0655
Finnish	0.0223	0.0104
European (Non-Finnish)	0.00162	0.000879
Middle Eastern	0.143	0.0655
South Asian	0.0420	0.0206
Other	0.0280	0.0138

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins. {ECO:0000269|PubMed:1907282}.
• Disease: DISEASE: Galactosialidosis (GSL) [MIM:256540]: A lysosomal storage disease associated with a combined deficiency of beta- galactosidase and neuraminidase, secondary to a defect in cathepsin A. All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and a normal or mildly affected mental state. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. {ECO:0000269|PubMed:10944848, ECO:0000269|PubMed:1756715, ECO:0000269|PubMed:8514852, ECO:0000269|PubMed:8968752}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Renin-angiotensin system - Homo sapiens (human);Lysosome - Homo sapiens (human);Neutrophil degranulation;Metabolism of lipids;Post-translational protein modification;Metabolism of proteins;MHC class II antigen presentation;Innate Immune System;Immune System;Metabolism;Adaptive Immune System;De novo fatty acid biosynthesis;Sialic acid metabolism;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.782

Intolerance Scores

• loftool: 0.0690
• rvis_EVS: -0.87
• rvis_percentile_EVS: 10.73

Haploinsufficiency Scores

• pHI: 0.789
• hipred: Y
• hipred_score: 0.575
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.982

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ctsa
• Phenotype: immune system phenotype; renal/urinary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: proteolysis;glycosphingolipid metabolic process;intracellular protein transport;regulation of protein stability;positive regulation of catalytic activity;neutrophil degranulation;proteolysis involved in cellular protein catabolic process;regulation of chaperone-mediated autophagy;negative regulation of chaperone-mediated autophagy
• Cellular component: extracellular region;nucleoplasm;lysosome;endoplasmic reticulum;membrane;azurophil granule lumen;lysosomal lumen;intracellular membrane-bounded organelle;extracellular exosome;lumenal side of lysosomal membrane
• Molecular function: carboxypeptidase activity;serine-type carboxypeptidase activity;exo-alpha-sialidase activity;enzyme activator activity