CST4

cystatin S, the group of Cystatins, type 2

Basic information

Region (hg38): 20:23685640-23689038

Links

ENSG00000101441 ∙ NCBI:1472 ∙ OMIM:123857 ∙ HGNC:2476 ∙ Uniprot:P01036 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CST4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CST4 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				3	2	5
missense			16	3	3	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	6	5

Variants in CST4

This is a list of pathogenic ClinVar variants found in the CST4 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-23685899-C-A			Benign (Feb 26, 2018)
20-23685967-C-A		not specified	Uncertain significance (Jan 18, 2025)
20-23685973-T-A		not specified	Uncertain significance (Jan 04, 2024)
20-23687095-A-G		not specified	Uncertain significance (May 31, 2023)
20-23687098-T-C		not specified	Uncertain significance (Dec 21, 2022)
20-23687099-C-T		not specified	Uncertain significance (May 21, 2024)
20-23687129-A-C		not specified	Uncertain significance (Sep 01, 2021)
20-23687142-C-T			Benign (Feb 26, 2018)
20-23687150-A-G		not specified	Uncertain significance (Feb 07, 2023)
20-23687158-C-T		not specified	Uncertain significance (Nov 21, 2022)
20-23687159-G-A		not specified	Uncertain significance (Jul 19, 2023)
20-23687170-A-T		not specified	Uncertain significance (Apr 22, 2022)
20-23687175-G-C		not specified	Likely benign (Dec 07, 2024)
20-23687194-C-G		not specified	Likely benign (Dec 20, 2023)
20-23687197-A-G		not specified	Uncertain significance (Jan 09, 2025)
20-23688795-T-C		not specified	Uncertain significance (Oct 06, 2022)
20-23688828-G-C		not specified	Uncertain significance (Mar 15, 2024)
20-23688851-T-C			Benign (Mar 30, 2018)
20-23688877-T-C			Likely benign (Dec 01, 2022)
20-23688890-T-C		not specified	Uncertain significance (Nov 18, 2022)
20-23688914-A-G		not specified	Uncertain significance (Oct 03, 2022)
20-23688916-A-G			Likely benign (Jun 01, 2023)
20-23688917-G-C		not specified	Uncertain significance (Jan 03, 2025)
20-23688920-C-T		not specified	Uncertain significance (Oct 20, 2024)
20-23688925-C-T			Likely benign (Dec 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CST4	protein_coding	protein_coding	ENST00000217423	3	3401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.68e-7	0.0829	125709	0	37	125746	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.07	138	84.5	1.63	0.00000512	913
Missense in Polyphen		37	22.93	1.6136		261
Synonymous	-2.63	53	33.6	1.58	0.00000203	269
Loss of Function	-1.01	8	5.46	1.46	3.16e-7	55

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.000761	0.000761
Finnish	0.00	0.00
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.000761	0.000761
South Asian	0.0000327	0.0000327
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This protein strongly inhibits papain and ficin, partially inhibits stem bromelain and bovine cathepsin C, but does not inhibit porcine cathepsin B or clostripain. Papain is inhibited non-competitively.
• Pathway: Salivary secretion - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.858
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.44

Haploinsufficiency Scores

• pHI: 0.0915
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.223

Gene Damage Prediction

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

Gene ontology

• Biological process: detection of chemical stimulus involved in sensory perception of bitter taste;retina homeostasis;negative regulation of endopeptidase activity;negative regulation of proteolysis
• Cellular component: extracellular space;extracellular exosome
• Molecular function: cysteine-type endopeptidase inhibitor activity