CST1

cystatin SN, the group of Cystatins, type 2

Basic information

Region (hg38): 20:23747562-23751268

Links

ENSG00000170373 ∙ NCBI:1469 ∙ OMIM:123855 ∙ HGNC:2473 ∙ Uniprot:P01037 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• male infertility with azoospermia or oligozoospermia due to single gene mutation (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CST1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CST1 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				2		2
missense			18	3		21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	5	0

Variants in CST1

This is a list of pathogenic ClinVar variants found in the CST1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-23747849-C-A		not specified	Uncertain significance (Jul 25, 2023)
20-23747850-C-A		not specified	Likely benign (Dec 03, 2021)
20-23747857-T-C		not specified	Likely benign (Dec 03, 2021)
20-23747872-C-T		not specified	Uncertain significance (Aug 13, 2021)
20-23749041-A-G		not specified	Uncertain significance (May 17, 2023)
20-23749072-T-C		not specified	Uncertain significance (Jul 09, 2021)
20-23749099-C-T		not specified	Uncertain significance (Sep 14, 2023)
20-23750650-C-T		not specified	Uncertain significance (Mar 20, 2024)
20-23750652-C-G		not specified	Uncertain significance (Mar 15, 2024)
20-23750662-G-A		not specified	Uncertain significance (May 25, 2022)
20-23750667-G-A		not specified	Uncertain significance (Oct 20, 2023)
20-23750668-G-C		not specified	Uncertain significance (Mar 29, 2022)
20-23750685-T-A		not specified	Uncertain significance (Jul 14, 2021)
20-23750707-C-T		not specified	Uncertain significance (Jan 23, 2023)
20-23750709-C-T		not specified	Uncertain significance (May 30, 2023)
20-23750752-G-T		not specified	Uncertain significance (Jul 21, 2021)
20-23750767-T-G		not specified	Uncertain significance (Sep 13, 2023)
20-23750769-C-A		not specified	Uncertain significance (May 18, 2022)
20-23750781-A-T		not specified	Uncertain significance (Feb 07, 2023)
20-23750815-C-T		not specified	Uncertain significance (Dec 28, 2022)
20-23750828-G-A			Likely benign (Jan 01, 2024)
20-23750840-C-T			Likely benign (Jan 01, 2024)
20-23750850-C-T		not specified	Uncertain significance (Jan 10, 2022)
20-23750856-T-G		not specified	Uncertain significance (Jul 05, 2023)
20-23750859-T-C		not specified	Likely benign (Nov 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CST1	protein_coding	protein_coding	ENST00000304749	3	3716

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.39e-8	0.0282	125715	0	30	125745	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.20	141	84.1	1.68	0.00000508	910
Missense in Polyphen		49	30.876	1.587		389
Synonymous	-3.52	63	36.1	1.75	0.00000233	273
Loss of Function	-1.79	9	4.78	1.88	2.02e-7	56

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000518	0.000517
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.000272	0.000272
South Asian	0.000131	0.000131
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Human saliva appears to contain several cysteine proteinase inhibitors that are immunologically related to cystatin S but that differ in their specificity due to amino acid sequence differences. Cystatin SN, with a pI of 7.5, is a much better inhibitor of papain and dipeptidyl peptidase I than is cystatin S, although both inhibit ficin equally well.
• Pathway: Salivary secretion - Homo sapiens (human);Vitamin D Receptor Pathway (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.870
• rvis_EVS: 0.42
• rvis_percentile_EVS: 76.96

Haploinsufficiency Scores

• pHI: 0.354
• 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: 0.0778

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;negative regulation of endopeptidase activity
• Cellular component: extracellular space
• Molecular function: cysteine-type endopeptidase inhibitor activity;protein binding