Cystatin SN is a cysteine protease inhibitor found in saliva, tears, urine, and seminal fluid that inhibits enzymes including papain and dipeptidyl peptidase I. The gene shows very low constraint against loss-of-function variants (LOEUF 1.96), and no established disease associations with CST1 mutations have been reported in the literature. This gene encodes one of several related cystatin proteins that likely provide protective functions in human secretions.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
28
Pubs (1 yr)
20
P/LP submissions
0%
P/LP missense
1.96
LOEUF
DN
Mechanism· predicted
Clinical SummaryCST1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 39 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.96LOEUF
pLI 0.000
Z-score -1.79
OE 1.88 (1.001.96)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.20Z-score
OE missense 1.68 (1.461.91)
141 obs / 84.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.88 (1.001.96)
00.351.4
Missense OE1.68 (1.461.91)
00.61.4
Synonymous OE1.75
01.21.6
LoF obs/exp: 9 / 4.8Missense obs/exp: 141 / 84.1Syn Z: -3.52
DN
0.7327th %ile
GOF
0.4874th %ile
LOF
0.2484th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

69 submitted variants in ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic3
VUS39
Likely Benign8
17
Pathogenic
3
Likely Pathogenic
39
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
3
0
3
VUS
0
37
2
0
39
Likely Benign
0
5
1
2
8
Benign
0
0
0
0
0
Total04223267

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

View in ClinVar →

Protein Context — Lollipop Plot

CST1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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