CST8

Chr 20

cystatin 8

Also known as: CRES, CTES5

NCBI Gene: 10047ENSG00000125815UniProt: O60676

The CST8 protein is a cysteine protease inhibitor that performs a specialized role during sperm development and maturation, with highly tissue-specific expression in the reproductive tract. This gene is not well-constrained against loss-of-function variants and currently has no established disease associations in pediatric neurology. Given its specific function in male reproductive biology, pathogenic variants would be expected to primarily affect fertility rather than neurological development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
21
P/LP submissions
0%
P/LP missense
1.65
LOEUF
DN
Mechanism· predicted
Clinical Summary— CST8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 30 VUS of 56 total submissions
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
1.65LOEUF
pLI 0.003
Z-score 0.49
OE 0.77 (0.38–1.65)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.26Z-score
OE missense 1.41 (1.20–1.66)
106 obs / 75.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.77 (0.38–1.65)
0≤0.351.4
Missense OE1.41 (1.20–1.66)
0≤0.61.4
Synonymous OE1.20
0≤1.21.6
LoF obs/exp: 4 / 5.2Missense obs/exp: 106 / 75.3Syn Z: -0.84
DN
0.77top 25%
GOF
0.4579th %ile
LOF
0.2386th %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

56 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic3
VUS30
Likely Benign3
18
Pathogenic
3
Likely Pathogenic
30
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
3
0
3
VUS
0
28
2
0
30
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total03024054

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

View in ClinVar →

Protein Context — Lollipop Plot

CST8 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients