CST7

Chr 20

cystatin F

Also known as: CMAP

CST7 encodes a glycosylated cysteine protease inhibitor that inhibits papain and cathepsin L and may regulate immune function through inhibition of targets in the hematopoietic system. Mutations cause autosomal recessive cerebellar ataxia with seizures and intellectual disability, with onset typically in early childhood. This gene is not highly constrained against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
19
Pubs (1 yr)
17
P/LP submissions
0%
P/LP missense
1.92
LOEUF
DN
Mechanism· predicted
Clinical SummaryCST7
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 21 VUS of 42 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.92LOEUF
pLI 0.000
Z-score -1.03
OE 1.45 (0.831.92)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.60Z-score
OE missense 1.18 (1.011.40)
100 obs / 84.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.45 (0.831.92)
00.351.4
Missense OE1.18 (1.011.40)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 9 / 6.2Missense obs/exp: 100 / 84.4Syn Z: -0.09
DN
0.7034th %ile
GOF
0.4875th %ile
LOF
0.3357th %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

42 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic3
VUS21
Likely Benign1
14
Pathogenic
3
Likely Pathogenic
21
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
3
0
3
VUS
0
17
4
0
21
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total01821039

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

View in ClinVar →

Protein Context — Lollipop Plot

CST7 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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