CRISP3

Chr 6

cysteine rich secretory protein 3

Also known as: Aeg2, CRISP-3, CRS3, SGP28, dJ442L6.3

NCBI Gene: 10321ENSG00000096006UniProt: P54108

This gene encodes a member of the cysteine-rich secretory protein (CRISP) family within the CRISP, antigen 5 and pathogenesis-related 1 proteins superfamily. The encoded protein has an N-terminal CRISP, antigen 5 and pathogenesis-related 1 proteins domain, a hinge region, and a C-terminal ion channel regulator domain. This protein contains cysteine residues, located in both the N- and C-terminal domains, that form eight disulfide bonds, a distinguishing characteristic of this family. This gene is expressed in the male reproductive tract where it plays a role in sperm function and fertilization, and the female reproductive tract where it plays a role in endometrial receptivity for embryo implantation. This gene is upregulated in certain types of prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

51
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CRISP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 40 VUS of 51 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.11LOEUF
pLI 0.000
Z-score 1.23
OE 0.67 (0.42–1.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.38Z-score
OE missense 1.09 (0.95–1.25)
150 obs / 137.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.67 (0.42–1.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (0.95–1.25)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 11 / 16.4Missense obs/exp: 150 / 137.5Syn Z: -0.98

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS40
Likely Benign3
5
Pathogenic
3
Likely Pathogenic
40
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
3
0
3
VUS
0
34
6
0
40
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total03714051

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

View in ClinVar →

Protein Context — Lollipop Plot

CRISP3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Upregulation of CRISP3 and its clinical values in adult sepsis: a comprehensive analysis based on microarrays and a two-retrospective-cohort study.
Zhang AQ et al.·Front Immunol
2024Meta-analysis
Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients' prognosis.
Al Bashir S et al.·J Hematol Oncol
2014Cohort
Multiple Myeloma: Genetic and Epigenetic Biomarkers with Clinical Potential.
Veryaskina YA et al.·Int J Mol Sci
2024
Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis.
Dahlman A et al.·Mod Pathol
2011
Variation in PTCHD2, CRISP3, NAP1L4, FSCB, and AP3B2 associated with spherical equivalent.
Chen F et al.·Mol Vis
2016
Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence.
Grupp K et al.·Mod Pathol
2013
Molecular mechanisms and treatment responses of pulmonary fibrosis in severe COVID-19.
Kooistra EJ et al.·Respir Res
2023Functional
Integrating bulk RNA-seq and scRNA-seq analyses with machine learning to predict platinum response and prognosis in ovarian cancer.
Gao T et al.·Sci Rep
2025
Unravelling of the comparative Transcriptomic Profile of Gallbladder Cancer using mRNA sequencing.
Dixit R et al.·Mol Biol Rep
2022
Immune Microenvironment and Response in Prostate Cancer Using Large Population Cohorts.
Ren X et al.·Front Immunol
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools