CRISP2

Chr 6

cysteine rich secretory protein 2

Also known as: CRISP-2, CT36, GAPDL5, TPX1, TSP1

NCBI Gene: 7180ENSG00000124490UniProt: P16562

Predicted to be involved in sexual reproduction. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2025]

51
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CRISP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 39 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.
1.68LOEUF
pLI 0.000
Z-score -0.49
OE 1.14 (0.78–1.68)
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.
-0.46Z-score
OE missense 1.11 (0.97–1.28)
143 obs / 128.5 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.1.14 (0.78–1.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.97–1.28)
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.0.95
0≤1.21.6
LoF obs/exp: 17 / 15.0Missense obs/exp: 143 / 128.5Syn Z: 0.30

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS39
Likely Benign4
5
Pathogenic
3
Likely Pathogenic
39
VUS
4
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
1
32
6
0
39
Likely Benign
0
1
2
1
4
Benign
0
0
0
0
0
Total13316151

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

View in ClinVar →

Protein Context — Lollipop Plot

CRISP2 · 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
Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease.
Istas G et al.·Sci Rep
2017
MicroRNA-27a-mediated repression of cysteine-rich secretory protein 2 translation in asthenoteratozoospermic patients.
Zhou JH et al.·Asian J Androl
2017Cohort
The expression of cysteine-rich secretory protein 2 (CRISP2) and its specific regulator miR-27b in the spermatozoa of patients with asthenozoospermia.
Zhou JH et al.·Biol Reprod
2015Cohort
Exploring the dysregulated mRNAs-miRNAs-lncRNAs interactions associated to idiopathic non-obstructive azoospermia.
Sabetian S et al.·J Biomol Struct Dyn
2022
Fertilization defects in sperm from Cysteine-rich secretory protein 2 (Crisp2) knockout mice: implications for fertility disorders.
Brukman NG et al.·Mol Hum Reprod
2016
Hypodensity Beyond the Ischemic Core: Penumbral Changes Detected With Relative Noncontrast Computed Tomography.
Vandewalle L et al.·Stroke
2025
Single Cell Proteomics Profiling Reveals That Embryo-Secreted TNF-α Plays a Critical Role During Embryo Implantation to the Endometrium.
Lv J et al.·Reprod Sci
2022
[Expression of cysteine-rich secretory protein 2 in patients with asthenozoospermia and its clinical significance].
Zhou J et al.·Nan Fang Yi Ke Da Xue Xue Bao
2014Cohort
Pathogen-Related Yeast (PRY) proteins and members of the CAP superfamily are secreted sterol-binding proteins.
Choudhary V et al.·Proc Natl Acad Sci U S A
2012
Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis.
Salehi N et al.·Sci Rep
2021Functional
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