CRELD2

Chr 22

CRELD disulfide isomerase 2

NCBI Gene: 79174ENSG00000184164UniProt: Q6UXH1

Predicted to enable calcium ion binding activity and protein disulfide isomerase activity. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

275
ClinVar variants
138
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CRELD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
138 Pathogenic / Likely Pathogenic· 96 VUS of 275 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.
1.05LOEUF
pLI 0.000
Z-score 1.38
OE 0.68 (0.46–1.05)
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.
0.42Z-score
OE missense 0.92 (0.83–1.03)
221 obs / 239.2 exp
Tolerant

Mild missense constraint

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.0.68 (0.46–1.05)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.83–1.03)
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.1.02
0≤1.21.6
LoF obs/exp: 15 / 22.0Missense obs/exp: 221 / 239.2Syn Z: -0.13

ClinVar Variant Classifications

275 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic136
Likely Pathogenic2
VUS96
Likely Benign6
Benign4
136
Pathogenic
2
Likely Pathogenic
96
VUS
6
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
136
0
136
Likely Pathogenic
0
0
2
0
2
VUS
0
87
9
0
96
Likely Benign
0
3
0
3
6
Benign
1
0
1
2
4
Total1901485244

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

View in ClinVar →

Protein Context — Lollipop Plot

CRELD2 · 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
A preliminary study on the prognostic significance of cysteine-rich EGF ligand domain 2 protein (CRELD2) in patients with triple negative breast cancer.
Kocak MZ et al.·Biomol Biomed
2025Cohort
Targeting Endoplasmic Reticulum for Novel Therapeutics and Monitoring in Acute Kidney Injury.
Li C et al.·Nephron
2023Review
Development and Validation of AAV-Mediated Liver, Liver-VAT, and Liver-Brain SORT and Therapeutic Regulation of FASN in Hepatic De Novo Lipogenesis.
Bhadury R et al.·Cells
2025
Enhanced endoplasmic reticulum and mitochondrial stress in abdominal aortic aneurysm.
Navas-Madroñal M et al.·Clin Sci (Lond)
2019
A FBN1 3'UTR mutation variant is associated with endoplasmic reticulum stress in aortic aneurysm in Marfan syndrome.
Siegert AM et al.·Biochim Biophys Acta Mol Basis Dis
2019
Impact of novel oncogenic pathways regulated by antitumor miR-451a in renal cell carcinoma.
Yamada Y et al.·Cancer Sci
2018
A descriptive analysis of non-human leukocyte antigens present in renal transplant donor-recipient pairs.
Sisk LJ et al.·Transpl Immunol
2021
Case-inspired exploration of renin mutations in autosomal dominant tubulointerstitial kidney disease: not all paths lead to the endoplasmic reticulum.
Niedbalska-Tarnowska J et al.·Pediatr Nephrol
2024Case report
Identification of an endoplasmic reticulum stress-related gene signature to predict prognosis and potential drugs of uterine corpus endometrial cancer.
Zhou P et al.·Math Biosci Eng
2023
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