CALCOCO2
Chr 17calcium binding and coiled-coil domain 2
Also known as: NDP52
This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a receptor for ubiquitin-coated bacteria and plays an important role in innate immunity by mediating macroautophagy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]
Clinical Summary— CALCOCO2
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
11 Pathogenic / Likely Pathogenic· 52 VUS of 67 total submissions
Some data sources returned errors (1)
ensembl: TimeoutError: The operation was aborted due to timeout
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
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.
0.65LOEUF
pLI 0.000
Z-score 3.03
OE 0.40 (0.26–0.65)
Typical tolerance to LoF variation
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.
0.91Z-score
OE missense 0.83 (0.74–0.94)
197 obs / 236.5 exp
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.0.40 (0.26–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.74–0.94)
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.0.91
0≤1.21.6
LoF obs/exp: 12 / 29.9Missense obs/exp: 197 / 236.5Syn Z: 0.64
ClinVar Variant Classifications
67 submitted variants in ClinVar
Classification Summary
Pathogenic10
Likely Pathogenic1
VUS52
Likely Benign4
10
Pathogenic
1
Likely Pathogenic
52
VUS
4
Likely Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 10 | 0 | 10 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 47 | 5 | 0 | 52 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 51 | 16 | 0 | 67 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CALCOCO2 · 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
CALCIUM BINDING AND COILED-COIL DOMAIN PROTEIN 2; CALCOCO2
MIM #604587 · *
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD.
Larabi A et al.·Autophagy
2020Review
PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.
Araya J et al.·Autophagy
2019
Tethering ATG16L1 or LC3 induces targeted autophagic degradation of protein aggregates and mitochondria.
Mei L et al.·Autophagy
2023
Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy.
Leytens A et al.·Autophagy
2025
LRRK2 mutations impair depolarization-induced mitophagy through inhibition of mitochondrial accumulation of RAB10.
Wauters F et al.·Autophagy
2020
HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies.
Tedesco B et al.·Autophagy
2023
Targeted interplay between bacterial pathogens and host autophagy.
Sudhakar P et al.·Autophagy
2019Meta-analysis
A protective variant of the autophagy receptor CALCOCO2/NDP52 in Multiple Sclerosis (MS).
Di Rita A et al.·Autophagy
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
XIST Improves Mitophagy and Exerts Perioperative Myocardial Protection Through miR-212-3p/CALCOCO2/OPTN.
Zhou L et al.·APMIS
2026
Cuproptosis induced by curcumin interfering with proliferation and energy metabolism in colorectal cancer: 3D tumor model and computational simulations reveal curcumin inhibition of HSPD1 and CALCOCO2.
Cao JF et al.·Eur J Pharmacol
2025Functional
CALCOCO2 prevents AngII-induced atrial remodeling by regulating the interaction between mitophagy and mitochondrial stress.
Sang W et al.·Int Immunopharmacol
2024Functional
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Identification and validation of autophagy-related genes during osteogenic differentiation of bone marrow mesenchymal stem cells
Li Y et al.·Iran J Basic Med Sci
2022
Calcium-binding and coiled-coil domain 2 promotes the proliferation and suppresses apoptosis of prostate cancer cells.
Cui F et al.·Exp Ther Med
2021
A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk
Rottner AK et al.·Nat Genet
2023
Kaposi's sarcoma-associated herpesvirus (KSHV) utilizes the NDP52/CALCOCO2 selective autophagy receptor to disassemble processing bodies
Robinson CA et al.·PLoS Pathog
2023
Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
Chen L et al.·Open Med (Wars)
2024Cohort
Top 5 full-text resultsSearch PubTator3 ↗
External Resources
Links to major genomics databases and tools