CCDC88B

Chr 11

coiled-coil domain containing 88B

NCBI Gene: 283234ENSG00000168071UniProt: A6NC98

Acts as a positive regulator of T-cell maturation and inflammatory function. Required for several functions of T-cells, in both the CD4(+) and the CD8(+) compartments and this includes expression of cell surface markers of activation, proliferation, and cytokine production in response to specific or non-specific stimulation (By similarity). Enhances NK cell cytotoxicity by positively regulating polarization of microtubule-organizing center (MTOC) to cytotoxic synapse, lytic granule transport along microtubules, and dynein-mediated clustering to MTOC (PubMed:25762780). Interacts with HSPA5 and stabilizes the interaction between HSPA5 and ERN1, leading to suppression of ERN1-induced JNK activation and endoplasmic reticulum stress-induced apoptosis (PubMed:21289099)

316
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CCDC88B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 275 VUS of 316 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.53LOEUF
pLI 0.000
Z-score 4.92
OE 0.39 (0.29–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.94Z-score
OE missense 0.91 (0.86–0.96)
777 obs / 854.6 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.0.39 (0.29–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.86–0.96)
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: 29 / 74.9Missense obs/exp: 777 / 854.6Syn Z: 1.38

ClinVar Variant Classifications

316 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS275
Likely Benign9
Benign1
6
Pathogenic
1
Likely Pathogenic
275
VUS
9
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
273
2
0
275
Likely Benign
0
8
0
1
9
Benign
0
0
0
1
1
Total028192292

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

View in ClinVar →

Protein Context — Lollipop Plot

CCDC88B · 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
Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci.
Goode EC et al.·Nat Commun
2024
Diagnostic yield and novel candidate genes by next generation sequencing in 166 children with intrahepatic cholestasis.
Zheng Y et al.·Hepatol Int
2024
GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels.
Casares-Marfil D et al.·PLoS Negl Trop Dis
2021
Identification of shared loci associated with both Crohn's disease and leprosy in East Asians.
Jung S et al.·Hum Mol Genet
2022Meta-analysis
Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.
Liu H et al.·Nat Genet
2015
Causal effects of brain subregion gene expression on inflammatory bowel diseases revealed by Mendelian randomization and single cell analysis.
Li Y et al.·Sci Rep
2025
Modifiable risk factors and inflammation-related proteins in polymyalgia rheumatica: genome-wide meta-analysis and Mendelian randomization.
Zhao SS et al.·Rheumatology (Oxford)
2025Meta-analysis
A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1.
Fischer A et al.·Am J Respir Crit Care Med
2012
Genomic structural equation modeling uncovers novel risk loci for bone metabolic disorders: cross-tissue genetic mechanisms and bone-brain axis regulation.
Zhou Y et al.·BMC Musculoskelet Disord
2025Functional
Yang-deficiency constitution drives poor outcomes in clear cell renal cell carcinoma by modulating the tumour immune microenvironment.
Kho BS et al.·Front Immunol
2025
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
Male Infertility

Efficacy Study of a Food Supplement With Myo-inositol, N-Acetyl-Cystein, Zinc and Vitamins on Sperm DNA Fragmentation

RECRUITING
NCT04959864Phase NAGYNOVStarted 2021-07-07
Isitol®Placebo

External Resources

Links to major genomics databases and tools