CCDC146

Chr 7

coiled-coil domain containing 146

Also known as: MBO2, SPGF94

NCBI Gene: 57639ENSG00000135205UniProt: Q8IYE0

Involved in spermatid development. Located in several cellular components, including microtubule organizing center; midbody; and sperm flagellum. Implicated in spermatogenic failure 94. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

UniProtSpermatogenic failure 94
174
ClinVar variants
18
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CCDC146
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 148 VUS of 174 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
1.07LOEUF
pLI 0.000
Z-score 1.11
OE 0.84 (0.66–1.07)
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.
0.88Z-score
OE missense 0.89 (0.82–0.96)
425 obs / 479.1 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.0.84 (0.66–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.82–0.96)
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.1.07
0≤1.21.6
LoF obs/exp: 45 / 53.8Missense obs/exp: 425 / 479.1Syn Z: -0.74

ClinVar Variant Classifications

174 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS148
Likely Benign8
17
Pathogenic
1
Likely Pathogenic
148
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
15
0
17
Likely Pathogenic
0
0
1
0
1
VUS
1
140
7
0
148
Likely Benign
0
5
2
1
8
Benign
0
0
0
0
0
Total2146251174

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

View in ClinVar →

Protein Context — Lollipop Plot

CCDC146 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lack of CCDC146, a ubiquitous centriole and microtubule-associated protein, leads to non-syndromic male infertility in human and mouse.
Muroňová J et al.·Elife
2024Functional
Early Progression Prediction in Korean Crohn's Disease Using a Korean-Specific PrediXcan Model.
Kim TW et al.·Int J Mol Sci
2025Functional
Discovery and characterization of tumor antigens in hepatocellular carcinoma for mRNA vaccine development.
Fu J et al.·J Cancer Res Clin Oncol
2023
The Human Centrosomal Protein CCDC146 Binds Chlamydia trachomatis Inclusion Membrane Protein CT288 and Is Recruited to the Periphery of the Chlamydia-Containing Vacuole.
Almeida F et al.·Front Cell Infect Microbiol
2018
Novel susceptibility loci identified in a genome-wide association study of type 2 diabetes complications in population of Latvia.
Ustinova M et al.·BMC Med Genomics
2021
Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes.
Wang K et al.·Prog Neuropsychopharmacol Biol Psychiatry
2021
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