CEP112

Chr 17AR

centrosomal protein 112

Also known as: CCDC46, MACOCO, SPGF44

NCBI Gene: 201134ENSG00000154240UniProt: Q8N8E3

The protein recruits mRNAs essential for sperm development into phase-separated condensates to regulate their translation, and in neurons it localizes to dendrites and the nucleus where it interacts with Maf1 to regulate GABA-A receptor surface expression. Autosomal recessive mutations cause spermatogenic failure 44, resulting in male infertility. The pathogenic mechanism involves loss of function leading to disrupted mRNA regulation in reproductive tissues.

Summary from RefSeq, OMIM, UniProt, Mechanism

Primary Disease Associations & Inheritance

Spermatogenic failure 44MIM #619044
AR
0
Active trials
4
Pubs (1 yr)
15
P/LP submissions
7%
P/LP missense
1.13
LOEUF
DN
Mechanism· predicted
Clinical Summary— CEP112
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 126 VUS of 180 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 0.67
OE 0.91 (0.74–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.02Z-score
OE missense 1.00 (0.92–1.07)
478 obs / 479.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.91 (0.74–1.13)
0≤0.351.4
Missense OE1.00 (0.92–1.07)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 62 / 67.9Missense obs/exp: 478 / 479.4Syn Z: 0.15
DN
0.74top 25%
GOF
0.6052th %ile
LOF
0.3939th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

180 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic2
VUS126
Likely Benign10
Benign1
13
Pathogenic
2
Likely Pathogenic
126
VUS
10
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
12
0
13
Likely Pathogenic
0
0
2
0
2
VUS
0
94
32
0
126
Likely Benign
0
5
3
2
10
Benign
0
0
0
1
1
Total0100493152

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

View in ClinVar →

Protein Context — Lollipop Plot

CEP112 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients