CYLC2

Chr 9

cylicin 2

NCBI Gene: 1539ENSG00000155833UniProt: Q14093OMIM: 604035

Cylicin II is a testis-specific cytoskeletal protein that is required for acrosome attachment to the nuclear envelope and proper manchette elongation and disassembly during spermatogenesis, establishing normal sperm morphology. Mutations in CYLC2 cause autosomal dominant male infertility through a dominant-negative mechanism. The gene shows extreme intolerance to loss-of-function variants, consistent with its role in essential reproductive processes.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
DNmechanismLOEUF 1.46
Clinical Summary— CYLC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 67 VUS of 118 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.46LOEUF
pLI 0.000
Z-score 0.48
OE 0.84 (0.51–1.46)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.42Z-score
OE missense 1.31 (1.17–1.46)
223 obs / 170.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.84 (0.51–1.46)
0≤0.351.4
Missense OE1.31 (1.17–1.46)
0≤0.61.4
Synonymous OE1.20
0≤1.21.6
LoF obs/exp: 9 / 10.7Missense obs/exp: 223 / 170.9Syn Z: -1.21
DN
0.78top 25%
GOF
0.5268th %ile
LOF
0.4332th %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

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic2
VUS67
Likely Benign12
Benign1
Conflicting1
33
Pathogenic
2
Likely Pathogenic
67
VUS
12
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
2
0
2
VUS
0
61
6
0
67
Likely Benign
0
7
4
1
12
Benign
0
0
1
0
1
Conflicting
—1
Total068461116

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

View in ClinVar →

Protein Context — Lollipop Plot

CYLC2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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
Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human.
Schneider S et al.·Elife
2023
Mixed model-based eQTL analysis reveals lncRNAs associated with regulation of genes involved in sex determination and spermatogenesis: The key to understanding human gender imbalance.
An Y et al.·Comput Biol Chem
2022Functional
BCR::ZNF711 and BCR::CYLC2 Fusions: Novel BCR Fusions Expanding the Molecular Spectrum of Gene Fusions in Melanoma.
Ibrahim E et al.·Am J Dermatopathol
2024Case report
Identification of crucial genes related to postmenopausal osteoporosis using gene expression profiling.
Ma M et al.·Aging Clin Exp Res
2016
Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland.
Arnau-Soler A et al.·Transl Psychiatry
2019
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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