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 SummaryCYLC2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.46LOEUF
pLI 0.000
Z-score 0.48
OE 0.84 (0.511.46)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.42Z-score
OE missense 1.31 (1.171.46)
223 obs / 170.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.84 (0.511.46)
00.351.4
Missense OE1.31 (1.171.46)
00.61.4
Synonymous OE1.20
01.21.6
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

0 submitted variants 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found