CCNL2

Chr 1

cyclin L2

Also known as: ANIA-6B, CCNM, CCNS, HCLA-ISO, HLA-ISO, PCEE, SB138

NCBI Gene: 81669ENSG00000221978UniProt: Q96S94

The protein is a regulatory component of the cyclin-L-CDK11 complex that controls transcription and pre-mRNA splicing, and may induce cell death by affecting transcription and RNA processing of apoptosis-related factors. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene shows autosomal recessive inheritance and is highly constrained against loss-of-function variants (LOEUF 0.47).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
135
P/LP submissions
0%
P/LP missense
0.47
LOEUF
DN
Mechanism· predicted
Clinical Summary— CCNL2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
128 unique Pathogenic / Likely Pathogenic· 116 VUS of 269 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.161
Z-score 3.68
OE 0.25 (0.14–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.54Z-score
OE missense 0.92 (0.84–1.01)
312 obs / 339.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.14–0.47)
0≤0.351.4
Missense OE0.92 (0.84–1.01)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 7 / 28.0Missense obs/exp: 312 / 339.9Syn Z: -1.20
DN
0.6550th %ile
GOF
0.5268th %ile
LOF
0.4825th %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

269 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic121
Likely Pathogenic7
VUS116
Likely Benign10
Benign1
121
Pathogenic
7
Likely Pathogenic
116
VUS
10
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
121
0
121
Likely Pathogenic
0
0
7
0
7
VUS
0
96
20
0
116
Likely Benign
0
3
3
4
10
Benign
0
0
1
0
1
Total0991524255

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

View in ClinVar →

Protein Context — Lollipop Plot

CCNL2 · 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 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 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