CCNL2

Chr 1

cyclin L2

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

NCBI Gene: 81669 ENSG00000221978 UniProt: Q96S94 OMIM: 613482

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).

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the cyclin family. Through its interaction with several proteins, such as RNA polymerase II, splicing factors, and cyclin-dependent kinases, this protein functions as a regulator of the pre-mRNA splicing process, as well as in inducing apoptosis by modulating the expression of apoptotic and antiapoptotic proteins. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

Mechanism· predicted

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 OE?0.25 (0.14–0.47)

0≤0.351.4

Missense OE?0.92 (0.84–1.01)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 7 / 28.0Missense obs/exp: 312 / 339.9Syn Z: -1.20

Background carrier burden — how many people carry a rare variant somewhere in CCNL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

763 rare PASS variants

Rare truncating (LoF)

1 in 3,300

76 rare PASS variants

Rare synonymous (reference)

1 in 140

360 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCNL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 3,000
South Asian	~43k	1 in 71	1 in 2,100
Remaining (unassigned)	~30k	1 in 72	1 in 6,000
European (Finnish)	~27k	1 in 210	1 in 1,600
Admixed American	~22k	1 in 79	≈ 1 in 4,500
African / African American	~21k	1 in 49	≈ 1 in 6,000
East Asian	~20k	1 in 67	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 420	none seen
Middle Eastern	~2,884	1 in 75	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓