CETN1

Chr 18

centrin 1

Also known as: CEN1, CETN

NCBI Gene: 1068 ENSG00000177143 UniProt: Q12798 OMIM: 603187

The protein encoded by CETN1 localizes to the centrosome and plays a fundamental role in microtubule-organizing center structure and function, including determination of centrosome position and segregation during the cell cycle. Mutations in CETN1 cause autosomal recessive primary ciliary dyskinesia, a disorder affecting respiratory cilia function and sperm motility. The gene shows relatively low constraint to loss-of-function variation.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene plays important roles in the determination of centrosome position and segregation, and in the process of microtubule severing. This protein is localized to the centrosome of interphase cells, and redistributes to the region of the spindle poles during mitosis, reflecting the dynamic behavior of the centrosome during the cell cycle. [provided by RefSeq, Jan 2015]

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

1.48

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.48LOEUF

pLI 0.215

Z-score 1.06

OE 0.34 (0.12–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.82Z-score

OE missense 0.78 (0.66–0.94)

90 obs / 114.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.12–1.48)

0≤0.351.4

Missense OE?0.78 (0.66–0.94)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 1 / 3.0Missense obs/exp: 90 / 114.7Syn Z: 0.26

Background carrier burden — how many people carry a rare variant somewhere in CETN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 450

223 rare PASS variants

Rare truncating (LoF)

1 in 1,200

31 rare PASS variants

Rare synonymous (reference)

1 in 1,100

103 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CETN1; this gene does not show strong loss-of-function constraint by this measure. 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 600	1 in 1,100
South Asian	~43k	1 in 260	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 350	1 in 740
European (Finnish)	~27k	1 in 500	1 in 5,300
Admixed American	~22k	1 in 260	≈ 1 in 7,500
African / African American	~21k	1 in 290	1 in 3,600
East Asian	~20k	1 in 230	1 in 770
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 320	none seen

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓