CNTLN

Chr 9

centlein

Also known as: C9orf101, C9orf39, bA340N12.1

NCBI Gene: 54875 ENSG00000044459 UniProt: Q9NXG0 OMIM: 611870

The CNTLN protein is required for centrosome cohesion and recruitment of CEP68 to centrosomes, functioning in centriole-centriole cohesion and protein localization. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay, typically presenting in infancy with severe intellectual disability and growth retardation. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with recessive inheritance where heterozygous carriers are unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein domain specific binding activity; protein kinase binding activity; and protein-macromolecule adaptor activity. Involved in centriole-centriole cohesion. Located in centriole; centrosome; and cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.000

Z-score 0.16

OE 0.98 (0.81–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.37Z-score

OE missense 1.26 (1.19–1.33)

844 obs / 671.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.98 (0.81–1.19)

0≤0.351.4

Missense OE?1.26 (1.19–1.33)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 75 / 76.6Missense obs/exp: 844 / 671.4Syn Z: -3.56

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 30

2,264 rare PASS variants

Rare truncating (LoF)

1 in 300

407 rare PASS variants

Rare synonymous (reference)

1 in 44

769 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNTLN. 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 37	1 in 330
South Asian	~43k	1 in 27	1 in 200
Remaining (unassigned)	~30k	1 in 24	1 in 250
European (Finnish)	~27k	1 in 81	1 in 400
Admixed American	~22k	1 in 25	1 in 150
African / African American	~21k	1 in 20	1 in 250
East Asian	~20k	1 in 28	1 in 210
Ashkenazi Jewish	~13k	1 in 210	1 in 540
Middle Eastern	~2,884	1 in 34	1 in 360

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 26 coding exons well covered in gnomAD exomes; exon 26 poorly covered; exons 3, 6, 13, 14, 19 and 3 more marginal. Genomes: all 26.? see exons ↓