CENPN

Chr 16

centromere protein N

Also known as: BM039, C16orf60, CENP-N, ICEN32

NCBI Gene: 55839 ENSG00000166451 UniProt: Q96H22 OMIM: 611509

The protein forms part of the nucleosome-associated complex that is essential for kinetochore assembly and chromosome segregation by directly binding to CENPA nucleosomes at centromeres. Mutations cause autosomal recessive primary microcephaly with growth retardation and developmental delays. This gene is moderately constrained against loss-of-function variants, and the condition typically presents in early infancy with severe microcephaly and failure to thrive.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene forms part of the nucleosome-associated complex and is important for kinetochore assembly. It is bound to kinetochores during S phase and G2 and recruits other proteins to the centromere. Pseudogenes of this gene are located on chromosome 2. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

OMIM ResearchGenerating clinical summary…

LOEUF 0.65

Clinical Summary— CENPN

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Population Constraint (gnomAD)

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

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ClinVar Variants

54 VUS of 86 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.004

Z-score 2.81

OE 0.36 (0.21–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.43Z-score

OE missense 1.09 (0.97–1.22)

202 obs / 185.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.65)

0≤0.351.4

Missense OE?1.09 (0.97–1.22)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 8 / 22.3Missense obs/exp: 202 / 185.7Syn Z: -1.36

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	54	54
Likely Benign	4	4
Benign	0	0
Total	58	58

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

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42 pathogenic / likely-pathogenic (of 75) ClinVar copy-number / structural variants overlap CENPN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →