NEK11

Chr 3

NIMA related kinase 11

NCBI Gene: 79858 ENSG00000114670 UniProt: Q8NG66 OMIM: 609779

This gene encodes a member of the never in mitosis gene A family of kinases. The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. The encoded protein appears to play roles in DNA replication and response to genotoxic stress. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.22

Clinical Summary— NEK11

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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

85 VUS of 122 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?

1.22LOEUF

pLI 0.000

Z-score 0.45

OE 0.92 (0.70–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.28Z-score

OE missense 1.04 (0.95–1.14)

353 obs / 338.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.92 (0.70–1.22)

0≤0.351.4

Missense OE?1.04 (0.95–1.14)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 34 / 37.0Missense obs/exp: 353 / 338.5Syn Z: 0.53

This gene — mechanism propensity

0.6745th %ile

GOF

0.7126th %ile

LOF

0.3551th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

122 submitted variants in ClinVar

ClinVar

Classification Summary

VUS85

Likely Benign11

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	84	0	85
Likely Benign	1	5	5	11
Benign	0	2	0	2
Total	2	91	5	98

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap NEK11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →