NEK3
protein-codingNIMA related kinase 3
Gene summary
This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein differs from other NimA family members in that it is not cell cycle regulated and is found primarily in the cytoplasm. The kinase is activated by prolactin stimulation, leading to phosphorylation of VAV2 guanine nucleotide exchange factor, paxillin, and activation of the RAC1 GTPase. Two functional alleles for this gene have been identified in humans. The reference genome assembly (GRCh38) represents a functional allele that is associated with the inclusion of an additional coding exon in protein-coding transcripts, compared to an alternate functional allele that lacks the exon. [provided by RefSeq, Sep 2019]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NEK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002498.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 73 | 4 | 1 | 78 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 79 | 5 | 1 | 85 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002489.1 | 15 | MANE Select | |
| Ensembl | ENSP00000480328.1 | 15 | MANE Select | |
| RefSeq | NP_001411183.1 | 14 | Standard | |
| RefSeq | NP_001411184.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prolactin Signaling Pathway
- JAK-STAT
- Prolactin
Biological Process
- mitotic cell cycle
- protein phosphorylation
- establishment of cell polarity
- neuron projection morphogenesis
- cell division
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- metal ion binding
Cellular Component
- nucleus
- cytoplasm
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400357
- Coding exons
- 14
- Length
- 27222
- Individuals with no LoFs
- 124466
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 188
- Defined
- 124654
- p
- 0.000754
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.197 | 242 | 251 | 0.965 | 0.0000126 | 3207 |
| Missense (PolyPhen) | 105 | 109.94 | 0.9551 | 1359 | ||
| Synonymous | 0.909 | 79 | 90.0 | 0.878 | 0.00000484 | 856 |
| Loss of Function | 0.136 | 27 | 27.8 | 0.972 | 0.00000152 | 348 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00061 | 0.00058 | rare |
| Latino/Admixed American | 0.00039 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0045 | 0.0045 | notable |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00064 | 0.00064 | rare |
| South Asian | 0.00029 | 0.00026 | rare |
| Other | 0.00067 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin- mediated phosphorylation of PXN and VAV2. Implicated in prolactin- mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2. {ECO:0000269|PubMed:15618286, ECO:0000269|PubMed:17297458}.;
Recessive Scores
- pRec
- 0.0888
Intolerance Scores
- RVIS EVS
- 0.2
- RVIS percentile EVS
- 67.3
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.832
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | High | High |