NLK
nemo like kinase
Basic information
Region (hg38): 17:28041737-28196381
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (30 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016231.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 30 | 30 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 30 | 0 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NLK | protein_coding | protein_coding | ENST00000407008 | 11 | 154645 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000887 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.56 | 117 | 287 | 0.408 | 0.0000151 | 3444 |
| Missense in Polyphen | 27 | 100.48 | 0.2687 | 1298 | ||
| Synonymous | 0.789 | 96 | 106 | 0.903 | 0.00000634 | 1021 |
| Loss of Function | 4.77 | 0 | 26.5 | 0.00 | 0.00000163 | 293 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Activation of this pathway causes binding to and phosphorylation of the histone methyltransferase SETDB1. The NLK- SETDB1 complex subsequently interacts with PPARG, leading to methylation of PPARG target promoters at histone H3K9 and transcriptional silencing. The resulting loss of PPARG target gene transcription inhibits adipogenesis and promotes osteoblastogenesis in mesenchymal stem cells (MSCs). Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). {ECO:0000250|UniProtKB:O54949, ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:17952062, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613}.;
- Pathway
- Adherens junction - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);WNT-Ncore;Mesodermal Commitment Pathway;Ectoderm Differentiation;Wnt Signaling Pathway;IL-6 signaling pathway;MAPK Signaling Pathway;Wnt Signaling Pathway and Pluripotency;Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;wnt signaling pathway;IL-7 signaling;Ca2+ pathway;Beta-catenin independent WNT signaling;JAK STAT pathway and regulation;Noncanonical Wnt signaling pathway;EPO signaling;C-MYB transcription factor network;IL6;Wnt;VEGF;Wnt Canonical;Wnt Mammals;Presenilin action in Notch and Wnt signaling
(Consensus)
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- loftool
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.09
Haploinsufficiency Scores
- pHI
- 0.967
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.656
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nlk
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; skeleton phenotype; immune system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- nlk2
- Affected structure
- optic tectum
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- MAPK cascade;regulation of transcription, DNA-templated;protein phosphorylation;transforming growth factor beta receptor signaling pathway;Wnt signaling pathway, calcium modulating pathway;regulation of gene expression;peptidyl-threonine phosphorylation;negative regulation of Wnt signaling pathway;intracellular signal transduction;serine phosphorylation of STAT protein;protein autophosphorylation;protein stabilization
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol
- Molecular function
- magnesium ion binding;protein kinase activity;protein serine/threonine kinase activity;MAP kinase activity;protein binding;ATP binding;transcription factor binding;ubiquitin protein ligase binding;SH2 domain binding