NUAK2
gene geneOn this page
Also known as SNARKFLJ90349
Summary
NUAK2 (NUAK family kinase 2, HGNC:29558) is a protein-coding gene on chromosome 1q32.1, encoding NUAK family SNF1-like kinase 2 (Q9H093). Stress-activated kinase involved in tolerance to glucose starvation.
Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including cellular response to glucose starvation; protein phosphorylation; and regulation of hippo signaling. Located in nuclear speck. Implicated in anencephaly.
Source: NCBI Gene 81788 — RefSeq curated summary.
At a glance
- Gene–disease (curated): anencephaly 2 (Moderate, GenCC)
- GWAS associations: 10
- Clinical variants (ClinVar): 115 total — 1 pathogenic, 1 likely-pathogenic
- Phenotypes (HPO): 9
- Druggable target: yes — 34 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_030952
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:29558 |
| Approved symbol | NUAK2 |
| Name | NUAK family kinase 2 |
| Location | 1q32.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | SNARK, FLJ90349 |
| Ensembl gene | ENSG00000163545 |
| Ensembl biotype | protein_coding |
| OMIM | 608131 |
| Entrez | 81788 |
Gene structure
Transcript identifiers
Ensembl transcripts: 1 — 1 protein_coding
ENST00000367157
RefSeq mRNA: 1 — MANE Select: NM_030952
NM_030952
CCDS: CCDS1453
Canonical transcript exons
ENST00000367157 — 7 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001075851 | 205311705 | 205311825 |
| ENSE00001075853 | 205308165 | 205308230 |
| ENSE00001075855 | 205305199 | 205305331 |
| ENSE00001075858 | 205308581 | 205308732 |
| ENSE00001075861 | 205306188 | 205306307 |
| ENSE00001443657 | 205321398 | 205321745 |
| ENSE00001607276 | 205302063 | 205304513 |
Expression profiles
Bgee: expression breadth ubiquitous, 220 present calls, max score 95.26.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1400 / max 452.8664, expressed in 1521 samples.
FANTOM5 promoters (2 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 16970 | 18.0189 | 1519 |
| 16968 | 0.1210 | 59 |
Top tissues by expression
274 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| cervix squamous epithelium | UBERON:0006922 | 95.26 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 94.78 | gold quality |
| blood | UBERON:0000178 | 92.37 | gold quality |
| ileal mucosa | UBERON:0000331 | 92.09 | gold quality |
| oviduct epithelium | UBERON:0004804 | 91.72 | gold quality |
| tongue squamous epithelium | UBERON:0006919 | 91.43 | gold quality |
| metanephros cortex | UBERON:0010533 | 91.26 | gold quality |
| gingival epithelium | UBERON:0001949 | 90.81 | gold quality |
| cervix epithelium | UBERON:0004801 | 90.33 | gold quality |
| gingiva | UBERON:0001828 | 90.19 | gold quality |
| squamous epithelium | UBERON:0006914 | 89.87 | gold quality |
| esophagus mucosa | UBERON:0002469 | 89.60 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 89.00 | gold quality |
| granulocyte | CL:0000094 | 88.80 | gold quality |
| epithelium of esophagus | UBERON:0001976 | 87.89 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 87.65 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 87.53 | gold quality |
| renal medulla | UBERON:0000362 | 86.43 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 86.11 | gold quality |
| nephron tubule | UBERON:0001231 | 86.00 | gold quality |
| kidney epithelium | UBERON:0004819 | 85.83 | gold quality |
| metanephric glomerulus | UBERON:0004736 | 85.61 | gold quality |
| jejunal mucosa | UBERON:0000399 | 85.25 | gold quality |
| upper leg skin | UBERON:0004262 | 84.68 | gold quality |
| renal glomerulus | UBERON:0000074 | 84.67 | gold quality |
| oral cavity | UBERON:0000167 | 84.17 | gold quality |
| vagina | UBERON:0000996 | 83.98 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 83.74 | gold quality |
| cortex of kidney | UBERON:0001225 | 83.73 | gold quality |
| buccal mucosa cell | CL:0002336 | 83.55 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 6.02 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
100 targeting NUAK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-6867-5P | 100.00 | 82.21 | 3464 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-574-5P | 100.00 | 66.01 | 989 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-6870-5P | 99.99 | 68.55 | 2115 |
| HSA-MIR-548AW | 99.99 | 72.57 | 3559 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-4803 | 99.98 | 71.99 | 3117 |
| HSA-MIR-4723-5P | 99.97 | 68.70 | 2034 |
| HSA-MIR-5698 | 99.97 | 68.49 | 2029 |
| HSA-MIR-7111-5P | 99.97 | 68.48 | 2062 |
| HSA-MIR-23A-3P | 99.95 | 74.24 | 3163 |
| HSA-MIR-23B-3P | 99.95 | 74.24 | 3163 |
| HSA-MIR-23C | 99.95 | 73.92 | 3192 |
| HSA-MIR-497-5P | 99.92 | 71.83 | 2674 |
| HSA-MIR-15A-5P | 99.90 | 72.80 | 2787 |
| HSA-MIR-15B-5P | 99.90 | 72.78 | 2798 |
| HSA-MIR-16-5P | 99.90 | 72.80 | 2780 |
| HSA-MIR-195-5P | 99.90 | 72.81 | 2805 |
| HSA-MIR-4493 | 99.90 | 66.48 | 977 |
| HSA-MIR-4753-3P | 99.90 | 71.03 | 3786 |
| HSA-MIR-6838-5P | 99.89 | 71.94 | 2690 |
| HSA-MIR-424-5P | 99.89 | 71.90 | 2641 |
| HSA-MIR-7162-3P | 99.89 | 68.16 | 1682 |
| HSA-MIR-124-3P | 99.89 | 73.74 | 3043 |
| HSA-MIR-506-3P | 99.89 | 73.55 | 3057 |
| HSA-MIR-6780A-5P | 99.88 | 66.69 | 2776 |
Literature-anchored findings (GeneRIF, showing 23)
- This study describes the cloning and characterization of the rat SNARK homolog, mapping of the human SNARK gene to 1q32, and a potential functional role as mediator of the cellular response to metabolic stress. (PMID:11284715)
- SNARK is an NF-kappaB-regulated anti-apoptotic gene that contributes to the tumor-promoting activity of CD95 in apoptosis-resistant tumor cells (PMID:15345718)
- These data suggests different phosphorylation and regulation of MYPT1 activity by NUAK2. (PMID:18023418)
- EBV LMP1 upregulated the expression of SNARK; SNARK expression increased drug resistance in response to doxorubicin increased of cancer cell survival (PMID:18452098)
- The nuclear localizing SNARK altered transcriptome profiles and a considerable part of these alterations were canceled by the mutation of NLS, suggesting the ability of SNARK to modulate gene expression dependent on its nuclear localization. (PMID:18992219)
- Skeletal muscle SNARK expression is increased in human obesity, and in response to metabolic stressors, but not type 2 diabetes. Partial SNARK depletion failed to modify either glucose or lipid metabolism. (PMID:19652946)
- Data show that SNARK is activated by muscle contraction and is a unique mediator of contraction-stimulated glucose transport in skeletal muscle. (PMID:20713714)
- MLCP (myosin light chain phosphatase) activation is counteracted by a previously unrecognized association between MRIP (myosin phosphatase Rho-interacting protein) and the inducible kinase NUAK2 (PMID:21242312)
- This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties. (PMID:21460252)
- Considers possible roles of NUAK2 in tumorigenesis in general and suggest that NUAK2 has pivotal roles in acral melanomagenesis. (PMID:21911917)
- Activation of AMP-activated protein kinase protects the integrity of the blood-brain barrier by suppressing the induction of NADPH oxidase-derived superoxide anions. (PMID:22796592)
- The AMPK-related kinase SNARK regulates hepatitis C virus replication and pathogenesis through enhancement of TGF-beta signaling. (PMID:23831117)
- Sucrose non-fermenting AMPK related kinase/Pentraxin 3 combined role in immunometabolic signaling and DNA damage response is proposed to accelerate cardiovascular complications in systemic lupus erythematosus patients (PMID:25732129)
- NUAK2 silencing and inactivation of the PI3K pathway efficiently controlled CDK2 expression, whereas CDK2 inactivation specifically abrogated the growth of NUAK2-amplified and PTEN-deficient melanoma cells. (PMID:25832654)
- miR143 inhibited the proliferation, migration and invasion of the glioblastoma cells by degrading NUAK2 in glioblastoma. (PMID:27081712)
- Data (including data from studies in knockout and transgenic mice) suggest that NUAK2/SNARK is involved in both adipose inflammation and energy metabolism in adipocytes; additionally, genome-wide association studies suggest that 2 SNPs in NUAK2/SNARK (rs4682880, rs4682676) are associated with obesity in women. (PMID:29298809)
- NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP. (PMID:32001115)
- A loss-of-function NUAK2 mutation in humans causes anencephaly due to impaired Hippo-YAP signaling. (PMID:32845958)
- NUAK2 silencing inhibits the proliferation, migration and epithelialtomesenchymal transition of cervical cancer cells via upregulating CYFIP2. (PMID:34558636)
- GPR65 promotes intestinal mucosal Th1 and Th17 cell differentiation and gut inflammation through downregulating NUAK2. (PMID:35343079)
- Circ_0000033 up-regulates NUAK2 by sequestering miR-378a-3p to promote breast tumorigenesis. (PMID:37357410)
- Enhanced SARS-CoV-2 entry via UPR-dependent AMPK-related kinase NUAK2. (PMID:37421942)
- OTUD7B deubiquitinates and stabilizes YAP1 to upregulate NUAK2 expression, thus accelerating gastric cancer procession. (PMID:37429790)
Cross-species orthologs
9 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | nuak2 | ENSDARG00000063661 |
| mus_musculus | Nuak2 | ENSMUSG00000009772 |
| rattus_norvegicus | Nuak2 | ENSRNOG00000000034 |
| drosophila_melanogaster | Snrk | FBGN0033915 |
| drosophila_melanogaster | Nuak | FBGN0262617 |
| caenorhabditis_elegans | WBGENE00012638 | |
| caenorhabditis_elegans | ZK524.4 | WBGENE00013994 |
| caenorhabditis_elegans | tag-344 | WBGENE00015230 |
| caenorhabditis_elegans | WBGENE00044388 |
Paralogs (17): NUAK1 (ENSG00000074590), PRKAA1 (ENSG00000132356), TSSK4 (ENSG00000139908), HUNK (ENSG00000142149), SIK1 (ENSG00000142178), BRSK1 (ENSG00000160469), SIK3 (ENSG00000160584), PRKAA2 (ENSG00000162409), TSSK3 (ENSG00000162526), SNRK (ENSG00000163788), MELK (ENSG00000165304), SIK2 (ENSG00000170145), BRSK2 (ENSG00000174672), NIM1K (ENSG00000177453), TSSK6 (ENSG00000178093), TSSK2 (ENSG00000206203), TSSK1B (ENSG00000212122)
Protein
Protein identifiers
NUAK family SNF1-like kinase 2 — Q9H093 (reviewed: Q9H093)
Alternative names: Omphalocele kinase 2, SNF1/AMP kinase-related kinase
All UniProt accessions (1): Q9H093
UniProt curated annotations — full annotation on UniProt →
Function. Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway.
Post-translational modifications. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Autophosphorylation is also possible at Thr-208.
Disease relevance. Anencephaly 2 (ANPH2) [MIM:619452] A form of anencephaly, an extreme neural tube defect resulting in the absence of brain tissues, and death in utero or perinatally. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed. ANPH2 features may also include frontonasal dysplasia with midline cleft of the upper lip and alveolar ridge, bifid nose, and clinical anophthalmia. ANPH2 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.
Activity regulation. Activated by phosphorylation on Thr-208.
Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
RefSeq proteins (1): NP_112214* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000719 | Prot_kinase_dom | Domain |
| IPR008271 | Ser/Thr_kinase_AS | Active_site |
| IPR011009 | Kinase-like_dom_sf | Homologous_superfamily |
| IPR017441 | Protein_kinase_ATP_BS | Binding_site |
Pfam: PF00069
Catalyzed reactions (Rhea), 2 shown:
- L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
- L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)
UniProt features (23 total): modified residue 7, sequence variant 6, region of interest 2, mutagenesis site 2, binding site 2, chain 1, domain 1, compositionally biased region 1, active site 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9H093-F1 | 63.45 | 0.36 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1): 175 (proton acceptor)
Ligand- & substrate-binding residues (2): 59–67; 81
Post-translational modifications (7): 435, 523, 544, 547, 573, 1, 208
Mutagenesis-validated functional residues (2):
| Position | Phenotype |
|---|---|
| 81 | loss of autophosphorylation, kinase activity and of anti-apoptotic activity. |
| 208 | prevents phosphorylation and activation by stk11/lkb1 complex. |
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 154 (showing top):
GSE45365_NK_CELL_VS_CD11B_DC_DN, LEE_NEURAL_CREST_STEM_CELL_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_HIPPO_SIGNALING, RICKMAN_METASTASIS_DN, WTGAAAT_UNKNOWN, AACTTT_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_STARVATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, TAATGTG_MIR323, GOBP_CELLULAR_RESPONSE_TO_GLUCOSE_STARVATION, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, GOBP_RESPONSE_TO_STARVATION, TGGAAA_NFAT_Q4_01, GOMF_MAGNESIUM_ION_BINDING
GO Biological Process (7): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), actin cytoskeleton organization (GO:0030036), protein localization to nucleus (GO:0034504), regulation of hippo signaling (GO:0035330), cellular response to glucose starvation (GO:0042149), negative regulation of apoptotic process (GO:0043066)
GO Molecular Function (10): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)
GO Cellular Component (0):
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| protein kinase activity | 2 |
| phosphorylation | 1 |
| protein modification process | 1 |
| programmed cell death | 1 |
| apoptotic signaling pathway | 1 |
| execution phase of apoptosis | 1 |
| cytoskeleton organization | 1 |
| actin filament-based process | 1 |
| protein localization to organelle | 1 |
| hippo signaling | 1 |
| regulation of intracellular signal transduction | 1 |
| cellular response to starvation | 1 |
| apoptotic process | 1 |
| regulation of apoptotic process | 1 |
| negative regulation of programmed cell death | 1 |
| metal ion binding | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| kinase activity | 1 |
| phosphotransferase activity, alcohol group as acceptor | 1 |
| catalytic activity, acting on a protein | 1 |
| binding | 1 |
| transferase activity, transferring phosphorus-containing groups | 1 |
| catalytic activity | 1 |
| cation binding | 1 |
Protein interactions and networks
STRING
766 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| NUAK2 | SIK3 | Q9Y2K2 | 603 |
| NUAK2 | SIK2 | Q9H0K1 | 540 |
| NUAK2 | ARHGEF17 | Q96PE2 | 530 |
| NUAK2 | MPRIP | Q6WCQ1 | 498 |
| NUAK2 | SIK1 | P57059 | 474 |
| NUAK2 | A0A0B4J2F2 | A0A0B4J2F2 | 472 |
| NUAK2 | PTPN14 | Q15678 | 458 |
| NUAK2 | ACVR1 | Q04771 | 430 |
| NUAK2 | AMOTL2 | Q9Y2J4 | 427 |
| NUAK2 | CAB39 | Q9Y376 | 415 |
| NUAK2 | WDR49 | Q8IV35 | 408 |
| NUAK2 | PPP1R12A | O14974 | 407 |
| NUAK2 | PLEKHH3 | Q7Z736 | 399 |
| NUAK2 | XRN1 | Q8IZH2 | 389 |
| NUAK2 | PLA2G4C | Q9UP65 | 387 |
IntAct
20 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| TNIP1 | NFKB1 | psi-mi:“MI:0914”(association) | 0.790 |
| NUAK2 | PPP1R12A | psi-mi:“MI:0914”(association) | 0.640 |
| GRIPAP1 | NUAK2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| SFN | NUAK2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| NUAK2 | SMAD3 | psi-mi:“MI:0915”(physical association) | 0.520 |
| SMAD3 | NUAK2 | psi-mi:“MI:0915”(physical association) | 0.520 |
| YWHAE | NUAK2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| NUAK2 | SMAD2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| TGFBR1 | NUAK2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| NUAK2 | HSP90AB1 | psi-mi:“MI:0915”(physical association) | 0.400 |
| NUAK2 | HSP90AA1 | psi-mi:“MI:0914”(association) | 0.350 |
| NUAK2 | PPP1R12A | psi-mi:“MI:0914”(association) | 0.350 |
| NUAK2 | AP3D1 | psi-mi:“MI:0914”(association) | 0.350 |
| NUAK2 | GRIPAP1 | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (66): NUAK2 (Reconstituted Complex), HSP90AB3P (Affinity Capture-MS), LZTR1 (Affinity Capture-MS), PPP1R12A (Affinity Capture-MS), MARK3 (Affinity Capture-MS), UBXN7 (Affinity Capture-MS), FLNC (Affinity Capture-MS), BTRC (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), MARK2 (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), DCAF5 (Affinity Capture-MS), USP7 (Affinity Capture-MS), NUAK2 (Affinity Capture-RNA), NUAK2 (Two-hybrid)
ESM2 similar proteins: A0AUV4, A1A5Q6, A1A5R7, A2KF29, B1WAS2, C0HKC8, C0HKC9, D3ZML2, O60285, O74536, O88831, O88866, P41279, P51956, P57058, P97756, Q20443, Q2T9U5, Q5R7G9, Q5XHI9, Q60670, Q63562, Q641K5, Q66HE5, Q68UT7, Q6P431, Q6VZ17, Q7T0B0, Q7T0B1, Q7TNJ7, Q7TNL4, Q8BHI9, Q8BZN4, Q8C078, Q8C0N0, Q8C0V7, Q8C0X8, Q8CIP4, Q8IY84, Q8K4K4
Diamond homologs: A1Z9X0, A2CI34, A2CI35, A8KBH6, A8XW88, F1M7Y5, O70146, P00542, P00543, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P07332, P09215, P0CD62, P10102, P10829, P13678, P14238, P16054, P16879, P17252, P20444, P21137, P22612, P23298, P24723, P28867, P32866, P41743, P43057, P48562, P50527, P57078, P63318, P63319
SIGNOR signaling
5 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| STK11 | up-regulates | NUAK2 | phosphorylation |
| NUAK2 | down-regulates | LATS1 | phosphorylation |
| NUAK2 | “up-regulates activity” | WDR45 | phosphorylation |
| NUAK2 | “down-regulates activity” | PPP1R12A | phosphorylation |
| NUAK2 | “down-regulates activity” | LAT | phosphorylation |
Disease & clinical
Clinical variants and AI predictions
ClinVar
115 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 1 |
| Uncertain significance | 95 |
| Likely benign | 8 |
| Benign | 1 |
Top pathogenic / likely-pathogenic (2)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1184278 | NM_030952.3(NUAK2):c.412_433delinsG (p.Tyr138_Gln145delinsGlu) | Pathogenic |
| 3911831 | NM_030952.3(NUAK2):c.1666C>T (p.Gln556Ter) | Likely pathogenic |
SpliceAI
1143 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:205304509:GGCAT:G | acceptor_gain | 1.0000 |
| 1:205304510:GCAT:G | acceptor_gain | 1.0000 |
| 1:205304511:CAT:C | acceptor_gain | 1.0000 |
| 1:205304511:CATC:C | acceptor_gain | 1.0000 |
| 1:205304511:CATCT:C | acceptor_loss | 1.0000 |
| 1:205304512:AT:A | acceptor_gain | 1.0000 |
| 1:205304512:ATCTG:A | acceptor_loss | 1.0000 |
| 1:205304513:TCT:T | acceptor_loss | 1.0000 |
| 1:205304514:C:CA | acceptor_loss | 1.0000 |
| 1:205304514:C:CC | acceptor_gain | 1.0000 |
| 1:205304515:T:A | acceptor_loss | 1.0000 |
| 1:205304522:C:CT | acceptor_gain | 1.0000 |
| 1:205304523:A:T | acceptor_gain | 1.0000 |
| 1:205305193:A:AC | donor_gain | 1.0000 |
| 1:205305194:C:CC | donor_gain | 1.0000 |
| 1:205305196:CA:C | donor_loss | 1.0000 |
| 1:205305197:A:AC | donor_gain | 1.0000 |
| 1:205305197:AC:A | donor_gain | 1.0000 |
| 1:205305198:C:CT | donor_gain | 1.0000 |
| 1:205305198:CC:C | donor_gain | 1.0000 |
| 1:205305198:CCA:C | donor_gain | 1.0000 |
| 1:205305198:CCAG:C | donor_gain | 1.0000 |
| 1:205305198:CCAGA:C | donor_gain | 1.0000 |
| 1:205305327:TCCAC:T | acceptor_gain | 1.0000 |
| 1:205305328:CCACC:C | acceptor_gain | 1.0000 |
| 1:205305329:CAC:C | acceptor_gain | 1.0000 |
| 1:205305332:C:CC | acceptor_gain | 1.0000 |
| 1:205305332:C:CG | acceptor_loss | 1.0000 |
| 1:205306183:CTTA:C | donor_loss | 1.0000 |
| 1:205306184:TTACC:T | donor_loss | 1.0000 |
AlphaMissense
4085 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:205306299:G:C | D193E | 1.000 |
| 1:205306299:G:T | D193E | 1.000 |
| 1:205306300:T:A | D193V | 1.000 |
| 1:205306300:T:G | D193A | 1.000 |
| 1:205306301:C:G | D193H | 1.000 |
| 1:205308211:T:A | D175V | 1.000 |
| 1:205308211:T:G | D175A | 1.000 |
| 1:205308214:C:G | R174P | 1.000 |
| 1:205311814:C:A | K81N | 1.000 |
| 1:205311814:C:G | K81N | 1.000 |
| 1:205305272:A:C | F250L | 0.999 |
| 1:205305272:A:T | F250L | 0.999 |
| 1:205305274:A:G | F250L | 0.999 |
| 1:205305276:G:T | P249H | 0.999 |
| 1:205305322:A:G | W234R | 0.999 |
| 1:205305322:A:T | W234R | 0.999 |
| 1:205305328:C:G | D232H | 0.999 |
| 1:205306242:G:C | S212R | 0.999 |
| 1:205306242:G:T | S212R | 0.999 |
| 1:205306244:T:G | S212R | 0.999 |
| 1:205306246:C:T | G211E | 0.999 |
| 1:205306291:A:G | L196P | 0.999 |
| 1:205306300:T:C | D193G | 0.999 |
| 1:205306303:G:T | A192D | 0.999 |
| 1:205308195:G:C | N180K | 0.999 |
| 1:205308195:G:T | N180K | 0.999 |
| 1:205308210:A:C | D175E | 0.999 |
| 1:205308210:A:T | D175E | 0.999 |
| 1:205308211:T:C | D175G | 0.999 |
| 1:205311758:T:A | E100V | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000065722 (1:205314387 C>A,G), RS1000067557 (1:205315850 G>A,T), RS1000098269 (1:205316190 A>G), RS1000136971 (1:205315956 A>G), RS1000458589 (1:205303613 T>A,G), RS1000786912 (1:205304809 A>G), RS1000845560 (1:205321933 A>C), RS1001001055 (1:205301938 A>C), RS1001047192 (1:205302013 C>G), RS1001115106 (1:205308391 C>T), RS1001276124 (1:205322164 T>A,C), RS1001438335 (1:205310455 G>C,T), RS1001691733 (1:205313050 G>T), RS1001852357 (1:205306911 G>A), RS1002033654 (1:205311464 A>G)
Disease associations
OMIM: gene MIM:608131 | disease phenotypes: MIM:619452
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| anencephaly 2 | Moderate | Autosomal recessive |
Mondo (1): anencephaly 2 (MONDO:0030338)
Orphanet (0):
HPO phenotypes
9 total (9 of 9 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000161 | Median cleft upper lip |
| HP:0000528 | Anophthalmia |
| HP:0002323 | Anencephaly |
| HP:0003577 | Congenital onset |
| HP:0009099 | Median cleft palate |
| HP:0010289 | Cleft maxillary alveolar ridge |
| HP:0011803 | Bifid nose |
| HP:0012745 | Short palpebral fissure |
GWAS associations
10 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST005993_65 | Mean corpuscular hemoglobin | 1.000000e-10 |
| GCST010002_349 | Refractive error | 8.000000e-13 |
| GCST010143_9 | Meat-related diet | 4.000000e-11 |
| GCST010697_12 | Cortical surface area (min-P) | 6.000000e-10 |
| GCST010698_16 | Subcortical volume (min-P) | 8.000000e-09 |
| GCST010699_52 | Brain morphology (min-P) | 5.000000e-08 |
| GCST010700_66 | Cortical thickness (MOSTest) | 3.000000e-09 |
| GCST010701_17 | Cortical surface area (MOSTest) | 5.000000e-08 |
| GCST010702_2 | Subcortical volume (MOSTest) | 3.000000e-08 |
| GCST010703_27 | Brain morphology (MOSTest) | 5.000000e-09 |
EFO canonical traits (4, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004527 | mean corpuscular hemoglobin |
| EFO:0008111 | diet measurement |
| EFO:0004346 | neuroimaging measurement |
| EFO:0004840 | cortical thickness |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5698 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
34 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 330,942 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1287853 | FEDRATINIB | 4 | 3,554 |
| CHEMBL1289926 | AXITINIB | 4 | 15,732 |
| CHEMBL1789941 | RUXOLITINIB | 4 | 11,547 |
| CHEMBL180022 | NERATINIB | 4 | 9,404 |
| CHEMBL2103743 | TOFACITINIB CITRATE | 4 | 1,672 |
| CHEMBL221959 | TOFACITINIB | 4 | 10,408 |
| CHEMBL288441 | BOSUTINIB | 4 | 12,255 |
| CHEMBL502835 | NINTEDANIB | 4 | 8,545 |
| CHEMBL535 | SUNITINIB | 4 | 79,020 |
| CHEMBL601719 | CRIZOTINIB | 4 | 14,403 |
| CHEMBL608533 | MIDOSTAURIN | 4 | 7,259 |
| CHEMBL939 | GEFITINIB | 4 | 117,814 |
| CHEMBL270995 | BRIVANIB ALANINATE | 3 | 1,077 |
| CHEMBL300138 | ENZASTAURIN | 3 | 3,209 |
| CHEMBL3137331 | DEFACTINIB | 3 | 1,229 |
| CHEMBL3904602 | LEROCICLIB | 3 | 1,012 |
| CHEMBL428690 | ALVOCIDIB | 3 | 27,781 |
| CHEMBL522892 | DOVITINIB | 3 | 4,944 |
| CHEMBL603469 | LESTAURTINIB | 3 | |
| CHEMBL91829 | RUBOXISTAURIN | 3 | 77 |
| CHEMBL1721885 | SU-014813 | 2 | |
| CHEMBL3115681 | NARAZACICLIB | 2 | |
| CHEMBL402548 | DANUSERTIB | 2 | |
| CHEMBL475251 | R-406 | 2 | |
| CHEMBL572878 | TOZASERTIB | 2 | |
| CHEMBL575448 | BMS-754807 | 2 | |
| CHEMBL607707 | PELITINIB | 2 | |
| CHEMBL1908394 | GSK-461364 | 1 | |
| CHEMBL1908397 | KW-2449 | 1 | |
| CHEMBL296468 | BMS-387032 | 1 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — NuaK subfamily
Most potent curated ligand interactions (2 total), top 2:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| WZ4003 | Inhibition | 7.0 | pIC50 |
| HTH-02-006 | Inhibition | 6.9 | pIC50 |
Binding affinities (BindingDB)
11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| Staurosporine | KD | 1.7 nM |
| PKC-412 | KD | 190 nM |
| (3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril | KD | 520 nM |
| (18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione | KD | 700 nM |
| N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide | KD | 1100 nM |
| 5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide | KD | 2600 nM |
| 1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b | KD | 3100 nM |
| (E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide | KD | 3500 nM |
| N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide | KD | 3500 nM |
| 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile | KD | 5000 nM |
| 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one | KD | 5300 nM |
ChEMBL bioactivities
89 potent at pChembl≥5 of 90 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 10.07 | Kd | 0.086 | nM | STAUROSPORINE |
| 9.15 | Kd | 0.7 | nM | LEROCICLIB |
| 9.00 | Kd | 1 | nM | LESTAURTINIB |
| 8.92 | Kd | 1.2 | nM | TAE-684 |
| 8.79 | IC50 | 1.62 | nM | STAUROSPORINE |
| 8.78 | IC50 | 1.67 | nM | STAUROSPORINE |
| 8.72 | IC50 | 1.9 | nM | STAUROSPORINE |
| 8.52 | Kd | 3 | nM | BRIVANIB ALANINATE |
| 8.46 | Kd | 3.5 | nM | CHEMBL4284499 |
| 8.30 | IC50 | 5.012 | nM | NARAZACICLIB |
| 8.15 | Kd | 7 | nM | CYC-116 |
| 8.00 | Kd | 10 | nM | CHEMBL4465866 |
| 8.00 | Kd | 10 | nM | CHEMBL1229592 |
| 7.96 | Kd | 11 | nM | CHEMBL4576489 |
| 7.80 | IC50 | 15.85 | nM | CHEMBL6175168 |
| 7.68 | Kd | 21 | nM | NINTEDANIB |
| 7.64 | Kd | 23 | nM | GSK-461364 |
| 7.62 | Kd | 24 | nM | PF-03814735 |
| 7.60 | Kd | 25 | nM | DANUSERTIB |
| 7.60 | IC50 | 25.12 | nM | CHEMBL190684 |
| 7.60 | IC50 | 25.12 | nM | CHEMBL6177408 |
| 7.58 | Kd | 26 | nM | JNJ-7706621 |
| 7.40 | IC50 | 39.81 | nM | CHEMBL6167301 |
| 7.31 | Kd | 49 | nM | FEDRATINIB |
| 7.27 | Kd | 54 | nM | KW-2449 |
| 7.20 | Kd | 63 | nM | MIDOSTAURIN |
| 7.20 | IC50 | 63.1 | nM | CHEMBL6177133 |
| 7.19 | Kd | 65 | nM | R-406 |
| 7.14 | Kd | 72 | nM | LESTAURTINIB |
| 7.07 | Kd | 86 | nM | GSK-690693 |
| 7.00 | IC50 | 100 | nM | CHEMBL4303523 |
| 7.00 | IC50 | 100 | nM | CHEMBL6163620 |
| 6.92 | IC50 | 120 | nM | CHEMBL5199998 |
| 6.92 | Kd | 120 | nM | CRIZOTINIB |
| 6.90 | IC50 | 126 | nM | CHEMBL5202966 |
| 6.90 | IC50 | 125.9 | nM | CHEMBL6170125 |
| 6.89 | Kd | 130 | nM | DOVITINIB |
| 6.89 | Kd | 130 | nM | CHEMBL1908395 |
| 6.85 | Kd | 140 | nM | NERATINIB |
| 6.82 | Kd | 150 | nM | SUNITINIB |
| 6.66 | Kd | 220 | nM | BOSUTINIB |
| 6.62 | Kd | 240 | nM | TOFACITINIB CITRATE |
| 6.62 | Kd | 240 | nM | TOFACITINIB |
| 6.50 | Kd | 320 | nM | RUBOXISTAURIN |
| 6.50 | Kd | 320 | nM | RUXOLITINIB |
| 6.40 | Kd | 400 | nM | SU-014813 |
| 6.38 | Kd | 420 | nM | TOFACITINIB CITRATE |
| 6.38 | Kd | 420 | nM | TOFACITINIB |
| 6.36 | Kd | 440 | nM | CGP-52421 |
| 6.34 | Kd | 454 | nM | DEFACTINIB |
PubChem BioAssay actives
74 with measured affinity, of 551 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| (2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one | 435559: Binding constant for SNARK kinase domain | kd | 0.0001 | uM |
| 4-[[5-(4-propan-2-ylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one | 1609450: Binding affinity to SNARK (unknown origin) | kd | 0.0007 | uM |
| (15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one | 508088: Binding affinity to SNARK | kd | 0.0010 | uM |
| 5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine | 1845591: Binding affinity to NUAK2 (unknown origin) assessed as dissociation constant | kd | 0.0012 | uM |
| [(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-yl] (2S)-2-aminopropanoate | 1425095: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0030 | uM |
| 9-(cyclohexylmethyl)-4,5-dimethoxy-9,14,16-triazatetracyclo[8.7.0.02,7.011,15]heptadeca-1(17),2,4,6,10,12,15-heptaen-8-one | 1415053: Binding affinity to DNA-tagged recombinant human SNARK (22 to 333 residues) expressed in mammalian expression system by KINOMEscan assay | kd | 0.0035 | uM |
| 4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine | 1425095: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0070 | uM |
| 3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide | 1526222: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged NUAK2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay | kd | 0.0100 | uM |
| N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide | 2185074: Binding affinity to SNARK (unknown origin) assessed as dissociation constant | kd | 0.0100 | uM |
| 3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide | 1526222: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged NUAK2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay | kd | 0.0110 | uM |
| methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate | 625139: Binding constant for SNARK kinase domain | kd | 0.0210 | uM |
| 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide | 1845591: Binding affinity to NUAK2 (unknown origin) assessed as dissociation constant | kd | 0.0230 | uM |
| N-[2-[4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide | 1425095: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0240 | uM |
| N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide | 1425095: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0250 | uM |
| 4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide | 435559: Binding constant for SNARK kinase domain | kd | 0.0260 | uM |
| Fedratinib | 625139: Binding constant for SNARK kinase domain | kd | 0.0490 | uM |
| [4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone | 625139: Binding constant for SNARK kinase domain | kd | 0.0540 | uM |
| Midostaurin | 435559: Binding constant for SNARK kinase domain | kd | 0.0630 | uM |
| 6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one | 625139: Binding constant for SNARK kinase domain | kd | 0.0650 | uM |
| 4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol | 625139: Binding constant for SNARK kinase domain | kd | 0.0860 | uM |
| N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]propanamide | 1845578: Inhibition of N-terminal GST-tagged human NUAK2 expressed in Escherichia coli DH5alpha incubated for 30 mins in presence of gamma-[32P]ATP by cerenkov counting analysis | ic50 | 0.1000 | uM |
| Crizotinib | 625139: Binding constant for SNARK kinase domain | kd | 0.1200 | uM |
| 7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-2-methylsulfonylpyrrolo[2,3-d]pyrimidin-6-one | 1845564: Inhibition of NUAK2 (unknown origin) | ic50 | 0.1200 | uM |
| N-[3-[5-iodo-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]butanamide | 1845564: Inhibition of NUAK2 (unknown origin) | ic50 | 0.1260 | uM |
| 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one | 435559: Binding constant for SNARK kinase domain | kd | 0.1300 | uM |
| 5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride | 625139: Binding constant for SNARK kinase domain | kd | 0.1300 | uM |
| Neratinib | 625139: Binding constant for SNARK kinase domain | kd | 0.1400 | uM |
| Sunitinib | 435559: Binding constant for SNARK kinase domain | kd | 0.1500 | uM |
| Bosutinib | 625139: Binding constant for SNARK kinase domain | kd | 0.2200 | uM |
| Tofacitinib | 625139: Binding constant for SNARK kinase domain | kd | 0.2400 | uM |
| (18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione | 435559: Binding constant for SNARK kinase domain | kd | 0.3200 | uM |
| Ruxolitinib | 625139: Binding constant for SNARK kinase domain | kd | 0.3200 | uM |
| 5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide | 435559: Binding constant for SNARK kinase domain | kd | 0.4000 | uM |
| N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide | 508088: Binding affinity to SNARK | kd | 0.4400 | uM |
| N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide | 1425095: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.4540 | uM |
| N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide | 435559: Binding constant for SNARK kinase domain | kd | 0.5300 | uM |
| 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide | 1425095: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.7050 | uM |
| N-[3-[[5-bromo-4-[(4-sulfamoylphenyl)methylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide | 1823799: Inhibition of full length recombinant human NUAK2 using KKKVSRSGLYRSPSMPENLNRPR as substrate incubated for 40 mins in presence of [gamma-33P-ATP] by radiometric scintillation assay | ic50 | 0.9000 | uM |
| (3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one | 625139: Binding constant for SNARK kinase domain | kd | 0.9100 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148895: Binding affinity to human NUAK2 incubated for 45 mins by Kinobead based pull down assay | kd | 1.0108 | uM |
| 4-[[[5-bromo-2-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]amino]methyl]benzenesulfonamide | 1823799: Inhibition of full length recombinant human NUAK2 using KKKVSRSGLYRSPSMPENLNRPR as substrate incubated for 40 mins in presence of [gamma-33P-ATP] by radiometric scintillation assay | ic50 | 1.1510 | uM |
| Axitinib | 625139: Binding constant for SNARK kinase domain | kd | 1.3000 | uM |
| 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one | 435559: Binding constant for SNARK kinase domain | kd | 1.4000 | uM |
| N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide | 435559: Binding constant for SNARK kinase domain | kd | 1.7000 | uM |
| (2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide | 2167411: Binding affinity to NUAK2 (unknown origin) by phage based competition assay | kd | 1.8000 | uM |
| N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide | 1845564: Inhibition of NUAK2 (unknown origin) | ic50 | 2.6000 | uM |
| (4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone | 769495: Binding affinity to SNARK (unknown origin) | kd | 2.6000 | uM |
| (E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide | 435559: Binding constant for SNARK kinase domain | kd | 2.7000 | uM |
| 2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol | 625139: Binding constant for SNARK kinase domain | kd | 3.6000 | uM |
| 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione | 625139: Binding constant for SNARK kinase domain | kd | 4.1000 | uM |
CTD chemical–gene interactions
50 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects expression, decreases expression | 3 |
| perfluorooctane sulfonic acid | decreases expression, increases expression | 2 |
| Arsenic | affects expression, affects methylation | 2 |
| Methotrexate | affects cotreatment, increases expression, decreases expression | 2 |
| Silicon Dioxide | decreases methylation, increases expression | 2 |
| Silver | increases expression | 2 |
| Cyclosporine | decreases expression, increases expression | 2 |
| Aflatoxin B1 | decreases methylation, increases expression | 2 |
| aristolochic acid I | increases expression | 1 |
| Glupearl 19S | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| bisphenol A | decreases expression | 1 |
| titanium dioxide | decreases methylation | 1 |
| salinomycin | decreases expression | 1 |
| quercitrin | decreases expression | 1 |
| trichostatin A | decreases expression | 1 |
| sodium arsenite | increases expression | 1 |
| zinc chromate | decreases expression, increases abundance | 1 |
| potassium chromate(VI) | decreases expression | 1 |
| S-(1,2-dichlorovinyl)cysteine | affects response to substance, increases expression, affects cotreatment, decreases expression | 1 |
| polyhexamethyleneguanidine | affects expression | 1 |
| chromium hexavalent ion | decreases expression, increases abundance | 1 |
| CGP 52608 | increases reaction, affects binding | 1 |
| 2-palmitoylglycerol | increases expression | 1 |
| abrine | increases expression | 1 |
| jinfukang | decreases expression, increases reaction | 1 |
| WZ4003 | decreases activity | 1 |
| Temozolomide | increases expression | 1 |
| Sunitinib | increases expression | 1 |
| Arsenic Trioxide | increases expression | 1 |
ChEMBL screening assays
200 unique, capped per target: 200 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1017050 | Binding | Binding affinity to SNARK | Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Associated diseases: anencephaly 2
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): anencephaly 2