CHUK
component of inhibitor of nuclear factor kappa B kinase complex, the group of I kappa B kinases|IKK complex
Basic information
Region (hg38): 10:100188300-100229596
Previous symbols: [ "TCF16" ]
Links
Phenotypes
GenCC
Source:
- cocoon syndrome (Definitive), mode of inheritance: AR
- cocoon syndrome (Strong), mode of inheritance: AR
- cocoon syndrome (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Fetal encasement syndrome (Cocoon syndrome); Bartsocas-Papas syndrome 2 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal | 20961246; 25691407 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHUK gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 43 | 48 | ||||
| missense | 52 | 59 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 4 | 8 | 12 | |||
| non coding | 33 | 34 | 69 | |||
| Total | 2 | 0 | 54 | 81 | 41 |
Variants in CHUK
This is a list of pathogenic ClinVar variants found in the CHUK region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 10-100189605-G-A | Uncertain significance (Aug 31, 2022) | |||
| 10-100189635-C-G | Likely benign (Dec 31, 2022) | |||
| 10-100189638-G-C | Uncertain significance (Apr 02, 2023) | |||
| 10-100189674-T-G | Benign (May 11, 2021) | |||
| 10-100189834-C-CT | Benign (May 11, 2021) | |||
| 10-100190872-C-A | Inborn genetic diseases | Uncertain significance (May 21, 2024) | ||
| 10-100190879-T-C | Likely benign (Jan 08, 2024) | |||
| 10-100190902-A-G | Likely benign (Feb 19, 2022) | |||
| 10-100190937-A-G | Likely benign (Dec 06, 2023) | |||
| 10-100190982-G-A | Likely benign (Oct 05, 2023) | |||
| 10-100190985-C-A | Likely benign (Apr 24, 2023) | |||
| 10-100193280-G-A | Likely benign (Dec 12, 2022) | |||
| 10-100193284-C-G | Likely benign (Mar 20, 2023) | |||
| 10-100193320-A-G | Uncertain significance (Sep 28, 2022) | |||
| 10-100193326-G-A | Likely benign (Dec 02, 2023) | |||
| 10-100193351-C-T | Likely benign (May 20, 2023) | |||
| 10-100193352-G-A | Uncertain significance (Sep 20, 2022) | |||
| 10-100193400-G-C | Uncertain significance (Jul 26, 2022) | |||
| 10-100193405-T-C | Likely benign (Sep 01, 2022) | |||
| 10-100193518-C-G | Benign (May 11, 2021) | |||
| 10-100193524-C-T | Benign (May 11, 2021) | |||
| 10-100193568-A-G | Benign (May 11, 2021) | |||
| 10-100193948-A-C | not specified | Benign (Jan 24, 2024) | ||
| 10-100193976-T-C | Likely benign (Apr 15, 2023) | |||
| 10-100194000-A-C | Uncertain significance (Jan 27, 2017) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CHUK | protein_coding | protein_coding | ENST00000370397 | 21 | 41322 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.994 | 0.00597 | 125728 | 0 | 18 | 125746 | 0.0000716 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.78 | 242 | 398 | 0.608 | 0.0000195 | 4921 |
| Missense in Polyphen | 56 | 145.14 | 0.38582 | 1830 | ||
| Synonymous | 0.933 | 117 | 131 | 0.896 | 0.00000596 | 1334 |
| Loss of Function | 5.34 | 7 | 46.1 | 0.152 | 0.00000228 | 564 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000907 | 0.0000906 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.000106 | 0.000105 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa- B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). {ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415}.;
- Disease
- DISEASE: Cocoon syndrome (COCOS) [MIM:613630]: A lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. {ECO:0000269|PubMed:20961246}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Cytosolic DNA-sensing pathway - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Nucleotide-binding Oligomerization Domain (NOD) pathway;Osteopontin Signaling;Regulation of toll-like receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;IL-1 signaling pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Leptin signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;B Cell Receptor Signaling Pathway;TNF alpha Signaling Pathway;AGE-RAGE pathway;Interleukin-11 Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Apoptosis;JAK-STAT;EBV LMP1 signaling;Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;Hair Follicle Development- Induction (Part 1 of 3);NLR Proteins;Rac1-Pak1-p38-MMP-2 pathway;Photodynamic therapy-induced NF-kB survival signaling;Apoptotic Signaling Pathway;MAPK Signaling Pathway;Canonical and Non-canonical Notch signaling;MAPK and NFkB Signalling Pathways Inhibited by Yersinia YopJ;Toll-like Receptor Signaling;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;RIG-I-like Receptor Signaling;IL-4 Signaling Pathway;Chemokine signaling pathway;Fibrin Complement Receptor 3 Signaling Pathway;PI3K-Akt Signaling Pathway;Ras Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;Estrogen signaling pathway;Toll-like Receptor Signaling Pathway;RAGE;TLR NFkB;Toll Like Receptor 7/8 (TLR7/8) Cascade;double stranded rna induced gene expression;Interleukin-17 signaling;Disease;Signal Transduction;Signaling by Interleukins;influence of ras and rho proteins on g1 to s transition;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;chaperones modulate interferon signaling pathway;trefoil factors initiate mucosal healing;akt signaling pathway;ras signaling pathway;hiv-1 nef: negative effector of fas and tnf;signal transduction through il1r;tnf/stress related signaling;nf-kb signaling pathway;nfkb activation by nontypeable hemophilus influenzae;keratinocyte differentiation;toll-like receptor pathway;mapkinase signaling pathway;NIK-->noncanonical NF-kB signaling;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;TICAM1, RIP1-mediated IKK complex recruitment ;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;B cell receptor signaling;ZBP1(DAI) mediated induction of type I IFNs;Toll-Like Receptors Cascades;Downstream TCR signaling;TCR signaling;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Activation of NF-kappaB in B cells;Signaling by the B Cell Receptor (BCR);Interleukin-1 signaling;Dectin-1 mediated noncanonical NF-kB signaling;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Fc epsilon receptor (FCERI) signaling;TCR;IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation;Innate Immune System;Immune System;Adaptive Immune System;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Downstream signaling events of B Cell Receptor (BCR);BCR;IL-1 NFkB;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;ceramide signaling pathway;IL1;RIP-mediated NFkB activation via ZBP1;IL-7 signaling;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;MAP3K8 (TPL2)-dependent MAPK1/3 activation;TNFR1-induced NFkappaB signaling pathway;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;TNF signaling;MyD88 dependent cascade initiated on endosome;Validated transcriptional targets of TAp63 isoforms;BCR signaling pathway;bone remodeling;PIP3 activates AKT signaling;JAK STAT pathway and regulation;IL11;EPO signaling;Death Receptor Signalling;Regulation of TNFR1 signaling;IL4;Leptin;FCERI mediated NF-kB activation;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;ER-Phagosome pathway;TNFalpha;Cytosolic sensors of pathogen-associated DNA ;IKK complex recruitment mediated by RIP1;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;AKT phosphorylates targets in the cytosol;VEGF;Canonical NF-kappaB pathway;Intracellular signaling by second messengers;IRAK1 recruits IKK complex;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;RANKL;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Osteopontin-mediated events;HIV-1 Nef: Negative effector of Fas and TNF-alpha;TRAIL signaling pathway;TNF receptor signaling pathway ;Diseases of signal transduction;Validated nuclear estrogen receptor alpha network;Fc-epsilon receptor I signaling in mast cells;Endogenous TLR signaling;TCR signaling in naïve CD8+ T cells;p75(NTR)-mediated signaling;FAS (CD95) signaling pathway;FoxO family signaling;Class I PI3K signaling events mediated by Akt;IL1-mediated signaling events;Alternative NF-kappaB pathway;TCR signaling in naïve CD4+ T cells;Interleukin-1 family signaling;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.634
Intolerance Scores
- loftool
- 0.345
- rvis_EVS
- -0.2
- rvis_percentile_EVS
- 38.98
Haploinsufficiency Scores
- pHI
- 0.841
- hipred
- Y
- hipred_score
- 0.774
- ghis
- 0.595
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.727
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Chuk
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); reproductive system phenotype; neoplasm; embryo phenotype;
Zebrafish Information Network
- Gene name
- chuk
- Affected structure
- DEL
- Phenotype tag
- abnormal
- Phenotype quality
- decreased area
Gene ontology
- Biological process
- stimulatory C-type lectin receptor signaling pathway;antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent;MyD88-independent toll-like receptor signaling pathway;skeletal muscle contraction;protein phosphorylation;inflammatory response;immune response;I-kappaB kinase/NF-kappaB signaling;I-kappaB phosphorylation;Rho protein signal transduction;response to virus;response to toxic substance;anatomical structure morphogenesis;response to acetate;regulation of tumor necrosis factor-mediated signaling pathway;peptidyl-serine phosphorylation;negative regulation of NF-kappaB transcription factor activity;response to lipopolysaccharide;response to hydroperoxide;tumor necrosis factor-mediated signaling pathway;cellular response to reactive oxygen species;TRIF-dependent toll-like receptor signaling pathway;NIK/NF-kappaB signaling;Fc-epsilon receptor signaling pathway;response to drug;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to amino acid;innate immune response;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;T cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;striated muscle cell differentiation;stress-activated MAPK cascade;interleukin-1-mediated signaling pathway;cellular response to cadmium ion;cellular response to tumor necrosis factor;cellular response to virus;positive regulation of interferon-alpha secretion
- Cellular component
- nucleoplasm;cytoplasm;cytosol;IkappaB kinase complex;cytoplasmic side of plasma membrane;CD40 receptor complex;intracellular membrane-bounded organelle
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;IkappaB kinase activity;protein homodimerization activity;protein heterodimerization activity;scaffold protein binding