RIPK2
receptor interacting serine/threonine kinase 2, the group of Caspase recruitment domain containing
Basic information
Region (hg38): 8:89757806-89791064
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIPK2 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 | 2 | |||||
| missense | 27 | 30 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 2 | 2 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 27 | 3 | 2 |
Variants in RIPK2
This is a list of pathogenic ClinVar variants found in the RIPK2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-89758206-T-G | not specified | Uncertain significance (Nov 06, 2023) | ||
| 8-89762924-T-G | not specified | Uncertain significance (Sep 29, 2023) | ||
| 8-89762955-T-C | Likely benign (Aug 22, 2018) | |||
| 8-89762965-A-G | Uncertain significance (Feb 01, 2023) | |||
| 8-89765389-C-T | not specified | Uncertain significance (Oct 08, 2024) | ||
| 8-89765483-A-G | not specified | Uncertain significance (Nov 18, 2023) | ||
| 8-89766285-G-A | Leprosy, susceptibility to, 1 | Uncertain risk allele (Jun 10, 2022) | ||
| 8-89769793-A-G | not specified | Uncertain significance (Oct 01, 2024) | ||
| 8-89769800-G-A | not specified | Uncertain significance (Jul 09, 2021) | ||
| 8-89769802-A-G | not specified | Uncertain significance (Aug 01, 2022) | ||
| 8-89769803-T-C | not specified | Uncertain significance (Jan 08, 2024) | ||
| 8-89769900-A-T | Benign (May 31, 2018) | |||
| 8-89772756-C-T | not specified | Uncertain significance (Sep 09, 2024) | ||
| 8-89772762-G-A | not specified | Uncertain significance (Apr 22, 2022) | ||
| 8-89772765-C-T | not specified | Uncertain significance (Dec 04, 2024) | ||
| 8-89772766-G-A | not specified | Likely benign (Jun 09, 2022) | ||
| 8-89772777-C-G | Benign (Feb 26, 2018) | |||
| 8-89772790-G-A | not specified | Uncertain significance (Feb 11, 2022) | ||
| 8-89780141-T-C | not specified | Uncertain significance (Jun 07, 2024) | ||
| 8-89780156-C-T | not specified | Uncertain significance (Feb 15, 2023) | ||
| 8-89784119-G-A | not specified | Uncertain significance (Nov 29, 2023) | ||
| 8-89784141-TAAA-T | not specified | Benign (Mar 28, 2016) | ||
| 8-89784141-T-TA | Benign (Jan 08, 2024) | |||
| 8-89786627-G-C | not specified | Uncertain significance (Dec 28, 2022) | ||
| 8-89786674-G-A | not specified | Uncertain significance (Oct 11, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RIPK2 | protein_coding | protein_coding | ENST00000220751 | 11 | 33317 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.393 | 0.607 | 125646 | 0 | 6 | 125652 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.16 | 172 | 272 | 0.632 | 0.0000127 | 3518 |
| Missense in Polyphen | 41 | 120.54 | 0.34014 | 1569 | ||
| Synonymous | 1.20 | 81 | 95.9 | 0.845 | 0.00000445 | 1010 |
| Loss of Function | 3.73 | 6 | 26.8 | 0.224 | 0.00000138 | 345 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000325 | 0.0000325 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000274 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000658 | 0.0000654 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation. {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730}.;
- Pathway
- Neurotrophin signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Shigellosis - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway;Apoptosis-related network due to altered Notch3 in ovarian cancer;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;T-Cell antigen Receptor (TCR) Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Signaling by Interleukins;p75NTR signals via NF-kB;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Downstream TCR signaling;TCR signaling;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Post-translational protein modification;Metabolism of proteins;Interleukin-1 signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;fas signaling pathway (cd95);IL-7 signaling;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;activated TAK1 mediates p38 MAPK activation;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;Ovarian tumor domain proteases;Deubiquitination;p75NTR recruits signalling complexes;EPO signaling;Death Receptor Signalling;p75 NTR receptor-mediated signalling;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;VEGF;Canonical NF-kappaB pathway;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;p75(NTR)-mediated signaling;IL12-mediated signaling events;Interleukin-1 family signaling
(Consensus)
Recessive Scores
- pRec
- 0.232
Intolerance Scores
- loftool
- 0.490
- rvis_EVS
- 0.42
- rvis_percentile_EVS
- 76.96
Haploinsufficiency Scores
- pHI
- 0.217
- hipred
- Y
- hipred_score
- 0.792
- ghis
- 0.421
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.918
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ripk2
- Phenotype
- hematopoietic system phenotype; immune system phenotype; digestive/alimentary phenotype;
Gene ontology
- Biological process
- MAPK cascade;activation of MAPK activity;positive regulation of cytokine-mediated signaling pathway;adaptive immune response;apoptotic process;inflammatory response;signal transduction;I-kappaB kinase/NF-kappaB signaling;JNK cascade;activation of JNKK activity;activation of JUN kinase activity;positive regulation of peptidyl-threonine phosphorylation;positive regulation of cell death;peptidyl-tyrosine phosphorylation;positive regulation of protein ubiquitination;lipopolysaccharide-mediated signaling pathway;positive regulation of protein binding;positive regulation of chemokine production;positive regulation of interferon-alpha production;positive regulation of interferon-beta production;positive regulation of interferon-gamma production;positive regulation of interleukin-12 production;positive regulation of interleukin-2 production;positive regulation of interleukin-6 production;positive regulation of tumor necrosis factor production;positive regulation of immature T cell proliferation;positive regulation of peptidyl-serine phosphorylation;toll-like receptor 2 signaling pathway;toll-like receptor 4 signaling pathway;T cell proliferation;positive regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to exogenous dsRNA;innate immune response;positive regulation of T-helper 1 cell differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of alpha-beta T cell proliferation;positive regulation of interleukin-1 beta secretion;positive regulation of peptidyl-tyrosine phosphorylation;defense response to Gram-positive bacterium;T cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;positive regulation of ERK1 and ERK2 cascade;nucleotide-binding oligomerization domain containing signaling pathway;nucleotide-binding oligomerization domain containing 1 signaling pathway;nucleotide-binding oligomerization domain containing 2 signaling pathway;interleukin-1-mediated signaling pathway;response to interleukin-12;response to interleukin-18;cellular response to lipoteichoic acid;cellular response to peptidoglycan;cellular response to muramyl dipeptide;activation of cysteine-type endopeptidase activity;positive regulation of xenophagy
- Cellular component
- cytoplasm;cytosol;cytoskeleton;vesicle;protein-containing complex
- Molecular function
- protein serine/threonine kinase activity;JUN kinase kinase kinase activity;non-membrane spanning protein tyrosine kinase activity;signaling receptor binding;protein binding;ATP binding;LIM domain binding;identical protein binding;protein homodimerization activity;CARD domain binding;caspase binding