RIPK3
receptor interacting serine/threonine kinase 3
Basic information
Region (hg38): 14:24336024-24340022
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (10 variants)
- not specified (1 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIPK3 gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 9 | 2 | 11 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice variant | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 9 | 2 | 0 |
Variants in RIPK3
This is a list of pathogenic ClinVar variants found in the RIPK3 region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-24336285-C-T | Inborn genetic diseases | Uncertain significance (Jul 26, 2022) | ||
| 14-24336371-T-C | Inborn genetic diseases | Uncertain significance (May 24, 2023) | ||
| 14-24336905-G-A | Inborn genetic diseases | Uncertain significance (Jul 06, 2021) | ||
| 14-24336920-C-G | Inborn genetic diseases | Uncertain significance (Apr 07, 2022) | ||
| 14-24337096-C-T | Inborn genetic diseases | Likely benign (Feb 28, 2023) | ||
| 14-24337154-T-G | Inborn genetic diseases | Likely benign (May 18, 2023) | ||
| 14-24337279-A-G | Inborn genetic diseases | Uncertain significance (Nov 09, 2022) | ||
| 14-24337333-A-G | Inborn genetic diseases | Uncertain significance (Jun 30, 2023) | ||
| 14-24337403-A-G | Inborn genetic diseases | Likely benign (Feb 22, 2023) | ||
| 14-24337408-G-A | not specified | Uncertain significance (Jun 11, 2015) | ||
| 14-24337945-C-A | Inborn genetic diseases | Uncertain significance (Mar 06, 2023) | ||
| 14-24337989-C-T | Inborn genetic diseases | Uncertain significance (Apr 07, 2023) | ||
| 14-24338429-C-T | Inborn genetic diseases | Conflicting interpretations of pathogenicity (Jul 13, 2021) | ||
| 14-24338510-C-T | Inborn genetic diseases | Likely benign (Oct 26, 2021) | ||
| 14-24338516-C-G | Inborn genetic diseases | Uncertain significance (Apr 25, 2022) | ||
| 14-24339233-C-T | Inborn genetic diseases | Uncertain significance (Feb 28, 2023) | ||
| 14-24339319-G-T | Inborn genetic diseases | Uncertain significance (Aug 23, 2021) | ||
| 14-24339472-A-G | Inborn genetic diseases | Uncertain significance (Dec 03, 2021) | ||
| 14-24339539-C-G | Inborn genetic diseases | Uncertain significance (Aug 16, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RIPK3 | protein_coding | protein_coding | ENST00000216274 | 10 | 4025 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.19e-14 | 0.0224 | 125693 | 0 | 55 | 125748 | 0.000219 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0164 | 300 | 301 | 0.997 | 0.0000165 | 3348 |
| Missense in Polyphen | 75 | 89.783 | 0.83535 | 1047 | ||
| Synonymous | 0.793 | 116 | 127 | 0.911 | 0.00000787 | 1051 |
| Loss of Function | 0.190 | 22 | 23.0 | 0.957 | 9.92e-7 | 260 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000651 | 0.000651 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000218 | 0.000217 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000177 | 0.000176 |
| Middle Eastern | 0.000218 | 0.000217 |
| South Asian | 0.000359 | 0.000327 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production. {ECO:0000269|PubMed:19498109, ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513, ECO:0000269|PubMed:22265413, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:22421439, ECO:0000269|PubMed:29883609}.;
- Pathway
- TNF signaling pathway - Homo sapiens (human);Cytosolic DNA-sensing pathway - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);TNF alpha Signaling Pathway;Nanoparticle triggered regulated necrosis;TICAM1, RIP1-mediated IKK complex recruitment ;Toll Like Receptor 3 (TLR3) Cascade;ZBP1(DAI) mediated induction of type I IFNs;Toll-Like Receptors Cascades;Innate Immune System;Immune System;Regulated Necrosis;Programmed Cell Death;RIPK1-mediated regulated necrosis;RIP-mediated NFkB activation via ZBP1;IL-7 signaling;TLR3-mediated TICAM1-dependent programmed cell death;JAK STAT pathway and regulation;EPO signaling;TNFalpha;Cytosolic sensors of pathogen-associated DNA ;IKK complex recruitment mediated by RIP1;TRIF-mediated programmed cell death;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;VEGF
(Consensus)
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- loftool
- 0.810
- rvis_EVS
- -0.04
- rvis_percentile_EVS
- 50.45
Haploinsufficiency Scores
- pHI
- 0.0492
- hipred
- N
- hipred_score
- 0.313
- ghis
- 0.502
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ripk3
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland 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); embryo phenotype; immune system phenotype; digestive/alimentary phenotype; hematopoietic system 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); normal 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); liver/biliary system phenotype;
Gene ontology
- Biological process
- regulation of T cell mediated cytotoxicity;regulation of adaptive immune response;cellular protein modification process;signal transduction;I-kappaB kinase/NF-kappaB signaling;positive regulation of phosphatase activity;activation of protein kinase activity;regulation of interferon-gamma production;T cell differentiation in thymus;NIK/NF-kappaB signaling;T cell homeostasis;regulation of activated T cell proliferation;protein autophosphorylation;lymph node development;spleen development;thymus development;positive regulation of NF-kappaB transcription factor activity;protein homooligomerization;protein heterooligomerization;positive regulation of ligase activity;positive regulation of oxidoreductase activity;positive regulation of necroptotic process;regulation of activation-induced cell death of T cells;necroptotic process;apoptotic signaling pathway;positive regulation of nucleic acid-templated transcription;amyloid fibril formation;positive regulation of reactive oxygen species metabolic process;regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation;positive regulation of intrinsic apoptotic signaling pathway
- Cellular component
- mitochondrion;cytosol;plasma membrane
- Molecular function
- transcription coactivator activity;protein kinase activity;protein serine/threonine kinase activity;NF-kappaB-inducing kinase activity;protein binding;ATP binding;identical protein binding;protein-containing complex binding