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GeneBe

RIPK3

receptor interacting serine/threonine kinase 3

Basic information

Region (hg38): 14:24336024-24340022

Links

ENSG00000129465NCBI:11035OMIM:605817HGNC:10021Uniprot:Q9Y572AlphaFoldGenCCjaxSfariGnomADPubmed

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIPK3 gene.

  • 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)link
14-24336371-T-C Inborn genetic diseases Uncertain significance (May 24, 2023)link
14-24336905-G-A Inborn genetic diseases Uncertain significance (Jul 06, 2021)link
14-24336920-C-G Inborn genetic diseases Uncertain significance (Apr 07, 2022)link
14-24337096-C-T Inborn genetic diseases Likely benign (Feb 28, 2023)link
14-24337154-T-G Inborn genetic diseases Likely benign (May 18, 2023)link
14-24337279-A-G Inborn genetic diseases Uncertain significance (Nov 09, 2022)link
14-24337333-A-G Inborn genetic diseases Uncertain significance (Jun 30, 2023)link
14-24337403-A-G Inborn genetic diseases Likely benign (Feb 22, 2023)link
14-24337408-G-A not specified Uncertain significance (Jun 11, 2015)link
14-24337945-C-A Inborn genetic diseases Uncertain significance (Mar 06, 2023)link
14-24337989-C-T Inborn genetic diseases Uncertain significance (Apr 07, 2023)link
14-24338429-C-T Inborn genetic diseases Conflicting interpretations of pathogenicity (Jul 13, 2021)link
14-24338510-C-T Inborn genetic diseases Likely benign (Oct 26, 2021)link
14-24338516-C-G Inborn genetic diseases Uncertain significance (Apr 25, 2022)link
14-24339233-C-T Inborn genetic diseases Uncertain significance (Feb 28, 2023)link
14-24339319-G-T Inborn genetic diseases Uncertain significance (Aug 23, 2021)link
14-24339472-A-G Inborn genetic diseases Uncertain significance (Dec 03, 2021)link
14-24339539-C-G Inborn genetic diseases Uncertain significance (Aug 16, 2022)link

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RIPK3protein_codingprotein_codingENST00000216274 104025
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.19e-140.02241256930551257480.000219
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.01643003010.9970.00001653348
Missense in Polyphen7589.7830.835351047
Synonymous0.7931161270.9110.000007871051
Loss of Function0.1902223.00.9579.92e-7260

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006510.000651
Ashkenazi Jewish0.000.00
East Asian0.0002180.000217
Finnish0.00009240.0000924
European (Non-Finnish)0.0001770.000176
Middle Eastern0.0002180.000217
South Asian0.0003590.000327
Other0.0001630.000163

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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