RIPK3

receptor interacting serine/threonine kinase 3

Basic information

Region (hg38): 14:24336024-24340022

Links

ENSG00000129465 ∙ NCBI:11035 ∙ OMIM:605817 ∙ HGNC:10021 ∙ Uniprot:Q9Y572 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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 (18 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.

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						0
missense			14	4		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	4	0

Variants in RIPK3

This is a list of pathogenic ClinVar variants found in the RIPK3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-24336273-C-T		not specified	Uncertain significance (Oct 10, 2023)
14-24336285-C-T		not specified	Uncertain significance (Jul 26, 2022)
14-24336371-T-C		not specified	Uncertain significance (May 24, 2023)
14-24336905-G-A		not specified	Uncertain significance (Jul 06, 2021)
14-24336920-C-G		not specified	Uncertain significance (Apr 07, 2022)
14-24337096-C-T		not specified	Likely benign (Feb 28, 2023)
14-24337097-G-C		not specified	Uncertain significance (Jan 10, 2022)
14-24337154-T-G		not specified	Likely benign (May 18, 2023)
14-24337210-G-T		not specified	Uncertain significance (Jan 16, 2024)
14-24337246-C-T		not specified	Uncertain significance (Sep 26, 2023)
14-24337264-G-A		not specified	Likely benign (Nov 29, 2021)
14-24337267-C-T		not specified	Likely benign (Oct 05, 2023)
14-24337279-A-G		not specified	Uncertain significance (Nov 09, 2022)
14-24337333-A-G		not specified	Uncertain significance (Jun 30, 2023)
14-24337394-C-T		not specified	Uncertain significance (Oct 10, 2023)
14-24337403-A-G		not specified	Likely benign (Feb 22, 2023)
14-24337408-G-A		not specified	Uncertain significance (Jun 11, 2015)
14-24337878-A-G		not specified	Uncertain significance (Jan 29, 2024)
14-24337945-C-A		not specified	Uncertain significance (Mar 06, 2023)
14-24337989-C-T		not specified	Uncertain significance (Apr 07, 2023)
14-24337992-T-C		not specified	Uncertain significance (Jul 28, 2021)
14-24338007-A-G		not specified	Uncertain significance (Dec 06, 2021)
14-24338028-G-A		not specified	Uncertain significance (Feb 12, 2024)
14-24338272-A-G		not specified	Uncertain significance (Oct 14, 2023)
14-24338429-C-T		not specified	Conflicting classifications of pathogenicity (Jul 13, 2021)

GnomAD

Source: gnomAD

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: 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

	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