RIPK2

receptor interacting serine/threonine kinase 2, the group of Caspase recruitment domain containing

Basic information

Region (hg38): 8:89757805-89791064

Links

ENSG00000104312 ∙ NCBI:8767 ∙ OMIM:603455 ∙ HGNC:10020 ∙ Uniprot:O43353 ∙ 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 RIPK2 gene.

• Inborn genetic diseases (12 variants)
• not provided (4 variants)
• not specified (1 variants)

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				1	1	2
missense			12	1	1	14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	12	2	3

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)
8-89765483-A-G		not specified	Uncertain significance (Nov 18, 2023)
8-89766285-G-A		Leprosy, susceptibility to, 1	Uncertain risk allele (Jun 10, 2022)
8-89769800-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)
8-89772762-G-A		not specified	Uncertain significance (Apr 22, 2022)
8-89772765-C-T		not specified	Uncertain significance (Jul 13, 2022)
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)
8-89780156-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)
8-89789344-A-G		not specified	Uncertain significance (Nov 17, 2022)
8-89789416-T-C		not specified	Uncertain significance (Oct 06, 2021)
8-89789467-A-G		not specified	Likely benign (Nov 07, 2022)
8-89790118-G-A		not specified	Uncertain significance (Nov 10, 2022)
8-89790169-C-T		not specified	Uncertain significance (Sep 12, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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