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RIPK4 Gene

protein-coding GIFtS: 58
GCID: GC21M043159

Receptor-Interacting Serine-Threonine Kinase 4

(Previous name: ankyrin repeat domain 3)
(Previous symbol: ANKRD3)

See related diseases
at

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Receptor-Interacting Serine-Threonine Kinase 4¹ ²		PPS2² ⁵
ANKRD3¹ ² ³		Ankyrin Repeat Domain 3¹
PKC-Delta-Interacting Protein Kinase¹ ² ³		ANKK2²
DIK² ³ ⁵		PKK²
Protein Kinase C-Associated Kinase¹ ²		RIP4²
Ankyrin Repeat Domain-Containing Protein 3² ³		Receptor-Interacting Serine/Threonine-Protein Kinase 4²
EC 2.7.11.1³ ⁸		Serine/Threonine-Protein Kinase ANKRD3²
NKRD3² ⁵		EC 2.7.11⁸

External Ids:	HGNC: 496¹	Entrez Gene: 54101²	Ensembl: ENSG00000183421⁷	OMIM: 605706⁵	UniProtKB: P57078³

Export aliases for RIPK4 gene to outside databases

Previous GC identifers: GC00U917001 GC21M042032 GC21M028579

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for RIPK4 Gene:

The protein encoded by this gene is a serine/threonine protein kinase that interacts with protein kinase C-delta.

The encoded protein can also activate NFkappaB and is required for keratinocyte differentiation. This kinase

undergoes autophosphorylation. (provided by RefSeq, Jul 2008)

GeneCards Summary for RIPK4 Gene:

RIPK4 (receptor-interacting serine-threonine kinase 4) is a protein-coding gene. Diseases associated with RIPK4 include tetanus neonatorum, and severe nonproliferative diabetic retinopathy. GO annotations related to this gene include protein serine/threonine kinase activity. An important paralog of this gene is RIPK3.

UniProtKB/Swiss-Prot: RIPK4_HUMAN, P57078

Function: Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a

role in NF-kappa-B activation

Gene Wiki entry for RIPK4 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000021.9 NC_018932.2 NT_011512.12

Regulatory elements:

Regulatory transcription factor binding sites in the RIPK4 gene promoter:
Max1 RP58 AML1a Lmo2 Nkx2-5 AP-2gamma CREB CP2 deltaCREB c-Myc
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: RIPK4 promoter sequence

Search Chromatin IP Primers for RIPK4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RIPK4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 21q22.3 Ensembl cytogenetic band: 21q22.3 HGNC cytogenetic band: 21q22.3

RIPK4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RIPK4 gene location

GeneLoc information about chromosome 21 GeneLoc Exon Structure

GeneLoc location for GC21M043159: view genomic region (about GC identifiers)

Start:	43,159,529 bp from pter	End:	43,187,266 bp from pter
Size:	27,738 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: RIPK4_HUMAN, P57078 (See protein sequence)

Recommended Name: Receptor-interacting serine/threonine-protein kinase 4

Size: 832 amino acids; 91611 Da

Subunit: Interacts with PRKCB (By similarity). Interacts with TRAF1, TRAF2, TRAF3 and TRAF5. Interacts with

BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4

Secondary accessions: Q96KH0

Alternative splicing: 2 isoforms: P57078-1 P57078-2

Explore the universe of human proteins at neXtProt for RIPK4: NX_P57078

Explore proteomics data for RIPK4 at MOPED

Post-translational modifications:

May be phosphorylated by MAP3K2 and MAP3K3 (By similarity)¹

Proteolytically cleaved by during Fas-induced apoptosis. Cleavage at Asp-388 and Asp-426¹

Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation

of NF-kappa-B¹

Ubiquitination² at Lys51, Lys145

Modification sites at PhosphoSitePlus

2 DME Specific Peptides for RIPK4 (P57078)

LHLDLKP

HLDLKPAN

See RIPK4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_065690.2

ENSEMBL proteins:

ENSP00000332454 ENSP00000330161 ENSP00000441754 ENSP00000442901

RIPK4 Human Recombinant Protein Products:

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

ANKRD: Ankyrin repeat domain containing

IUPHAR Guide to PHARMACOLOGY protein family classification: receptor-interacting serine-threonine kinase 4

Receptor interacting protein kinase (RIPK) family

Selected InterPro protein domains (see all 6):

IPR017441 Protein_kinase_ATP_BS

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_dom

IPR002110 Ankyrin_rpt

Graphical View of Domain Structure for InterPro Entry P57078

ProtoNet protein and cluster: P57078

1 Blocks protein domain: IPB002110 Ankyrin repeat signature

UniProtKB/Swiss-Prot: RIPK4_HUMAN, P57078

Similarity: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family

Similarity: Contains 10 ANK repeats

Similarity: Contains 1 protein kinase domain

RIPK4 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: RIPK4_HUMAN, P57078

Function: Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a

role in NF-kappa-B activation

Catalytic activity: ATP + a protein = ADP + a phosphoprotein

Enzyme Numbers (IUBMB): EC 2.7.11.1¹ ² EC 2.7.11²

Gene Ontology (GO): Selected molecular function terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004672	protein kinase activity	--	--
GO:0004674	protein serine/threonine kinase activity	IEA	--
GO:0004713	protein tyrosine kinase activity	--	--
GO:0005515	protein binding	IPI	--
GO:0005524	ATP binding	IEA	--

RIPK4 for ontologies About GeneDecksing

Phenotypes:
4 GenomeRNAi human phenotypes for RIPK4:

Decreased substrate adherent c

Downregulation of NF-kappaB pa

Increased colony dispersion (i

10 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Ripk4):

cellular	craniofacial	digestive/alimentary	hematopoietic system	homeostasis/metabolism
immune system	integument	limbs/digits/tail	mortality/aging	respiratory system

RIPK4 for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-out Ripk4^tm1Pmh for RIPK4

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for RIPK4

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for RIPK4

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genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for RIPK4

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		Block miRNA regulation of human, mouse, rat RIPK4 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate RIPK4 (see all 9):
		hsa-miR-103b hsa-miR-130a* hsa-miR-575 hsa-miR-23c hsa-miR-23b hsa-miR-889 hsa-miR-489 hsa-miR-23a

		SwitchGear 3'UTR luciferase reporter plasmid: RIPK4 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for RIPK4
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Gene Editing
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DNA2.0 Custom Protein Engineering Service for RIPK4

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		DNA2.0 Custom Codon Optimized Gene Synthesis Service for RIPK4
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RIPK4

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

RIPK4_HUMAN, P57078: Cytoplasm. Membrane; Peripheral membrane protein (By similarity)

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
cytosol	3
nucleus	3
cytoskeleton	2
extracellular	2
plasma membrane	2
endoplasmic reticulum	1
mitochondrion	1

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Gene Ontology (GO): 3 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	--
GO:0005737	cytoplasm	ISS	--
GO:0016020	membrane	IEA	--

RIPK4 for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for RIPK4 About

See pathways by source

SuperPath

Contained pathways About

Wnt / Hedgehog / Notch

Wnt / Hedgehog / Notch

NF-kappaB Signaling

NF-kappaB Signaling

Pathways by source See SuperPaths
Show all pathways

2 Cell Signaling Technology (CST) Pathways for RIPK4

	Wnt / Hedgehog / Notch
	NF-kappaB Signaling

RIPK4 for pathways About GeneDecksing

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for RIPK4
Interactions:

GeneGlobe Interaction Network for RIPK4

STRING Interaction Network Preview (showing 5 interactants - click image to see 10)

Selected Interacting proteins for RIPK4 (P57078^{1, 3} ENSP00000332454⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 15)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
BIRC2	Q13490¹, ENSP00000227758⁴	EBI-4422308,EBI-514538 STRING: ENSP00000227758
XIAP	P98170¹, ENSP00000347858⁴	EBI-4422308,EBI-517127 STRING: ENSP00000347858
BIRC3	Q13489¹, ENSP00000263464⁴	EBI-4422308,EBI-517709 STRING: ENSP00000263464
TRAF1	Q13077³	I2D: score=1
TRAF2	Q12933³	I2D: score=1

About this table

Gene Ontology (GO): 3 biological process terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002009	morphogenesis of an epithelium	IMP	--
GO:0006468	protein phosphorylation	--	--
GO:0051092	positive regulation of NF-kappaB transcription factor activity	IMP	--

RIPK4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for RIPK4

3 Novoseek inferred chemical compound relationships for RIPK4 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
kininogen	63.6	2	8856132 (1)
heparin	16.1	2	7569739 (1), 8933290 (1)
serine	11.8	4	12091384 (1), 16256200 (1)

RIPK4 for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for RIPK4 gene:

NM_020639.2

Unigene Cluster for RIPK4:

Receptor-interacting serine-threonine kinase 4

Hs.517310 [show with all ESTs]

Unigene Representative Sequence: NM_020639

4 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000332512(uc002yzn.1) ENST00000352483 ENST00000544709 ENST00000542057

miRNA Products:		Block miRNA regulation of human, mouse, rat RIPK4 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate RIPK4 (see all 9):
		hsa-miR-103b hsa-miR-130a* hsa-miR-575 hsa-miR-23c hsa-miR-23b hsa-miR-889 hsa-miR-489 hsa-miR-23a

		SwitchGear 3'UTR luciferase reporter plasmid: RIPK4 3' UTR sequence

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		QuantiFast Probe-based Assays in human, mouse, rat RIPK4

Additional mRNA sequence:

AB047783.1 AF308292.1 AJ278016.1 AK027424.1 AK296685.1 AK302592.1 AK316412.1 AL137448.1

BC035755.1 BC110617.1 BC110618.1

4 DOTS entries:

DT.109841 DT.95265905 DT.91723205 DT.95265906

Selected AceView cDNA sequences (see all 66):

BM980861 AI061211 NM_020639 AA932836 AI308062 BC035755 BE350899 W72972

BM850058 AI279596 CB116630 AI620860 BM675971 BM782022 BM924233 AW189426

CD630274 AB047783 W37838 BE326278 BI868794 BI868710 BM823971 AW129556

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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RIPK4 expression in normal human tissues (normalized intensities) RIPK4 embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: --

About this image

RIPK4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 11) fully expand


Kidney (Urinary System) fully expand to see all 6 entries
Ureteric Bud Cells Ureteric Bud
Metanephros

Blood (Cardiovascular System) fully expand to see all 3 entries
Hematopoietic Stem Cells Hematopoietic Bone Marrow

Primitive Streak (Early Embryonic Tissues) fully expand to see all 2 entries
Notochord Cells Notochord
Notochord

Thymus (Hematopoietic System)
Double Positive Thymocytes Thymus

Gut Tube (Gastrointestinal Tract)
Foregut

RIPK4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

RIPK4 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.517310

Custom PCR Arrays for RIPK4

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RIPK4

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for RIPK4 gene from Selected species (see all 13) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Ripk4^{1 , 5}	receptor-interacting serine-threonine kinase 4^{1, 5}	84.91(n)¹ 90.69(a)¹		16 (57.63 cM)⁵ 72388¹ NM_023663.6¹ NP_076152.2¹ 97741933⁵
chicken (Gallus gallus)	Aves	RIPK4¹	receptor-interacting serine-threonine kinase 4	72.61(n) 77.52(a)		418529 XM_416738.3 XP_416738.3
lizard (Anolis carolinensis)	Reptilia	RIPK4⁶	receptor-interacting serine-threonine kinase 4	75(a)	1 ↔ 1	3(138237713-138270799)
African clawed frog (Xenopus laevis)	Amphibia	ankrd3-prov²	ankyrin repeat domain 3	75.26(n)		BC043634.1
zebrafish (Danio rerio)	Actinopterygii	Dr.18839²	Danio rerio protein kinase PKK (pkk) mRNA, complete more	73.96(n)		BC045432.1

ENSEMBL Gene Tree for RIPK4 (if available)
TreeFam Gene Tree for RIPK4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for RIPK4 gene

RIPK3² RIPK1² RIPK2² ANKK1²

14 SIMAP similar genes for RIPK4 using alignment to 3 protein entries: RIPK4_HUMAN (see all proteins):

DKFZp434B2328 dik ANKDD1A PSMD10 DKFZp761E1322 MTPN

PPP1R12B NRARP tec ANKRD29 GABPB1 ANKK1

CDKN2C IkBa

RIPK4 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 21 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_067331⁴		Popliteal pterygium syndrome, lethal type (PPS-L)⁴	--	see VAR_067331	2	I N	mis⁴		0	--	--	--	--
VAR_067333⁴		Popliteal pterygium syndrome, lethal type (PPS-L)⁴	--	see VAR_067333	2	T I	mis⁴		0	--	--	--	--
VAR_067332⁴		Popliteal pterygium syndrome, lethal type (PPS-L)⁴	--	see VAR_067332	2	I N	mis⁴		0	--	--	--	--
rs368435939^1,2	C	--	28602866(+)	`TATCA-/ATTTTTTA`	1	--	cds¹		0	--	--	--	--
rs12482045^1,2	C,F,H	--	33659997(+)	`TCTTGT/CTTTTA`	1	--	ds500¹		20		NS EA NA	2360
rs187200224^1,2		--	33660016(+)	`ACAGGA/CAAGTA`	1	--	ds500¹		0	--	--	--	--
rs79110933^1,2	C	--	33660060(+)	`ACTCTC/TGAACA`	1	--	ds500¹		0	--	--	--	--
rs146850248^1,2	C	--	33660064(+)	`CGAAC-/AGGT AGGTA`	1	--	ds500¹		0	--	--	--	--
rs147676011^1,2		--	33660149(+)	`CTATGG/TACTAC`	1	--	ds500¹		0	--	--	--	--
rs181596121^1,2		--	33660163(+)	`TGTCAC/GTTTTC`	1	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for RIPK4 (43159529 - 43187266 bp)

Structural Variations
Database of Genomic Variants (DGV) 4 variations for RIPK4: About this table

Variant ID	Type	Subtype	PubMed ID
nsv459265	CNV	Loss	19166990
nsv913760	CNV	Loss	21882294
nsv913766	CNV	Gain	21882294
dgv4743n71	CNV	Gain	21882294

Human Gene Mutation Database (HGMD): RIPK4

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing RIPK4

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 605706
OMIM disorders: 263650
UniProtKB/Swiss-Prot: RIPK4_HUMAN, P57078

Popliteal pterygium syndrome, lethal type (PPS-L) [MIM:263650]: An autosomal recessive disorder

characterized by multiple popliteal pterygia leading to severe arthrogryposis, ankyloblepharon filiforme adnatum,

filiform bands between the jaws, synostosis of the carpal/tarsal and phalangeal bones in the hands and feet,

digital hypoplasia/aplasia, complete soft-tissue syndactyly, lack of nails, lack of scalp hair, eyebrows and

eyelashes, blepharophimosis, cleft lip and/or palate, and hypoplastic external genitalia. Early lethality is

common, although survival into childhood and beyond has been reported. Note=The disease is caused by mutations

affecting the gene represented in this entry

Selected diseases for RIPK4 (see all 26): About MalaCards

tetanus neonatorum severe nonproliferative diabetic retinopathy popliteal pterygium syndrome 2, lethal type popliteal pterygium syndrome lethal type

mesenteric lymphadenitis clear cell adenoma lymphadenitis popliteal pterygium syndrome

tetanus pterygium blepharophimosis synostosis

syndactyly gout diffuse large b-cell lymphoma b-cell lymphomas

acute pancreatitis cleft lip graves' disease diabetic retinopathy

1 disease from the University of Copenhagen DISEASES database for RIPK4:

Severe nonproliferative diabetic retinopathy

RIPK4 for disorders About GeneDecksing

2 Novoseek inferred disease relationships for RIPK4 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
necrosis	23.6	5	12091384 (1), 17039240 (1), 18025152 (1)
tumors	0	6	18025152 (2), 12091384 (1), 17039240 (1)

Genetic Association Database (GAD): RIPK4
Human Genome Epidemiology (HuGE) Navigator: RIPK4 (1 document)

Export disorders for RIPK4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for RIPK4 gene, integrated from 10 sources (see all 34):
(articles sorted by number of sources associating them with RIPK4)

Utopia: connect your pdf to the dynamic
world of online information

The DNA sequence of human chromosome 21. (PubMed id 10830953)^{1, 2, 3} Hattori M.... Yaspo M.-L. (Nature 2000)
RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF-kappa B and is processed during apoptosis. (PubMed id 12446564)^{1, 2, 9} Meylan E.... Tschopp J. (EMBO Rep. 2002)
Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus. (PubMed id 22197488)^{1, 2} Mitchell K.... Dixon M.J. (Am. J. Hum. Genet. 2012)
cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4). (PubMed id 21931591)^{1, 2} Bertrand M.J.... Vandenabeele P. (PLoS ONE 2011)
Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)^{1, 4} Rose J.E....Uhl G.R. (Mol. Med. 2010)
Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase. (PubMed id 11278382)^{1, 9} Chen L....Pillai S. (J. Biol. Chem. 2001)
Protein kinase C-associated kinase can activate NFkappaB in both a kinase-dependent and a kinase-independent manner. (PubMed id 12676934)^{1, 9} Moran S.T....Pillai S. (J. Biol. Chem. 2003)
Regulation of NF-kappaB activity and keratinocyte differentiation by the RIP4 protein: implications for cutaneous wound repair. (PubMed id 17039240)^{1, 9} Adams S....Munz B. (J. Invest. Dermatol. 2007)
Protein kinase C-associated kinase is required for NF-kappaB signaling and survival in diffuse large B-cell lymphoma cells. (PubMed id 18025152)^{1, 9} Kim S.W....Zhao J. (Blood 2008)
Phosphorylation of Dishevelled by protein kinase RIPK4 regulates Wnt signaling. (PubMed id 23371553)¹ Huang X....Dixit V.M. (Science 2013)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 54101	HGNC: 496	AceView: RIPK4	Ensembl:ENSG00000183421	euGenes: HUgn54101
ECgene: RIPK4	H-InvDB: RIPK4

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for RIPK4	Pharmacogenomics, SNPs, Pathways

Intellectual Property for RIPK4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for RIPK4 gene:
Search GeneIP for patents involving RIPK4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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Receptor-Interacting Serine-Threonine Kinase 4

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Receptor-Interacting Serine-Threonine Kinase 4

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