RIPK4
protein-codingreceptor interacting serine/threonine kinase 4, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes
Gene summary
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]
- ANKRD3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009901
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009901
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0019287
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009901
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RIPK4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020639.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | 52 | 2 | 62 | ||
| missense | 3 | 1 | 148 | 17 | 169 | |
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 6 | 2 | 158 | 70 | 2 | 238 |
Highest pathogenic variant AF is 0.000014868801
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065690.2 | 8 | MANE Select | |
| Ensembl | ENSP00000332454.3 | 8 | MANE Select | |
| Ensembl | ENSP00000330161.2 | 9 | Standard | |
| Ensembl | ENSP00000330161.2 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- morphogenesis of an epithelium
- protein phosphorylation
- positive regulation of NF-kappaB transcription factor activity
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
Cellular Component
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332512
- Coding exons
- 8
- Length
- 27738
- Individuals with no LoFs
- 125491
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 257
- Defined
- 125748
- p
- 0.00102
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.89 | 409 | 532 | 0.769 | 0.0000377 | 5032 |
| Missense (PolyPhen) | 134 | 207.51 | 0.64574 | 2011 | ||
| Synonymous | -1.31 | 278 | 252 | 1.11 | 0.0000196 | 1659 |
| Loss of Function | 3.15 | 9 | 26.5 | 0.340 | 0.00000139 | 282 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000062 | rare |
| Latino/Admixed American | 0.00050 | 0.00049 | rare |
| Ashkenazi Jewish | 0.0033 | 0.0032 | notable |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.0010 | 0.00088 | notable |
| European (Non-Finnish) | 0.0016 | 0.0015 | notable |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.0014 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation. {ECO:0000269|PubMed:12446564, ECO:0000269|PubMed:22197488}.;
- Disease
- DISEASE: 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. {ECO:0000269|PubMed:22197488, ECO:0000269|PubMed:22197489}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.172
Intolerance Scores
- LoFtool
- 0.382
- RVIS EVS
- -1.66
- RVIS percentile EVS
- 2.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.684
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |