RIPK4
Chr 21ARreceptor interacting serine/threonine kinase 4
Also known as: ANKK2, ANKRD3, CHANDS, DIK, NKRD3, PKK, PPS2, RIP4
RIPK4 encodes a serine/threonine protein kinase that phosphorylates plakophilin-1 to promote keratinocyte differentiation and cell adhesion, playing an essential role in embryonic skin development and adult skin homeostasis. Autosomal recessive mutations cause CHAND syndrome and Bartsocas-Papas type 1 popliteal pterygium syndrome, both severe developmental disorders affecting skin, limbs, and other organ systems. The gene is highly intolerant to loss-of-function variants (LOEUF 0.594), reflecting its critical developmental role.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
412 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 3 | 77 | 0 | 81 |
Likely Pathogenic | 1 | 1 | 2 | 0 | 4 |
VUS | 0 | 138 | 43 | 8 | 189 |
Likely Benign | 0 | 14 | 24 | 42 | 80 |
Benign | 0 | 2 | 27 | 12 | 41 |
Conflicting | — | 10 | |||
| Total | 2 | 158 | 173 | 62 | 405 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RIPK4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools