HIPK3
protein-codinghomeodomain interacting protein kinase 3
Gene summary
Enables protein serine/threonine kinase activity. Involved in mRNA transcription; negative regulation of apoptotic process; and protein phosphorylation. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~100.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HIPK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005734.5. 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 | 3 | 3 | ||||
| missense | 147 | 4 | 1 | 152 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 153 | 4 | 1 | 158 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005725.3 | 16 | MANE Select | |
| Ensembl | ENSP00000304226.4 | 16 | MANE Select | |
| RefSeq | NP_001041665.1 | 15 | Standard | |
| RefSeq | NP_001265091.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cellular senescence - Homo sapiens (human)
- miR-targeted genes in adipocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- EGFR1
Biological Process
- protein phosphorylation
- apoptotic process
- mRNA transcription
- peptidyl-serine phosphorylation
- peptidyl-threonine phosphorylation
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- ATP binding
Cellular Component
- cytosol
- nuclear body
- PML body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000303296
- Coding exons
- 16
- Length
- 100352
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125747
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.73 | 519 | 642 | 0.808 | 0.0000319 | 7944 |
| Missense (PolyPhen) | 179 | 254.58 | 0.70311 | 3234 | ||
| Synonymous | -0.167 | 238 | 235 | 1.01 | 0.0000119 | 2388 |
| Loss of Function | 5.35 | 13 | 56.3 | 0.231 | 0.00000305 | 672 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF- responsive element (OCFRE). {ECO:0000269|PubMed:14766760, ECO:0000269|PubMed:17210646}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.683
- RVIS EVS
- -0.73
- RVIS percentile EVS
- 14.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.845
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |