HIPK2
homeodomain interacting protein kinase 2
Basic information
Region (hg38): 7:139561570-139777998
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIPK2 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 | 3 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 3 | 0 |
Variants in HIPK2
This is a list of pathogenic ClinVar variants found in the HIPK2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-139575149-C-T | Likely benign (Sep 01, 2022) | |||
| 7-139604132-G-A | not specified | Uncertain significance (Dec 01, 2022) | ||
| 7-139614394-C-T | not specified | Uncertain significance (May 30, 2023) | ||
| 7-139626627-G-A | not specified | Likely benign (Oct 08, 2024) | ||
| 7-139626689-C-T | not specified | Uncertain significance (May 20, 2024) | ||
| 7-139626708-C-A | not specified | Uncertain significance (Jan 02, 2024) | ||
| 7-139628984-T-G | not specified | Uncertain significance (Mar 30, 2024) | ||
| 7-139716068-C-G | not specified | Uncertain significance (Dec 17, 2023) | ||
| 7-139716104-C-T | not specified | Uncertain significance (Dec 27, 2022) | ||
| 7-139716265-T-C | not specified | Uncertain significance (Mar 08, 2024) | ||
| 7-139716550-G-A | not specified | Uncertain significance (Mar 19, 2024) | ||
| 7-139716564-A-G | Likely benign (May 01, 2022) | |||
| 7-139716710-C-T | not specified | Uncertain significance (Oct 13, 2023) | ||
| 7-139716784-A-G | not specified | Uncertain significance (Jan 22, 2024) | ||
| 7-139716804-G-C | not specified | Uncertain significance (Feb 15, 2023) | ||
| 7-139716959-A-T | not specified | Uncertain significance (Nov 21, 2023) | ||
| 7-139716979-G-A | not specified | Uncertain significance (May 29, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HIPK2 | protein_coding | protein_coding | ENST00000406875 | 15 | 231262 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000212 | 124987 | 0 | 8 | 124995 | 0.0000320 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.86 | 509 | 726 | 0.701 | 0.0000448 | 7780 |
| Missense in Polyphen | 127 | 231.31 | 0.54905 | 2632 | ||
| Synonymous | 0.822 | 294 | 313 | 0.941 | 0.0000225 | 2419 |
| Loss of Function | 6.14 | 3 | 49.7 | 0.0603 | 0.00000262 | 550 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000156 | 0.000155 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000447 | 0.0000442 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO- protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53- dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation- mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850}.;
- Pathway
- Cellular senescence - Homo sapiens (human);TGF-Ncore;miR-222 in Exercise-Induced Cardiac Growth;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;RNA Polymerase II Transcription;EGFR1;Regulation of TP53 Activity through Phosphorylation;C-MYB transcription factor network;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Transcriptional regulation by RUNX1;p53 pathway
(Consensus)
Recessive Scores
- pRec
- 0.233
Haploinsufficiency Scores
- pHI
- 0.508
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.589
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hipk2
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype;
Zebrafish Information Network
- Gene name
- hipk2
- Affected structure
- melanocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;eye development;protein phosphorylation;DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator;transforming growth factor beta receptor signaling pathway;smoothened signaling pathway;adult walking behavior;positive regulation of cell population proliferation;anterior/posterior pattern specification;retina layer formation;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;modulation by virus of host morphology or physiology;neuron differentiation;erythrocyte differentiation;positive regulation of transforming growth factor beta receptor signaling pathway;negative regulation of BMP signaling pathway;PML body organization;positive regulation of protein binding;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;positive regulation of DNA binding;negative regulation of neuron apoptotic process;positive regulation of angiogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of JNK cascade;embryonic camera-type eye morphogenesis;voluntary musculoskeletal movement;positive regulation of DNA-binding transcription factor activity;regulation of cell cycle;embryonic retina morphogenesis in camera-type eye;lens induction in camera-type eye;SMAD protein signal transduction;iris morphogenesis;cellular response to hypoxia;intrinsic apoptotic signaling pathway;regulation of signal transduction by p53 class mediator;negative regulation of ubiquitin-dependent protein catabolic process
- Cellular component
- nucleus;nucleoplasm;cytoplasm;nuclear body;PML body;RNA polymerase II transcription factor complex
- Molecular function
- RNA polymerase II activating transcription factor binding;transcription coactivator activity;transcription corepressor activity;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;SMAD binding;virion binding