SIX4
SIX homeobox 4, the group of SINE class homeoboxes
Basic information
Region (hg38): 14:60709539-60724351
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 SIX4 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 | 0 | |||||
| missense | 52 | 52 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 52 | 0 | 0 |
Variants in SIX4
This is a list of pathogenic ClinVar variants found in the SIX4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-60713421-T-C | not specified | Uncertain significance (May 10, 2024) | ||
| 14-60713528-G-C | not specified | Uncertain significance (Jan 03, 2024) | ||
| 14-60713609-A-G | not specified | Uncertain significance (Jun 16, 2023) | ||
| 14-60713640-G-C | not specified | Uncertain significance (Sep 04, 2024) | ||
| 14-60713666-A-C | not specified | Uncertain significance (Feb 15, 2023) | ||
| 14-60713732-T-C | not specified | Uncertain significance (Sep 08, 2024) | ||
| 14-60713739-C-T | not specified | Uncertain significance (Apr 28, 2023) | ||
| 14-60713798-G-A | not specified | Uncertain significance (Jun 10, 2024) | ||
| 14-60713817-G-T | not specified | Uncertain significance (Aug 30, 2022) | ||
| 14-60713828-G-C | not specified | Uncertain significance (Mar 08, 2025) | ||
| 14-60713864-G-A | not specified | Uncertain significance (Jan 25, 2023) | ||
| 14-60713886-T-C | not specified | Uncertain significance (Oct 06, 2021) | ||
| 14-60713897-T-C | not specified | Uncertain significance (Jul 05, 2024) | ||
| 14-60713901-G-T | not specified | Uncertain significance (Nov 14, 2024) | ||
| 14-60713945-C-T | not specified | Uncertain significance (Jun 29, 2022) | ||
| 14-60713946-C-T | not specified | Uncertain significance (Nov 17, 2022) | ||
| 14-60713954-G-A | not specified | Uncertain significance (Mar 22, 2023) | ||
| 14-60713999-T-C | not specified | Uncertain significance (Jan 30, 2025) | ||
| 14-60714115-G-C | not specified | Uncertain significance (Jul 10, 2024) | ||
| 14-60714172-A-T | not specified | Uncertain significance (Oct 27, 2023) | ||
| 14-60719784-G-A | not specified | Uncertain significance (Aug 30, 2022) | ||
| 14-60719784-G-T | not specified | Uncertain significance (Jul 09, 2021) | ||
| 14-60719795-A-G | not specified | Uncertain significance (Apr 28, 2023) | ||
| 14-60719818-A-T | not specified | Uncertain significance (Jan 31, 2025) | ||
| 14-60719846-T-C | not specified | Uncertain significance (Mar 21, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SIX4 | protein_coding | protein_coding | ENST00000216513 | 3 | 14821 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.695 | 0.305 | 125727 | 0 | 20 | 125747 | 0.0000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.49 | 326 | 411 | 0.793 | 0.0000190 | 5017 |
| Missense in Polyphen | 94 | 133.78 | 0.70266 | 1744 | ||
| Synonymous | 0.565 | 167 | 177 | 0.946 | 0.00000872 | 1658 |
| Loss of Function | 3.48 | 4 | 21.4 | 0.187 | 9.14e-7 | 263 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000705 | 0.0000703 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000294 | 0.000294 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a DNA sequence on these target genes and is involved in processes like cell differentiation, cell migration and cell survival. Transactivates gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present in the Trex site and a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer. Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein. Acts synergistically with SIX1 to regulate target genes involved in formation of various organs, including muscle, kidney, gonad, ganglia, olfactory epithelium and cranial skeleton. Plays a role in several important steps of muscle development. Controls the genesis of hypaxial myogenic progenitors in the dermomyotome by transactivating PAX3 and the delamination and migration of the hypaxial precursors from the ventral lip to the limb buds through the transactivation of PAX3, MET and LBX1. Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6. Controls somitic differentiation in myocyte through MYOG transactivation. Plays a role in synaptogenesis and sarcomere organization by participating in myofiber specialization during embryogenesis by activating fast muscle program in the primary myotome resulting in an up-regulation of fast muscle genes, including ATP2A1, MYL1 and TNNT3. Simultaneously, is also able to activate inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby restricting the activation of the slow muscle genes. During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression. During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression. Plays a role in gonad development by regulating both testis determination and size determination. In gonadal sex determination, transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in SRY up-regulation. In gonadal size determination, transactivates NR5A1 by binding a MEF3 consensus sequence resulting in gonadal precursor cell formation regulation. During olfactory development mediates the specification and patterning of olfactory placode through fibroblast growth factor and BMP4 signaling pathways and also regulates epithelial cell proliferation during placode formation. Promotes survival of sensory neurons during early trigeminal gangliogenesis. In the developing dorsal root ganglia, up- regulates SLC12A2 transcription. Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression. Forms gustatory papillae during development of the tongue. Also plays a role during embryonic cranial skeleton morphogenesis. {ECO:0000250|UniProtKB:Q61321}.;
- Pathway
- Transcriptional misregulation in cancer - Homo sapiens (human);mir-124 predicted interactions with cell cycle and differentiation
(Consensus)
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- loftool
- 0.0835
- rvis_EVS
- 0.31
- rvis_percentile_EVS
- 72.66
Haploinsufficiency Scores
- pHI
- 0.750
- hipred
- Y
- hipred_score
- 0.751
- ghis
- 0.488
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.569
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Six4
- Phenotype
- skeleton phenotype; limbs/digits/tail 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; vision/eye phenotype; normal 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- skeletal muscle tissue development;regulation of synaptic growth at neuromuscular junction;male gonad development;anatomical structure morphogenesis;male sex determination;olfactory placode formation;regulation of protein localization;protein localization to nucleus;inner ear morphogenesis;negative regulation of apoptotic process;negative regulation of neuron apoptotic process;tongue development;sarcomere organization;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;male sex differentiation;thymus development;generation of neurons;embryonic cranial skeleton morphogenesis;anatomical structure development;regulation of epithelial cell proliferation;myoblast migration;pharyngeal system development;myotome development;fungiform papilla morphogenesis;trigeminal ganglion development;metanephric mesenchyme development;regulation of branch elongation involved in ureteric bud branching;positive regulation of ureteric bud formation;positive regulation of branching involved in ureteric bud morphogenesis;skeletal muscle fiber differentiation;negative regulation of satellite cell differentiation
- Cellular component
- nucleus;transcription factor complex;cytoplasm
- Molecular function
- transcription regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific