SIX2
SIX homeobox 2, the group of SINE class homeoboxes
Basic information
Region (hg38): 2:45005182-45009452
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (58 variants)
- not_specified (35 variants)
- SIX2-related_disorder (9 variants)
- Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIX2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016932.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 25 | 28 | ||||
| missense | 50 | 55 | ||||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 51 | 26 | 6 |
Highest pathogenic variant AF is 0.0000027365472
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SIX2 | protein_coding | protein_coding | ENST00000303077 | 2 | 4270 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.939 | 0.0611 | 125722 | 0 | 9 | 125731 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.519 | 146 | 165 | 0.886 | 0.00000881 | 1875 |
| Missense in Polyphen | 28 | 50.741 | 0.55182 | 603 | ||
| Synonymous | -1.24 | 90 | 76.2 | 1.18 | 0.00000453 | 610 |
| Loss of Function | 2.76 | 0 | 8.86 | 0.00 | 3.96e-7 | 94 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000206 | 0.000206 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000887 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Also acts independently of OSR1 to activate expression of many cap mesenchyme genes, including itself, GDNF and OSR1. During craniofacial development plays a role in growth and elongation of the cranial base through regulation of chondrocyte differentiation. During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1. During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway. Also may be involved in limb tendon and ligament development (By similarity). Plays a role in cell proliferation and migration. {ECO:0000250|UniProtKB:Q62232, ECO:0000269|PubMed:22995329}.;
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- loftool
- 0.0370
- rvis_EVS
- 0.06
- rvis_percentile_EVS
- 58.53
Haploinsufficiency Scores
- pHI
- 0.892
- hipred
- Y
- hipred_score
- 0.837
- ghis
- 0.481
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.166
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Six2
- Phenotype
- cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal phenotype; renal/urinary system phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- six2a
- Affected structure
- pronephric glomerulus
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- kidney development;chondrocyte differentiation;mesenchymal to epithelial transition involved in metanephros morphogenesis;protein import into nucleus;mesodermal cell fate specification;cell population proliferation;anatomical structure morphogenesis;anterior/posterior axis specification;cell migration;regulation of ossification;regulation of chondrocyte differentiation;middle ear morphogenesis;negative regulation of cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic digestive tract morphogenesis;embryonic cranial skeleton morphogenesis;anatomical structure development;nephron development;nephron morphogenesis;mesenchymal stem cell maintenance involved in nephron morphogenesis;condensed mesenchymal cell proliferation;mesenchymal cell differentiation involved in kidney development;regulation of branching involved in ureteric bud morphogenesis;mesenchymal stem cell proliferation;positive regulation of chondrocyte proliferation
- Cellular component
- nucleus;transcription factor complex
- 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;DNA-binding transcription factor activity;transcription factor binding;protein-containing complex binding