TGIF1
TGFB induced factor homeobox 1, the group of TALE class homeoboxes and pseudogenes
Basic information
Region (hg38): 18:3411608-3459978
Previous symbols: [ "HPE4", "TGIF" ]
Links
Phenotypes
GenCC
Source:
- holoprosencephaly 4 (Strong), mode of inheritance: AD
- holoprosencephaly 4 (Strong), mode of inheritance: AD
- holoprosencephaly 4 (Definitive), mode of inheritance: AD
- holoprosencephaly 4 (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Holoprosencephaly 4 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Endocrine; Neurologic | 10835638; 16199538; 20104608; 22125506; 21940735 |
| Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus |
ClinVar
This is a list of variants' phenotypes submitted to
- Holoprosencephaly_4 (75 variants)
- not_provided (50 variants)
- Inborn_genetic_diseases (19 variants)
- TGIF1-related_disorder (14 variants)
- not_specified (11 variants)
- Holoprosencephaly_sequence (3 variants)
- Disorder_of_sexual_differentiation (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGIF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003244.4. 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 | 22 | 26 | ||||
| missense | 57 | 67 | ||||
| nonsense | 3 | |||||
| start loss | 0 | |||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 4 | 6 | 58 | 25 | 7 |
Highest pathogenic variant AF is 0.000123286
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TGIF1 | protein_coding | protein_coding | ENST00000330513 | 3 | 46804 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0105 | 0.950 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.178 | 225 | 233 | 0.967 | 0.0000128 | 2550 |
| Missense in Polyphen | 30 | 66.247 | 0.45285 | 793 | ||
| Synonymous | -0.651 | 107 | 98.8 | 1.08 | 0.00000540 | 904 |
| Loss of Function | 1.78 | 5 | 11.5 | 0.433 | 5.14e-7 | 127 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII- RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities.;
- Disease
- DISEASE: Holoprosencephaly 4 (HPE4) [MIM:142946]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. {ECO:0000269|PubMed:10835638, ECO:0000269|PubMed:15221788}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- TGF-beta signaling pathway - Homo sapiens (human);TGF-Ncore;Androgen receptor signaling pathway;TGF-beta Signaling Pathway;Tgif disruption of Shh signaling;TGF-beta Receptor Signaling;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Downregulation of SMAD2/3:SMAD4 transcriptional activity;AndrogenReceptor;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;EGFR1;Coregulation of Androgen receptor activity;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Regulation of nuclear SMAD2/3 signaling
(Consensus)
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- loftool
- 0.310
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 57.41
Haploinsufficiency Scores
- pHI
- 0.107
- hipred
- Y
- hipred_score
- 0.597
- ghis
- 0.562
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tgif1
- Phenotype
- skeleton phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear 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); limbs/digits/tail 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); normal phenotype; reproductive system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; taste/olfaction phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- tgif1
- Affected structure
- Muller cell
- Phenotype tag
- abnormal
- Phenotype quality
- molecular quality
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;multicellular organism development;response to drug;cellular response to growth factor stimulus
- Cellular component
- nucleoplasm
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;co-SMAD binding