GTF2IRD1
protein-codingGTF2I repeat domain containing 1
Gene summary
The protein encoded by this gene contains five GTF2I-like repeats and each repeat possesses a potential helix-loop-helix (HLH) motif. It may have the ability to interact with other HLH-proteins and function as a transcription factor or as a positive transcriptional regulator under the control of Retinoblastoma protein. This gene plays a role in craniofacial and cognitive development and mutations have been associated with Williams-Beuren syndrome, a multisystem developmental disorder caused by deletion of multiple genes at 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]
- WBSCR11
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~148.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GTF2IRD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005685.4. 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 | 2 | 48 | 6 | 56 | ||
| missense | 1 | 124 | 8 | 133 | ||
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 1 | 139 | 56 | 6 | 202 |
Highest pathogenic variant AF is 0.0000034267464
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005676.3 | 26 | MANE Select | |
| Ensembl | ENSP00000408477.2 | 26 | MANE Select | |
| RefSeq | NP_001186136.1 | 26 | Standard | |
| RefSeq | NP_001397817.1 | 25 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Basal transcription factors - Homo sapiens (human)
- cGMP-PKG signaling pathway - Homo sapiens (human)
- Herpes simplex infection - Homo sapiens (human)
Biological Process
- regulation of transcription, DNA-templated
- regulation of transcription by RNA polymerase II
- transcription by RNA polymerase II
- multicellular organism development
- transition between slow and fast fiber
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- DNA-binding transcription factor activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000455841
- Coding exons
- 26
- Length
- 148812
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125747
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.66 | 444 | 632 | 0.702 | 0.0000421 | 6309 |
| Missense (PolyPhen) | 114 | 200.23 | 0.56934 | 2020 | ||
| Synonymous | 0.327 | 269 | 276 | 0.975 | 0.0000201 | 2004 |
| Loss of Function | 5.36 | 10 | 51.5 | 0.194 | 0.00000282 | 578 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation. May repress GTF2I transcriptional functions, by preventing its nuclear residency, or by inhibiting its transcriptional activation. May contribute to slow-twitch fiber type specificity during myogenesis and in regenerating muscles. Binds troponin I slow-muscle fiber enhancer (USE B1). Binds specifically and with high affinity to the EFG sequences derived from the early enhancer of HOXC8 (By similarity). {ECO:0000250, ECO:0000269|PubMed:11438732}.;
- Disease
- DISEASE: Note=GTF2IRD1 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of GTF2IRD1 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.;
Recessive Scores
- pRec
- 0.160
Intolerance Scores
- LoFtool
- 0.305
- RVIS EVS
- -1.39
- RVIS percentile EVS
- 4.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.733
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |