TBX19
protein-codingT-box transcription factor 19, the group of T-box transcription factors
Gene summary
This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Mutations in this gene were found in patients with isolated deficiency of pituitary POMC-derived ACTH, suggesting an essential role for this gene in differentiation of the pituitary POMC lineage. ACTH deficiency is characterized by adrenal insufficiency symptoms such as weight loss, lack of appetite (anorexia), weakness, nausea, vomiting, and low blood pressure. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0008720
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0008720
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0008720
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0008720
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: Endocrine
Rationale: Individuals may have severe neonatal hypoglycemia, and treatment of adrenocortical insufficiency (eg, with hydrocortisone, fludricortisone) can be effective
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TBX19 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005149.3. 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 | 1 | 4 | 27 | 6 | 38 | |
| missense | 3 | 5 | 88 | 4 | 1 | 101 |
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 2 | 5 | 3 | 10 | ||
| Total | 14 | 12 | 95 | 31 | 7 | 159 |
Highest pathogenic variant AF is 0.000099129764
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005140.1 | 8 | MANE Select | |
| Ensembl | ENSP00000356795.3 | 8 | MANE Select | |
| Ensembl | ENSP00000397540.1 | 6 | Standard | |
| Ensembl | ENSP00000390731.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Corticotropin-releasing hormone signaling pathway
Biological Process
- regulation of transcription by RNA polymerase II
- anatomical structure morphogenesis
- pituitary gland development
- regulation of cell population proliferation
- cell fate commitment
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- enhancer sequence-specific DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367821
- Coding exons
- 8
- Length
- 33387
- Individuals with no LoFs
- 125635
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 113
- Defined
- 125748
- p
- 0.000449
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.564 | 228 | 253 | 0.900 | 0.0000150 | 2919 |
| Missense (PolyPhen) | 66 | 87.816 | 0.75157 | 1073 | ||
| Synonymous | -0.567 | 112 | 105 | 1.07 | 0.00000731 | 924 |
| Loss of Function | 1.63 | 11 | 18.6 | 0.591 | 9.63e-7 | 213 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00035 | 0.00032 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.0018 | 0.0018 | notable |
| European (Non-Finnish) | 0.00043 | 0.00043 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator involved in developmental processes. Can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters. {ECO:0000269|PubMed:11290323}.;
- Disease
- DISEASE: ACTH deficiency, isolated (IAD) [MIM:201400]: An autosomal recessive disorder that is characterized by adrenal insufficiency symptoms, such as weight loss, lack of appetite (anorexia), weakness, nausea, vomiting and low blood pressure (hypotension). The pituitary hormone ACTH is decreased or absent, and other cortisol and other steroid hormone levels in the blood are abnormally low. {ECO:0000269|PubMed:11290323}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.221
Intolerance Scores
- LoFtool
- 0.278
- RVIS EVS
- -0.96
- RVIS percentile EVS
- 9.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.614
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |