TBX19

T-box transcription factor 19, the group of T-box transcription factors

Basic information

Region (hg38): 1:168280877-168314426

Links

ENSG00000143178 ∙ NCBI:9095 ∙ OMIM:604614 ∙ HGNC:11596 ∙ Uniprot:O60806 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital isolated adrenocorticotropic hormone deficiency (Definitive), mode of inheritance: AR
• congenital isolated adrenocorticotropic hormone deficiency (Strong), mode of inheritance: AR
• congenital isolated adrenocorticotropic hormone deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adrenocorticotropic hormone deficiency	AR	Endocrine	Individuals may have severe neonatal hypoglycemia, and treatment of adrenocortical insufficiency (eg, with hydrocortisone, fludricortisone) can be effective	Endocrine	4295129; 6314808; 2830787; 8222301; 11290323; 15613420

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBX19 gene.

• not_provided (72 variants)
• Congenital_isolated_adrenocorticotropic_hormone_deficiency (57 variants)
• Inborn_genetic_diseases (56 variants)
• TBX19-related_disorder (5 variants)
• Adrenal_insufficiency (2 variants)
• not_specified (2 variants)
• Pituitary_stalk_interruption_syndrome (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX19 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005149.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	17	6	24
missense	2	4	80	4	1	91
nonsense	5					5
start loss						0
frameshift	3	1				4
splice donor/acceptor (+/-2bp)	2	4	1			7
Total	12	9	82	21	7

Highest pathogenic variant AF is 0.0000991298

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBX19	protein_coding	protein_coding	ENST00000367821	8	33387

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000711	0.912	125635	0	113	125748	0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.564	228	253	0.900	0.0000150	2919
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000716	0.000716
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00185	0.00185
European (Non-Finnish)	0.000432	0.000431
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Corticotropin-releasing hormone signaling pathway (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.278
• rvis_EVS: -0.96
• rvis_percentile_EVS: 9.17

Haploinsufficiency Scores

• pHI: 0.394
• hipred: N
• hipred_score: 0.350
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.614

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tbx19
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland 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); pigmentation phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;anatomical structure morphogenesis;pituitary gland development;regulation of cell population proliferation;cell fate commitment;regulation of cell differentiation;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• 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