TBX19

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

Basic information

Region (hg38): 1:168280876-168314426

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.

• Congenital isolated adrenocorticotropic hormone deficiency (6 variants)
• not provided (3 variants)
• TBX19-related disorder (1 variants)
• Inborn genetic diseases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	12	5	18
missense		3	43	1	1	48
nonsense	3					3
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region			3	1		4
non coding			23	11	16	50
Total	7	5	67	24	22

Highest pathogenic variant AF is 0.000105

Variants in TBX19

This is a list of pathogenic ClinVar variants found in the TBX19 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-168281070-G-A		Congenital isolated adrenocorticotropic hormone deficiency	Benign (Apr 27, 2017)
1-168281088-C-T		TBX19-related disorder	Likely benign (Aug 09, 2019)
1-168281111-C-A			Likely benign (Jan 30, 2023)
1-168281129-T-G		Congenital isolated adrenocorticotropic hormone deficiency	Uncertain significance (Jan 13, 2018)
1-168281152-A-G		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
1-168281161-AGAGT-A		Inborn genetic diseases	Pathogenic (Jul 25, 2014)
1-168281168-G-A			Benign (Dec 25, 2022)
1-168281185-A-C		Inborn genetic diseases	Uncertain significance (May 24, 2023)
1-168281190-G-C		Inborn genetic diseases	Uncertain significance (Dec 16, 2021)
1-168281195-C-T		Congenital isolated adrenocorticotropic hormone deficiency • TBX19-related disorder	Benign (Jan 13, 2024)
1-168281244-CAG-C		Congenital isolated adrenocorticotropic hormone deficiency	Pathogenic (Jun 19, 2018)
1-168281284-A-G		Congenital isolated adrenocorticotropic hormone deficiency	Uncertain significance (Jan 12, 2018)
1-168281313-C-T			Likely benign (Feb 14, 2023)
1-168291157-T-C		Congenital isolated adrenocorticotropic hormone deficiency • not specified • TBX19-related disorder	Conflicting classifications of pathogenicity (Jul 01, 2024)
1-168291162-G-A		Congenital isolated adrenocorticotropic hormone deficiency	Likely pathogenic (Sep 23, 2021)
1-168291166-G-T		Adrenal insufficiency	Uncertain significance (Nov 25, 2011)
1-168291182-A-T		Inborn genetic diseases	Uncertain significance (Aug 12, 2022)
1-168291213-T-G		Congenital isolated adrenocorticotropic hormone deficiency	Pathogenic (Oct 01, 2007)
1-168291217-C-T			Likely benign (Nov 19, 2023)
1-168291218-TC-T		Congenital isolated adrenocorticotropic hormone deficiency	Pathogenic (Oct 22, 2012)
1-168291246-A-G			Uncertain significance (May 04, 2022)
1-168291254-C-T			Uncertain significance (Sep 23, 2021)
1-168291265-C-T			Likely benign (Sep 07, 2022)
1-168291266-G-A		Congenital isolated adrenocorticotropic hormone deficiency	Uncertain significance (Oct 22, 2023)
1-168291271-C-T		Congenital isolated adrenocorticotropic hormone deficiency	Conflicting classifications of pathogenicity (Oct 15, 2023)

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