TBX19

Chr 1AR

T-box transcription factor 19

Also known as: TBS19, TPIT, dJ747L4.1

NCBI Gene: 9095ENSG00000143178UniProt: O60806

TBX19 encodes a T-box transcription factor that activates POMC gene expression and is essential for differentiation of the pituitary POMC lineage. Biallelic mutations cause isolated adrenocorticotropic hormone (ACTH) deficiency, leading to adrenal insufficiency with symptoms including weight loss, anorexia, weakness, nausea, vomiting, and hypotension. The condition follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Adrenocorticotropic hormone deficiencyMIM #201400
AR
UniProtACTH deficiency, isolated
0
Active trials
16
Pubs (1 yr)
64
P/LP submissions
16%
P/LP missense
0.98
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— TBX19
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 113 VUS of 251 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — TBX19
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.63
OE 0.59 (0.37–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.56Z-score
OE missense 0.90 (0.81–1.00)
228 obs / 253.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.37–0.98)
0≤0.351.4
Missense OE0.90 (0.81–1.00)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 11 / 18.6Missense obs/exp: 228 / 253.2Syn Z: -0.57
DN
0.6840th %ile
GOF
0.5071th %ile
LOF
0.50top 25%

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
LOF28% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

251 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic11
VUS113
Likely Benign45
Benign31
Conflicting7
32
Pathogenic
11
Likely Pathogenic
113
VUS
45
Likely Benign
31
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
3
23
0
32
Likely Pathogenic
6
4
1
0
11
VUS
1
86
24
2
113
Likely Benign
0
3
17
25
45
Benign
0
1
24
6
31
Conflicting
—7
Total13978933239

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TBX19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients