TBX15

Chr 1AR

T-box transcription factor 15

Also known as: TBX14

NCBI Gene: 6913 ENSG00000092607 UniProt: Q96SF7 OMIM: 604127

TBX15 encodes a transcriptional regulator that controls mesenchymal precursor cells and chondrocytes during development of the limb skeleton, vertebral column, and head. Biallelic mutations cause Cousin syndrome, an autosomal recessive disorder characterized by skeletal abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.437), consistent with its developmental importance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene belongs to the T-box family of genes, which encode a phylogenetically conserved family of transcription factors that regulate a variety of developmental processes. All these genes contain a common T-box DNA-binding domain. Mutations in this gene are associated with Cousin syndrome.[provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.441 OMIM phenotype

Clinical Summary— TBX15

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.66) — some intolerance to loss-of-function variants.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 109 VUS of 245 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.658

Z-score 3.43

OE 0.19 (0.09–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.99Z-score

OE missense 0.83 (0.74–0.93)

218 obs / 263.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.44)

0≤0.351.4

Missense OE?0.83 (0.74–0.93)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 4 / 20.9Missense obs/exp: 218 / 263.3Syn Z: 1.04

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTBX15-related craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature (Cousin syndrome)LOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5280th %ile

GOF

0.3491th %ile

LOF

0.73top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

245 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic1

VUS109

Likely Benign84

Benign40

Conflicting2

Pathogenic

Likely Pathogenic

109

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	0	0	3
Likely Pathogenic	1	0	0	0	1
VUS	4	98	7	0	109
Likely Benign	0	4	29	51	84
Benign	0	3	34	3	40
Conflicting	—				2
Total	8	105	70	54	239

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap TBX15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →