TBX15

Chr 1AR

T-box transcription factor 15

Also known as: TBX14

NCBI Gene: 6913ENSG00000092607UniProt: Q96SF7

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]

Primary Disease Associations & Inheritance

Cousin syndromeMIM #260660
AR
262
ClinVar variants
14
Pathogenic / LP
0.66
pLI score
0
Active trials
Clinical Summary— TBX15
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.66) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 115 VUS of 262 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.99Z-score
OE missense 0.83 (0.74–0.93)
218 obs / 263.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.09–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.74–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 4 / 20.9Missense obs/exp: 218 / 263.3Syn Z: 1.04

ClinVar Variant Classifications

262 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS115
Likely Benign85
Benign40
Conflicting2
13
Pathogenic
1
Likely Pathogenic
115
VUS
85
Likely Benign
40
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
11
0
13
Likely Pathogenic
1
0
0
0
1
VUS
1
97
17
0
115
Likely Benign
0
4
30
51
85
Benign
0
3
34
3
40
Conflicting
—2
Total41049254256

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

View in ClinVar →

Protein Context — Lollipop Plot

TBX15 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TBX15-related craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature (Cousin syndrome)

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cousin syndrome

MIM #260660

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The overexpression and clinical significance of TBX15 in human gliomas.
Yan D et al.·Sci Rep
2023
An abdominal obesity missense variant in the adipocyte thermogenesis gene TBX15 is implicated in adaptation to cold in Finns.
Deal M et al.·Am J Hum Genet
2024
Mutations in the TBX15-ADAMTS2 pathway associate with a novel soft palate dysplasia.
Zhang Y et al.·Hum Mutat
2022
miR-4732-3p prevents lung cancer progression via inhibition of the TBX15/TNFSF11 axis.
Li P et al.·Epigenomics
2023
Expanding the Clinical Spectrum of Cousin Syndrome: A Novel Biallelic Missense Variant in TBX15 Causing a Milder Phenotype.
Detiger SEL et al.·Am J Med Genet A
2025Case report
Ovarian cancer detection by DNA methylation in cervical scrapings.
Wu TI et al.·Clin Epigenetics
2019
TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome.
Lausch E et al.·Am J Hum Genet
2008Case report
Functional Pathway and Process Enrichment Analysis of Genes Associated With Morphological Abnormalities of the Outer Ear.
Meng X et al.·J Craniofac Surg
2023Review
CircPVT1 promotes progression in clear cell renal cell carcinoma by sponging miR-145-5p and regulating TBX15 expression.
Zheng Z et al.·Cancer Sci
2021
MiR-212-5p inhibits the malignant behavior of clear cell renal cell carcinoma cells by targeting TBX15.
Deng JH et al.·Eur Rev Med Pharmacol Sci
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools