TBX6

Chr 16ADAR

T-box transcription factor 6

Also known as: SCDO5

NCBI Gene: 6911 ENSG00000149922 UniProt: O95947 OMIM: 602427

TBX6 encodes a T-box transcription factor that regulates axial stem cell fate determination between neural and mesodermal lineages and plays a role in left-right axis patterning during embryonic development. Mutations cause spondylocostal dysostosis 5, a vertebral segmentation disorder affecting the spine and ribs. Inheritance can be either autosomal dominant or autosomal recessive.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spondylocostal dysostosis 5MIM #122600

ADAR

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spondylocostal dysostosis 5; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — TBX6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.007

Z-score 2.57

OE 0.37 (0.21–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.54Z-score

OE missense 0.91 (0.82–1.01)

254 obs / 279.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.21–0.69)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 7 / 19.1Missense obs/exp: 254 / 279.2Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in TBX6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

626 rare PASS variants

Rare truncating (LoF)

1 in 2,000

103 rare PASS variants

Rare synonymous (reference)

1 in 130

272 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TBX6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 2,900
South Asian	~43k	1 in 91	1 in 1,400
Remaining (unassigned)	~30k	1 in 87	1 in 1,600
European (Finnish)	~27k	1 in 140	1 in 830
Admixed American	~22k	1 in 89	1 in 3,700
African / African American	~21k	1 in 75	1 in 3,000
East Asian	~20k	1 in 96	1 in 560
Ashkenazi Jewish	~13k	1 in 670	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 100	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.