TBX10

Chr 11

T-box transcription factor 10

Also known as: TBX13, TBX7

NCBI Gene: 347853 ENSG00000167800 UniProt: O75333 OMIM: 604648

This gene encodes a T-box transcription factor that regulates developmental processes through its DNA-binding T-box domain. Mutations cause isolated cleft lip with or without cleft palate. The gene shows minimal constraint against loss-of-function variants (pLI near 0), suggesting the inheritance pattern and pathogenic mechanism may vary depending on the specific variant.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the T-box family of transcription factors. These transcription factors share a DNA-binding domain called the T-box, and play a role in several developmental processes including early embryonic cell fate and organogenesis. The encoded protein is a member of the T-box 1 subfamily. Mutations in this gene are thought to be a cause of isolated cleft lip with or without cleft palate. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.000

Z-score 0.51

OE 0.86 (0.56–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.07Z-score

OE missense 1.01 (0.91–1.13)

224 obs / 221.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.56–1.36)

0≤0.351.4

Missense OE?1.01 (0.91–1.13)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 13 / 15.2Missense obs/exp: 224 / 221.1Syn Z: 0.06

Background carrier burden — how many people carry a rare variant somewhere in TBX10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

531 rare PASS variants

Rare truncating (LoF)

1 in 860

71 rare PASS variants

Rare synonymous (reference)

1 in 210

207 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TBX10. 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 160	1 in 770
South Asian	~43k	1 in 140	1 in 940
Remaining (unassigned)	~30k	1 in 120	1 in 1,000
European (Finnish)	~27k	1 in 390	1 in 3,600
Admixed American	~22k	1 in 120	1 in 730
African / African American	~21k	1 in 71	1 in 1,400
East Asian	~20k	1 in 120	1 in 2,200
Ashkenazi Jewish	~13k	1 in 280	none seen
Middle Eastern	~2,884	1 in 130	≈ 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.

Exome coverage (gnomAD): 8 of 8 coding exons well covered in gnomAD exomes. Genomes: 7 of 8 (exon 1 below).? see exons ↓