FOXB1

Chr 15

forkhead box B1

Also known as: FKH5, HFKH-5

NCBI Gene: 27023 ENSG00000171956 UniProt: Q99853

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including mammary gland development; nervous system development; and visual learning. Predicted to be located in chromatin and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.39LOEUF

pLI 0.906

Z-score 2.56

OE 0.00 (0.00–0.39)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.48Z-score

OE missense 0.70 (0.61–0.81)

138 obs / 196.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.39)

0≤0.351.4

Missense OE?0.70 (0.61–0.81)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 0 / 7.6Missense obs/exp: 138 / 196.5Syn Z: -0.04

Background carrier burden — how many people carry a rare variant somewhere in FOXB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

463 rare PASS variants

Rare truncating (LoF)

1 in 23,000

21 rare PASS variants

Rare synonymous (reference)

1 in 210

228 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FOXB1. 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 490	1 in 28,000
South Asian	~43k	1 in 160	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 170	none seen
European (Finnish)	~27k	1 in 960	≈ 1 in 8,400
Admixed American	~22k	1 in 270	≈ 1 in 22,000
African / African American	~21k	1 in 150	none seen
East Asian	~20k	1 in 170	≈ 1 in 9,700
Ashkenazi Jewish	~13k	1 in 810	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

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): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓