FOXI2

Chr 10

forkhead box I2

NCBI Gene: 399823 ENSG00000186766 UniProt: Q6ZQN5 OMIM: 617202

The protein is predicted to function as a DNA-binding transcription factor that regulates gene expression by RNA polymerase II and is involved in anatomical structure development and cell differentiation. Mutations in this gene have not been definitively associated with human disease in pediatric populations. The gene appears to be tolerant to loss-of-function variants based on constraint metrics.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.85

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.000

Z-score -0.17

OE 1.09 (0.55–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.09Z-score

OE missense 1.02 (0.89–1.18)

139 obs / 136.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.09 (0.55–1.85)

0≤0.351.4

Missense OE?1.02 (0.89–1.18)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 5 / 4.6Missense obs/exp: 139 / 136.0Syn Z: -0.88

Background carrier burden — how many people carry a rare variant somewhere in FOXI2?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

579 rare PASS variants

Rare truncating (LoF)

1 in 1,100

74 rare PASS variants

Rare synonymous (reference)

1 in 210

257 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FOXI2. 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 130	1 in 1,100
South Asian	~43k	1 in 100	1 in 750
Remaining (unassigned)	~30k	1 in 98	1 in 2,000
European (Finnish)	~27k	1 in 490	1 in 570
Admixed American	~22k	1 in 110	1 in 960
African / African American	~21k	1 in 110	1 in 1,200
East Asian	~20k	1 in 100	1 in 550
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 2,700
Middle Eastern	~2,884	1 in 92	≈ 1 in 1,800

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓