FOXJ2

Chr 12

forkhead box J2

Also known as: FHX

NCBI Gene: 55810 ENSG00000065970 UniProt: Q9P0K8 OMIM: 619162

FOXJ2 encodes a transcriptional activator that binds specific DNA sequences to regulate gene expression and plays an important role in spermatogenesis, particularly during meiosis. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause significant clinical effects.

OMIM ResearchSummary from RefSeq, UniProt

Enables DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in several processes, including negative regulation of angiogenesis; negative regulation of blood vessel endothelial cell differentiation; and positive regulation of vascular associated smooth muscle cell proliferation. Located in fibrillar center and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM 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

0.24

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.998

Z-score 4.76

OE 0.09 (0.04–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.82Z-score

OE missense 0.87 (0.79–0.96)

285 obs / 327.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.24)

0≤0.351.4

Missense OE?0.87 (0.79–0.96)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 3 / 32.1Missense obs/exp: 285 / 327.0Syn Z: 0.08

Background carrier burden — how many people carry a rare variant somewhere in FOXJ2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

720 rare PASS variants

Rare truncating (LoF)

1 in 7,500

46 rare PASS variants

Rare synonymous (reference)

1 in 160

294 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FOXJ2. 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 150	1 in 7,500
South Asian	~43k	1 in 99	1 in 8,500
Remaining (unassigned)	~30k	1 in 83	≈ 1 in 10,000
European (Finnish)	~27k	1 in 450	≈ 1 in 27,000
Admixed American	~22k	1 in 93	≈ 1 in 5,700
African / African American	~21k	1 in 88	1 in 2,500
East Asian	~20k	1 in 110	≈ 1 in 9,800
Ashkenazi Jewish	~13k	1 in 300	none seen
Middle Eastern	~2,884	1 in 120	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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓