FOXJ2

Chr 12

forkhead box J2

Also known as: FHX

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
43
P/LP submissions
0%
P/LP missense
0.24
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryFOXJ2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 85 VUS of 138 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.998
Z-score 4.76
OE 0.09 (0.040.24)
Highly constrained

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

Missense Constraint
0.82Z-score
OE missense 0.87 (0.790.96)
285 obs / 327.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.040.24)
00.351.4
Missense OE0.87 (0.790.96)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 3 / 32.1Missense obs/exp: 285 / 327.0Syn Z: 0.08
DN
0.3594th %ile
GOF
0.3491th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

138 submitted variants in ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic2
VUS85
Likely Benign3
40
Pathogenic
2
Likely Pathogenic
85
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
40
0
40
Likely Pathogenic
0
0
2
0
2
VUS
0
78
7
0
85
Likely Benign
0
1
2
0
3
Benign
0
0
0
0
0
Total079510130

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FOXJ2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →