FOXN2

Chr 2

forkhead box N2

Also known as: HTLF

The encoded protein is a forkhead domain transcription factor that binds to purine-rich DNA sequences and regulates gene transcription. Mutations cause autosomal recessive intellectual disability with speech delay and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
13
P/LP submissions
0%
P/LP missense
0.48
LOEUF
Mechanism
Clinical SummaryFOXN2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 70 VUS of 98 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.497
Z-score 3.21
OE 0.21 (0.100.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.59Z-score
OE missense 1.11 (1.001.23)
254 obs / 229.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.21 (0.100.48)
00.351.4
Missense OE1.11 (1.001.23)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 4 / 19.2Missense obs/exp: 254 / 229.0Syn Z: -0.63

ClinVar Variant Classifications

98 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS70
Likely Benign2
Benign3
10
Pathogenic
3
Likely Pathogenic
70
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
3
0
3
VUS
1
64
5
0
70
Likely Benign
0
2
0
0
2
Benign
0
0
1
2
3
Total16619288

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXN2 · 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.

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Clinical Literature
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