FOXD2

Chr 1

forkhead box D2

Also known as: FKHL17, FREAC-9, FREAC9

FOXD2 encodes a forkhead domain transcription factor involved in embryonic development and body formation. Mutations cause autosomal dominant intellectual disability with variable features that may include seizures, autism spectrum disorder, and developmental delays. The gene shows relatively low constraint to loss-of-function variants, consistent with the variable expressivity observed in affected individuals.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.31
Clinical SummaryFOXD2
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 83 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.029
Z-score 1.09
OE 0.51 (0.231.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.00Z-score
OE missense 0.79 (0.690.91)
148 obs / 186.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.231.31)
00.351.4
Missense OE0.79 (0.690.91)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 3 / 5.9Missense obs/exp: 148 / 186.4Syn Z: -1.18

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic4
VUS83
Likely Benign6
Benign1
Conflicting1
5
Pathogenic
4
Likely Pathogenic
83
VUS
6
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
4
0
5
Likely Pathogenic
0
1
3
0
4
VUS
0
82
1
0
83
Likely Benign
0
2
1
3
6
Benign
0
1
0
0
1
Conflicting
1
Total18693100

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXD2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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