FOXD2

Chr 1

forkhead box D2

Also known as: FKHL17, FREAC-9, FREAC9

NCBI Gene: 2306 ENSG00000186564 UniProt: O60548 OMIM: 602211

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 1.31

Clinical Summary— FOXD2

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 82 VUS of 90 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.029

Z-score 1.09

OE 0.51 (0.23–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.00Z-score

OE missense 0.79 (0.69–0.91)

148 obs / 186.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.23–1.31)

0≤0.351.4

Missense OE?0.79 (0.69–0.91)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 3 / 5.9Missense obs/exp: 148 / 186.4Syn Z: -1.18

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS82

Likely Benign5

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	0	1	0	1
VUS	0	82	0	82
Likely Benign	0	2	3	5
Benign	0	1	0	1
Total	1	86	3	90

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap FOXD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →