FOXD2

Chr 1

forkhead box D2

Also known as: FKHL17, FREAC-9, FREAC9

NCBI Gene: 2306ENSG00000186564UniProt: O60548

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]

95
ClinVar variants
9
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— FOXD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 78 VUS of 95 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.00Z-score
OE missense 0.79 (0.69–0.91)
148 obs / 186.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.51 (0.23–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.69–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 3 / 5.9Missense obs/exp: 148 / 186.4Syn Z: -1.18

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic4
VUS78
Likely Benign6
Benign1
Conflicting1
5
Pathogenic
4
Likely Pathogenic
78
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
77
1
0
78
Likely Benign
0
2
1
3
6
Benign
0
1
0
0
1
Conflicting
—1
Total1819395

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
FORKHEAD BOX D2; FOXD2
MIM #602211 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Oncogenicity of lncRNA FOXD2-AS1 and its molecular mechanisms in human cancers.
Hu Q et al.·Pathol Res Pract
2019Review
Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).
Riedhammer KM et al.·Kidney Int
2024
FOXD2-AS1 acts an oncogene in esophageal squamous cell carcinoma through sponging miR-204-3p.
Luo D et al.·Clin Transl Oncol
2022
N(6)-methyladenosine methyltransferase WTAP-stabilized FOXD2-AS1 promotes the osteosarcoma progression through m(6)A/FOXM1 axis.
Ren Z et al.·Bioengineered
2022
FOXD2-AS1 Predicts Dismal Prognosis for Oral Squamous Cell Carcinoma and Regulates Cell Proliferation.
Liang X et al.·Cell Transplant
2020
FOXD2-AS1 promotes migration and invasion of head and neck squamous cell carcinoma and predicts poor prognosis.
Zhang L et al.·Future Oncol
2020
HIF-1α induced long noncoding RNA FOXD2-AS1 promotes the osteosarcoma through repressing p21.
Ren Z et al.·Biomed Pharmacother
2019
FOXD2-AS1 correlates with the malignant status and regulates cell proliferation, migration, and invasion in cutaneous melanoma.
Ren W et al.·J Cell Biochem
2019
Long non-coding RNA FOXD2-AS1 aggravates nasopharyngeal carcinoma carcinogenesis by modulating miR-363-5p/S100A1 pathway.
Chen G et al.·Gene
2018
Comprehensive Analysis and Experimental Validation of FOXD2 as a Novel Potential Prognostic Biomarker Associated with Immune Infiltration in Head and Neck Squamous Cell Carcinoma.
He H et al.·Curr Comput Aided Drug Des
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools