The protein functions as a DNA-binding transcription factor that regulates gene expression by RNA polymerase II and is involved in cell differentiation and anatomical structure development. Mutations in this gene have been associated with neurodevelopmental disorders, though the clinical phenotype and inheritance pattern are not well-established in the current literature. The gene shows moderate tolerance to loss-of-function variants based on population genetics data.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 1.39
Clinical SummaryFOXD4L3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.39LOEUF
pLI 0.495
Z-score 1.28
OE 0.00 (0.001.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.68Z-score
OE missense 1.62 (1.371.89)
95 obs / 58.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.001.39)
00.351.4
Missense OE1.62 (1.371.89)
00.61.4
Synonymous OE1.33
01.21.6
LoF obs/exp: 0 / 1.9Missense obs/exp: 95 / 58.7Syn Z: -1.34
DN
0.7132th %ile
GOF
0.5562th %ile
LOF
0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FOXD4L3 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found