FERD3L

Chr 7

Fer3 like bHLH transcription factor

Also known as: N-TWIST, NATO3, NTWIST, PTFB, bHLHa31

NCBI Gene: 222894ENSG00000146618UniProt: Q96RJ6

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in developmental process; negative regulation of DNA-templated transcription; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including floor plate development; regulation of dopaminergic neuron differentiation; and regulation of neurogenesis. Predicted to be located in chromatin and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

70
ClinVar variants
41
Pathogenic / LP
0.32
pLI score
0
Active trials
Clinical Summary— FERD3L
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 28 VUS of 70 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
1.12LOEUF
pLI 0.319
Z-score 1.44
OE 0.24 (0.08–1.12)
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.
-0.40Z-score
OE missense 1.11 (0.95–1.31)
110 obs / 98.7 exp
Tolerant

Tolerant to missense variation

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.0.24 (0.08–1.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.95–1.31)
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.1.44
0≤1.21.6
LoF obs/exp: 1 / 4.2Missense obs/exp: 110 / 98.7Syn Z: -2.30

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic2
VUS28
Likely Benign1
39
Pathogenic
2
Likely Pathogenic
28
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
2
0
2
VUS
0
21
7
0
28
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total02248070

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

View in ClinVar →

Protein Context — Lollipop Plot

FERD3L · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HDAC9, TWIST1 and FERD3L gene expression in asymptomatic stable and unstable carotid plaques.
Ferronato S et al.·Inflamm Res
2016
Rs10230207 genotype confers changes in HDAC9 and TWIST1, but not FERD3L in lymphoblasts from patients with intracranial aneurysm.
Lansdell TA et al.·Neurogenetics
2019Cohort
Increased detection of genetic loci associated with risk predictors of osteoporotic fracture using a pleiotropic cFDR method.
Greenbaum J et al.·Bone
2017
Saethre-Chotzen phenotype with learning disability and hyper IgE phenotype in a patient due to complex chromosomal rearrangement involving chromosomes 3 and 7.
Zechi-Ceide RM et al.·Am J Med Genet A
2012Case report
Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21).
Delplanque J et al.·Cerebellum
2008
Identification of genes targeted by CpG island methylator phenotype in neuroblastomas, and their possible integrative involvement in poor prognosis.
Abe M et al.·Oncology
2008
Contiguous gene deletion neighboring TWIST1 identified in a patient with Saethre-Chotzen syndrome associated with neurodevelopmental delay: Possible contribution of HDAC9.
Shimbo H et al.·Congenit Anom (Kyoto)
2018Case report
Y-craniosynostosis by premature fusion of the metopic and coronal sutures: a new nosological entity or a variety of Saethre-Chotzen syndrome?
di Rocco F et al.·Birth Defects Res A Clin Mol Teratol
2015Case report
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