FLII

Chr 17AR

FLII actin remodeling protein

ENSG00000177731UniProt: Q13045

Is a regulator of actin polymerization, required for proper myofibril organization and regulation of the length of sarcomeric thin filaments (By similarity). It also plays a role in the assembly of cardiomyocyte cell adhesion complexes (By similarity). Regulates cytoskeletal rearrangements involved in cytokinesis and cell migration, by inhibiting Rac1-dependent paxillin phosphorylation (By similarity). May play a role as coactivator in transcriptional activation by hormone-activated nuclear receptors (NR) and acts in cooperation with NCOA2 and CARM1 (PubMed:14966289). Involved in estrogen hormone signaling

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 2JMIM #620635
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FLII
🧬
Gene-Disease Validity (ClinGen)
cardiomyopathy, dilated, 2j · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.61LOEUF
pLI 0.000
Z-score 4.23
OE 0.45 (0.34–0.61)
Tolerant

Typical tolerance to LoF variation

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.
0.51Z-score
OE missense 0.95 (0.89–1.01)
753 obs / 793.2 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.0.45 (0.34–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.89–1.01)
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.1.14
0≤1.21.6
LoF obs/exp: 31 / 68.9Missense obs/exp: 753 / 793.2Syn Z: -1.97

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FLII · 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

Cardiomyopathy, dilated, 2J

MIM #620635

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A human FLII gene variant alters sarcomeric actin thin filament length and predisposes to cardiomyopathy.
Kuwabara Y et al.·Proc Natl Acad Sci U S A
2023
Role of FliF and FliI of Listeria monocytogenes in flagellar assembly and pathogenicity.
Bigot A et al.·Infect Immun
2005
Categorized Genetic Analysis in Childhood-Onset Cardiomyopathy.
Al-Hassnan ZN et al.·Circ Genom Precis Med
2020
Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling.
Wang T et al.·Clin Cancer Res
2016
Significance of Gelsolin Superfamily Genes in Diagnosis, Prognosis and Immune Microenvironment Regulation for Endometrial Cancer.
Jiang S et al.·Cancer Med
2025
In vitro analysis of the effect of Flightless I on murine tenocyte cellular functions.
Jackson JE et al.·J Orthop Surg Res
2020
USF1-mediated ALKBH5 stabilizes FLII mRNA in an m6A-YTHDF2-dependent manner to repress glycolytic activity in prostate adenocarcinoma.
Fu D et al.·Mol Carcinog
2023
Flightless I Alters the Inflammatory Response and Autoantibody Profile in an OVA-Induced Atopic Dermatitis Skin-Like Disease.
Kopecki Z et al.·Front Immunol
2018
Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis.
Kopecki Z et al.·Sci Rep
2019Functional
Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.
Bridge JA et al.·Am J Surg Pathol
1999Review
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.

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External Resources

Links to major genomics databases and tools