FLII

Chr 17AR

FLII actin remodeling protein

Also known as: CMD2J, FLI, FLIL, Fli1

NCBI Gene: 2314 ENSG00000177731 UniProt: Q13045 OMIM: 600362

FLII encodes a protein that regulates actin polymerization and is required for proper myofibril organization and sarcomeric thin filament length regulation in cardiac muscle. Mutations cause autosomal recessive dilated cardiomyopathy (type 2J). The gene is highly constrained against loss-of-function variants (LOEUF 0.607), suggesting complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein with a gelsolin-like actin binding domain and an N-terminal leucine-rich repeat-protein protein interaction domain. The protein is similar to a Drosophila protein involved in early embryogenesis and the structural organization of indirect flight muscle. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 2JMIM #620635

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · cardiomyopathy, dilated, 2j · AR · ClinGen 2026

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.61

LOEUF

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.000

Z-score 4.23

OE 0.45 (0.34–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.51Z-score

OE missense 0.95 (0.89–1.01)

753 obs / 793.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.34–0.61)

0≤0.351.4

Missense OE?0.95 (0.89–1.01)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 31 / 68.9Missense obs/exp: 753 / 793.2Syn Z: -1.97

Background carrier burden — how many people carry a rare variant somewhere in FLII?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 32

1,924 rare PASS variants

Rare truncating (LoF)

1 in 300

291 rare PASS variants

Rare synonymous (reference)

1 in 54

827 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FLII. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 39	1 in 300
South Asian	~43k	1 in 24	1 in 270
Remaining (unassigned)	~30k	1 in 26	1 in 200
European (Finnish)	~27k	1 in 98	1 in 1,200
Admixed American	~22k	1 in 28	1 in 590
African / African American	~21k	1 in 23	1 in 890
East Asian	~20k	1 in 28	1 in 1,100
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 4,100
Middle Eastern	~2,884	1 in 30	1 in 460

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.