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…

ARLOEUF 0.611 OMIM phenotype

Clinical Summary— FLII

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Gene-Disease Validity (ClinGen)

cardiomyopathy, dilated, 2j · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 213 VUS of 299 total submissions

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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

ClinVar Variant Classifications

299 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS213

Likely Benign34

Benign10

Conflicting1

Pathogenic

Likely Pathogenic

213

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	2	1	0	0	3
VUS	1	212	0	0	213
Likely Benign	0	7	4	23	34
Benign	0	2	3	5	10
Conflicting	—				1
Total	4	223	7	28	263

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

View in ClinVar →

116 pathogenic / likely-pathogenic (of 122) ClinVar copy-number / structural variants overlap FLII — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →