CFL1

Chr 11

cofilin 1

Also known as: CFL, HEL-S-15, cofilin

NCBI Gene: 1072 ENSG00000172757 UniProt: P23528

The encoded protein binds to and depolymerizes filamentous actin (F-actin) in a pH-dependent manner, playing essential roles in actin cytoskeleton regulation, cell division, and neural development. Mutations cause nemaline myopathy with early childhood onset, characterized by muscle weakness and structural abnormalities in muscle fibers. The condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.[supplied by OMIM, Apr 2004]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.72LOEUF

pLI 0.556

Z-score 2.03

OE 0.15 (0.05–0.72)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

2.80Z-score

OE missense 0.21 (0.15–0.30)

21 obs / 99.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.05–0.72)

0≤0.351.4

Missense OE?0.21 (0.15–0.30)

0≤0.61.4

Synonymous OE?1.60

0≤1.21.6

LoF obs/exp: 1 / 6.6Missense obs/exp: 21 / 99.6Syn Z: -3.09

Background carrier burden — how many people carry a rare variant somewhere in CFL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 400

123 rare PASS variants

Rare truncating (LoF)

1 in 6,900

25 rare PASS variants

Rare synonymous (reference)

1 in 300

140 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CFL1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,100	1 in 6,000
South Asian	~43k	1 in 870	≈ 1 in 20,000
Remaining (unassigned)	~30k	1 in 1,500	1 in 3,200
European (Finnish)	~27k	1 in 1,300	≈ 1 in 13,000
Admixed American	~22k	1 in 690	≈ 1 in 18,000
African / African American	~21k	1 in 3,700	≈ 1 in 17,000
East Asian	~20k	1 in 1,500	≈ 1 in 9,700
Middle Eastern	~2,884	≈ 1 in 710	≈ 1 in 2,900

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.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓