CFL1

protein-coding

cofilin 1

Gene summary

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]

Previous symbols:

MANE transcript

NM_005507.3

Inheritance

—

ClinVar variants

U:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr11:65,823,022-65,862,026

External References & Databases

Ensembl (ENSG00000172757)

Transcript & Mutation Effects

hg38 • Region Span ~39.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFL1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005507.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			8 clinvar			8
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	13	0	0	13

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005507.3	RefSeq	NP_005498.1	4	MANE Select
ENST00000308162.10	Ensembl	ENSP00000309629.5	4	MANE Select
ENST00000524553.5	Ensembl	ENSP00000432226.1	3	Standard
ENST00000525451.6	Ensembl	ENSP00000432660.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cfl1	Danio rerio	Structure: mesonephric podocyte Quality: structure abnormal

Gene / Model

Organism

Observed Phenotype

cfl1

Danio rerio

Structure: mesonephric podocyte

Quality: structure

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fc gamma R-mediated phagocytosis - Homo sapiens (human)
Pertussis - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Axon guidance - Homo sapiens (human)
Brain-Derived Neurotrophic Factor (BDNF) signaling pathway

Biological Process

mitotic cytokinesis
neural crest cell migration
neural fold formation
protein phosphorylation
cytoskeleton organization

Molecular Function

signaling receptor binding
protein binding
actin filament binding

Cellular Component

extracellular space
nucleus
cytoplasm
cytosol
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000525451
Coding exons: 4
Length: 39005
Individuals with no LoFs: 105289
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 105290
p: 0.00000475

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.80	21	99.6	0.211	0.00000603	1090
Missense (PolyPhen)		1	16.75	0.059702		263
Synonymous	-3.09	69	43.2	1.60	0.00000296	308
Loss of Function	2.03	1	6.63	0.151	2.79e-7	95

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000052	0.000052	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. Regulates actin cytoskeleton dynamics. Important for normal progress through mitosis and normal cytokinesis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:11812157, PubMed:15580268, PubMed:21834987, PubMed:23633677). Required for neural tube morphogenesis and neural crest cell migration (By similarity). {ECO:0000250|UniProtKB:P18760, ECO:0000269|PubMed:11812157, ECO:0000269|PubMed:15580268, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:23633677}.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.123
RVIS EVS: -0.19
RVIS percentile EVS: 39.68

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.959

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium