FMNL3

protein-coding

formin like 3, the group of Formins|Armadillo like helical domain containing

Gene summary

The protein encoded by this gene contains a formin homology 2 domain and has high sequence identity to the mouse Wbp3 protein. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_175736.5

Inheritance

—

ClinVar variants

U:141B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr12:49,636,499-49,708,165

External References & Databases

Ensembl (ENSG00000161791)

Transcript & Mutation Effects

hg38 • Region Span ~71.7 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 FMNL3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 129

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_175736.5. 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			2 clinvar			2
missense			133 clinvar	1 clinvar		134
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	141	1	0	142

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_175736.5	RefSeq	NP_783863.4	26	MANE Select
ENST00000335154.10	Ensembl	ENSP00000335655.5	26	MANE Select
NM_001367835.1	RefSeq	NP_001354764.1	26	Standard
NM_198900.3	RefSeq	NP_944489.2	25	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fmnl3	Danio rerio	Structure: dorsal longitudinal anastomotic vessel Quality: aplastic abnormal

Gene / Model

Organism

Observed Phenotype

fmnl3

Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: aplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
RHO GTPases Activate Formins
RHO GTPase Effectors
Signaling by Rho GTPases

Biological Process

angiogenesis
cytoskeleton organization
regulation of cell shape
cell migration
actin cytoskeleton organization

Molecular Function

actin binding
Rho GTPase binding
GTPase activating protein binding

Cellular Component

cytoplasm
Golgi apparatus
cytosol
plasma membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335154
Coding exons: 26
Length: 70225
Individuals with no LoFs: 125315
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125350
p: 0.000140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.20	449	601	0.747	0.0000372	6713
Missense (PolyPhen)		253	361.01	0.70082		4052
Synonymous	-0.635	245	233	1.05	0.0000129	2018
Loss of Function	5.30	12	54.1	0.222	0.00000289	625

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00013	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00020	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Required for developmental angiogenesis (By similarity). In this process, required for microtubule reorganization and for efficient endothelial cell elongation. In quiescent endothelial cells, triggers rearrangement of the actin cytoskeleton, but does not alter microtubule alignement. {ECO:0000250|UniProtKB:Q6NXC0, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22275430}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.214
RVIS EVS: -1.02
RVIS percentile EVS: 8.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.921

Gene Damage Prediction

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