FMN1

protein-coding

formin 1, the group of Formins

Gene summary

This gene belongs to the formin homology family and encodes a protein that has a role in the formation of adherens junction and the polymerization of linear actin cables. The homologous gene in mouse is associated with limb deformity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

Previous symbols:

MANE transcript

NM_001277313.2

Inheritance

ClinVar variants

P:1U:219B:94

Top phenotype

FMN1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr15:32,765,544-33,194,714

External References & Databases

Ensembl (ENSG00000248905)

Transcript & Mutation Effects

hg38 • Region Span ~429.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005365

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FMN1 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 315

not specifiedTotal: 219

FMN1-related disorderTotal: 49

Hereditary breast ovarian cancer syndromeTotal: 3

Breast-ovarian cancer, familial, susceptibility to, 4Total: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Hearing loss, autosomal recessiveTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001277313.2. 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			21 clinvar	35 clinvar	12 clinvar	68
missense			190 clinvar	25 clinvar	22 clinvar	237
nonsense			2 clinvar			2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	0	1	219	60	34	314

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001277313.2	RefSeq	NP_001264242.1	18	MANE Select
ENST00000616417.5	Ensembl	ENSP00000479134.1	18	MANE Select
NM_001103184.4	RefSeq	NP_001096654.1	17	Standard
NM_001277314.2	RefSeq	NP_001264243.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

E-cadherin signaling in keratinocytes

Biological Process

gene expression
forelimb morphogenesis
hindlimb morphogenesis
actin nucleation
skeletal system morphogenesis

Molecular Function

actin binding
microtubule binding
SH3 domain binding

Cellular Component

nucleus
cytoplasm
actin filament
plasma membrane
adherens junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334528
Coding exons: 17
Length: 429151
Individuals with no LoFs: 124478
Homozygous LoFs: 0
Heterozygous LoFs: 177
Defined: 124655
p: 0.000710

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.53	721	614	1.17	0.0000323	7769
Missense (PolyPhen)		111	138.21	0.80315		1867
Synonymous	-3.43	306	239	1.28	0.0000135	2316
Loss of Function	1.93	35	49.7	0.704	0.00000253	664

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00093	0.00090	rare
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.00095	0.00095	rare
Finnish	0.00061	0.00060	rare
European (Non-Finnish)	0.00061	0.00058	rare
South Asian	0.00089	0.00088	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the formation of adherens junction and the polymerization of linear actin cables. {ECO:0000250}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.991
RVIS EVS: 0.86
RVIS percentile EVS: 88.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.670

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High