FMNL2

protein-coding

formin like 2, the group of Formins|Armadillo like helical domain containing

Gene summary

This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. Alternatively spliced transcript variants encoding different isoforms have been described but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

Previous symbols:

FHOD2

MANE transcript

NM_052905.4

Inheritance

ClinVar variants

P:1U:130B:5

Top phenotype

FMNL2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr2:152,335,174-152,649,826

External References & Databases

Ensembl (ENSG00000157827)

Transcript & Mutation Effects

hg38 • Region Span ~314.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inflammatory bowel diseaseLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005265

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FMNL2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 11

FMNL2-related disorderTotal: 3

Mycotic Aneurysm, IntracranialTotal: 1

Crohn diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052905.4. 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	2 clinvar		3
missense		1 clinvar	119 clinvar	2 clinvar	1 clinvar	123
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	1	130	4	1	136

Highest pathogenic variant AF is 6.843194e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052905.4	RefSeq	NP_443137.2	26	MANE Select
ENST00000288670.14	Ensembl	ENSP00000288670.9	26	MANE Select
ENST00000475377.3	Ensembl	ENSP00000418959.3	27	Standard
ENST00000475377.4	Ensembl	ENSP00000418959.3	27	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in squamous cell - TarBase
EMT transition in Colorectal Cancer

Biological Process

cytoskeleton organization
regulation of cell morphogenesis
cortical actin cytoskeleton organization

Molecular Function

actin binding
Rho GTPase binding
cadherin binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000288670
Coding exons: 26
Length: 314598
Individuals with no LoFs: 124731
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 124744
p: 0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.86	375	566	0.662	0.0000292	7135
Missense (PolyPhen)		38	84.406	0.45021		1112
Synonymous	1.71	179	210	0.850	0.0000110	2032
Loss of Function	5.72	9	54.6	0.165	0.00000277	719

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000056	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000046	0.000044	rare
South Asian	0.000066	0.000065	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics. {ECO:0000269|PubMed:21834987}.;

Intolerance Scores

LoFtool: 0.156
RVIS EVS: 0.14
RVIS percentile EVS: 63.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.874

Gene Damage Prediction

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