FMN2

formin 2, the group of Formins

Basic information

Region (hg38): 1:240014347-240475187

Links

ENSG00000155816 ∙ NCBI:56776 ∙ OMIM:606373 ∙ HGNC:14074 ∙ Uniprot:Q9NZ56 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 47 (Strong), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 47 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive, 47	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	25480035

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FMN2 gene.

• not provided (189 variants)
• Inborn genetic diseases (59 variants)
• not specified (41 variants)
• Intellectual disability, autosomal recessive 47 (37 variants)
• Intellectual disability (1 variants)
• Neurodevelopmental abnormality (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FMN2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				133	8	141
missense		1	96	11	6	114
nonsense	2	4				6
start loss						0
frameshift	2	1				3
inframe indel			1	3	3	7
splice donor/acceptor (+/-2bp)						0
splice region			1	2	1	4
non coding			1	1		2
Total	4	6	98	148	17

Highest pathogenic variant AF is 0.00000657

Variants in FMN2

This is a list of pathogenic ClinVar variants found in the FMN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-240092109-C-T			Uncertain significance (Jan 13, 2023)
1-240092193-G-A			Likely benign (Nov 15, 2017)
1-240092201-A-G		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
1-240092257-A-C		Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
1-240092262-G-A		FMN2-related disorder	Likely benign (Oct 13, 2023)
1-240092268-GGGC-G		Intellectual disability, autosomal recessive 47	Benign (Aug 10, 2021)
1-240092270-GC-G		Aganglionic megacolon • Intellectual disability, autosomal recessive 47	Conflicting classifications of pathogenicity (May 16, 2019)
1-240092271-C-G			Likely benign (Aug 01, 2023)
1-240092277-C-A		FMN2-related disorder	Likely benign (Oct 04, 2021)
1-240092286-G-T			Likely benign (Sep 01, 2023)
1-240092335-T-A		Inborn genetic diseases	Uncertain significance (Apr 20, 2021)
1-240092379-C-T			Likely benign (Feb 05, 2018)
1-240092401-C-G		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
1-240092470-C-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
1-240092472-C-T			Benign (Dec 31, 2019)
1-240092480-C-T		not specified	Uncertain significance (Nov 09, 2015)
1-240092493-C-T			Likely benign (Jun 01, 2022)
1-240092508-C-T		not specified	Likely benign (Apr 25, 2018)
1-240092535-C-T		not specified	Benign (Dec 31, 2019)
1-240092577-C-T			Likely benign (Dec 03, 2018)
1-240092634-C-A			Likely benign (Feb 13, 2018)
1-240092640-G-A		not specified • FMN2-related disorder	Benign/Likely benign (Dec 01, 2023)
1-240092656-A-T		Intellectual disability, autosomal recessive 47	Likely pathogenic (Feb 23, 2018)
1-240092684-A-T		Intellectual disability, autosomal recessive 47 • not specified	Uncertain significance (Dec 08, 2023)
1-240092713-G-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FMN2	protein_coding	protein_coding	ENST00000319653	18	460842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00228	122940	151	2657	125748	0.0112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.318	856	883	0.970	0.0000466	10847
Missense in Polyphen		66	104.56	0.63121		1450
Synonymous	-4.80	493	375	1.32	0.0000225	3753
Loss of Function	6.11	10	61.9	0.162	0.00000322	738

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0232	0.0184
Ashkenazi Jewish	0.0147	0.00627
East Asian	0.0317	0.0141
Finnish	0.0548	0.0246
European (Non-Finnish)	0.0287	0.0129
Middle Eastern	0.0317	0.0141
South Asian	0.0107	0.00475
Other	0.0268	0.0113

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization (PubMed:22330775, PubMed:21730168). Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2 (PubMed:22330775, PubMed:21730168). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning, asymmetric oocyte division and polar body extrusion during female germ cell meiosis (By similarity). Plays a role in responses to DNA damage, cellular stress and hypoxia by protecting CDKN1A against degradation, and thereby plays a role in stress-induced cell cycle arrest (PubMed:23375502). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). Protects cells against apoptosis by protecting CDKN1A against degradation (PubMed:23375502). {ECO:0000250|UniProtKB:Q9JL04, ECO:0000269|PubMed:21730168, ECO:0000269|PubMed:22330775, ECO:0000269|PubMed:23375502, ECO:0000269|PubMed:26287480}.
• Disease: DISEASE: Mental retardation, autosomal recessive 47 (MRT47) [MIM:616193]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT47 patients show delayed development, with cognition and speech more affected than motor skills. {ECO:0000269|PubMed:25480035}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.659
• rvis_EVS: 0.41
• rvis_percentile_EVS: 76.56

Haploinsufficiency Scores

• pHI: 0.109
• hipred: Y
• hipred_score: 0.545
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.213

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fmn2
• Phenotype: reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cellular response to DNA damage stimulus;multicellular organism development;protein transport;vesicle-mediated transport;intracellular signal transduction;polar body extrusion after meiotic divisions;negative regulation of protein catabolic process;negative regulation of apoptotic process;intracellular transport;oogenesis;establishment of meiotic spindle localization;homologous chromosome movement towards spindle pole involved in homologous chromosome segregation;formin-nucleated actin cable assembly;cellular response to hypoxia;positive regulation of double-strand break repair
• Cellular component: nucleus;nucleolus;endoplasmic reticulum membrane;spindle;cytosol;plasma membrane;microvillus;cell cortex;actin cytoskeleton;cytoplasmic vesicle membrane;perinuclear region of cytoplasm
• Molecular function: molecular_function;actin binding