FHOD3

formin homology 2 domain containing 3, the group of Formins|Armadillo like helical domain containing

Basic information

Region (hg38): 18:36297713-36780220

Links

ENSG00000134775 ∙ NCBI:80206 ∙ OMIM:609691 ∙ HGNC:26178 ∙ Uniprot:Q2V2M9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiomyopathy, familial hypertrophic, 28 (Strong), mode of inheritance: AD
• cardiomyopathy, familial hypertrophic, 28 (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic, 28	AD	Cardiovascular	The condition can include cardiomyopathy and/or arrhthymias, and awareness may allow early diagnosis and management	Cardiovascular	30442288; 31742804; 32335906

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FHOD3 gene.

• Inborn_genetic_diseases (180 variants)
• not_provided (79 variants)
• not_specified (67 variants)
• Cardiomyopathy,_familial_hypertrophic,_28 (39 variants)
• Cardiovascular_phenotype (28 variants)
• FHOD3-related_disorder (21 variants)
• Hypertrophic_cardiomyopathy (11 variants)
• Primary_dilated_cardiomyopathy (2 variants)
• Cardiomyopathy (1 variants)
• Spinal_muscular_atrophy,_infantile,_James_type (1 variants)
• Hypertrophic_cardiomyopathy_7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FHOD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001281740.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	29	12	43
missense		2	238	33	2	275
nonsense			4		1	5
start loss						0
frameshift			2			2
splice donor/acceptor (+/-2bp)		3	3			6
Total	0	5	249	62	15

Highest pathogenic variant AF is 0.0000032558783

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FHOD3	protein_coding	protein_coding	ENST00000257209	25	482342

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0665	0.933	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.876	742	812	0.913	0.0000470	9331
Missense in Polyphen		330	375.33	0.87922		4462
Synonymous	-0.282	350	343	1.02	0.0000216	2849
Loss of Function	5.63	16	65.0	0.246	0.00000344	794

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000270	0.000270
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000950	0.0000924
European (Non-Finnish)	0.000198	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.000419	0.000294
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Actin-organizing protein that may cause stress fiber formation together with cell elongation (By similarity). Isoform 4 may play a role in actin filament polymerization in cardiomyocytes. {ECO:0000250, ECO:0000269|PubMed:21149568}.

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.569
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.22

Haploinsufficiency Scores

• pHI: 0.228
• hipred: Y
• hipred_score: 0.544
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.152

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fhod3
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: actin filament organization;negative regulation of actin filament polymerization;sarcomere organization;cardiac myofibril assembly
• Cellular component: striated muscle thin filament;Z disc
• Molecular function: actin binding;protein binding