FHOD1

protein-coding

formin homology 2 domain containing 1, the group of Formins|Armadillo like helical domain containing

Gene summary

This gene encodes a protein which is a member of the formin/diaphanous family of proteins. The gene is ubiquitously expressed but is found in abundance in the spleen. The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. It also contains a coiled-coil domain, a collagen-like domain, two nuclear localization signals, and several potential PKC and PKA phosphorylation sites. It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MANE transcript

NM_013241.3

Inheritance

—

ClinVar variants

U:213B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr16:67,229,387-67,247,481

External References & Databases

Ensembl (ENSG00000135723)

Transcript & Mutation Effects

hg38 • Region Span ~18.1 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 FHOD1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 204

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013241.3. 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			206 clinvar	7 clinvar		213
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	213	7	0	220

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013241.3	RefSeq	NP_037373.2	22	MANE Select
ENST00000258201.9	Ensembl	ENSP00000258201.4	22	MANE Select
NM_001318202.2	RefSeq	NP_001305131.1	24	Standard
ENST00000561922.1	Ensembl	ENSP00000458085.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nuclear migration
positive regulation of transcription by RNA polymerase II
regulation of stress fiber assembly
positive regulation of stress fiber assembly
establishment of centrosome localization

Molecular Function

actin binding
protein binding
protein domain specific binding
identical protein binding
protein self-association

Cellular Component

stress fiber
nucleus
cytoplasm
cytosol
intercalated disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258201
Coding exons: 22
Length: 18272
Individuals with no LoFs: 125552
Homozygous LoFs: 1
Heterozygous LoFs: 195
Defined: 125748
p: 0.000780

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.931	659	730	0.903	0.0000477	7390
Missense (PolyPhen)		287	342.71	0.83745		3500
Synonymous	1.28	273	301	0.906	0.0000182	2579
Loss of Function	2.27	33	50.4	0.655	0.00000260	567

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00025	rare
Latino/Admixed American	0.00076	0.00075	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00061	0.00060	rare
Finnish	0.0015	0.0015	notable
European (Non-Finnish)	0.00099	0.00097	rare
South Asian	0.00033	0.00033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for the assembly of F-actin structures, such as stress fibers. Depends on the Rho-ROCK cascade for its activity. Contributes to the coordination of microtubules with actin fibers and plays a role in cell elongation. Acts synergistically with ROCK1 to promote SRC-dependent non-apoptotic plasma membrane blebbing. {ECO:0000269|PubMed:14576350, ECO:0000269|PubMed:15878344, ECO:0000269|PubMed:18694941}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.918
RVIS EVS: -1.21
RVIS percentile EVS: 5.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.878

Gene Damage Prediction

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