FOXD4

protein-coding

forkhead box D4, the group of Forkhead boxes

Gene summary

This gene encodes a member of the forkhead/winged helix-box (FOX) family of transcription factors. FOX transcription factors play critical roles in the regulation of multiple processes including metabolism, cell proliferation and gene expression during ontogenesis. Mutations in this gene are associated with a complex phenotype consisting of dilated cardiomyopathy, obsessive-compulsive disorders, and suicidality. [provided by RefSeq, Mar 2012]

Previous symbols:

FKHL9

MANE transcript

NM_207305.5

Inheritance

—

ClinVar variants

U:117B:62

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.29

Max pathogenic AF

—

Genomic locus

chr9:116,231-118,417

External References & Databases

Ensembl (ENSG00000170122)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 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 FOXD4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 178

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207305.5. 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				30 clinvar		30
missense			117 clinvar	31 clinvar		148
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	0	0	117	62	0	179

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207305.5	RefSeq	NP_997188.2	1	MANE Select
ENST00000382500.4	Ensembl	ENSP00000371940.2	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
anatomical structure morphogenesis
cell differentiation

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription factor activity
DNA binding, bending
sequence-specific DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000382500
Coding exons: 1
Length: 2181
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-4.07	418	240	1.74	0.0000119	2710
Missense (PolyPhen)		119	62.826	1.8941		771
Synonymous	-4.84	171	107	1.59	0.00000546	972
Loss of Function	-0.626	7	5.43	1.29	2.45e-7	56

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.239
RVIS EVS: 0.89
RVIS percentile EVS: 89.14

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0805

Gene Damage Prediction

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