FOXP4

protein-coding

forkhead box P4, the group of MicroRNA protein coding host genes|Forkhead boxes

Gene summary

This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Many members of the forkhead box gene family, including members of subfamily P, have roles in mammalian oncogenesis. This gene may play a role in the development of tumors of the kidney and larynx. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001012426.2

Inheritance

ClinVar variants

P:4U:146B:18

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr6:41,546,381-41,602,384

External References & Databases

Ensembl (ENSG00000137166)

Transcript & Mutation Effects

hg38 • Region Span ~56.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FOXP4 variants in ClinVar

18 Conditions Cataloged

not specifiedTotal: 102

not providedTotal: 44

FOXP4-related disorderTotal: 6

Lung adenocarcinomaTotal: 5

Neurodevelopmental disorderTotal: 3

Ventricular septal defectTotal: 2

Craniofacial asymmetryTotal: 1

Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001012426.2. 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			7 clinvar	10 clinvar	2 clinvar	19
missense	1 clinvar	2 clinvar	115 clinvar	5 clinvar	1 clinvar	124
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift			11 clinvar			11
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	1	3	146	15	3	168

Highest pathogenic variant AF is 0.0000012391067

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001012426.2	RefSeq	NP_001012426.1	16	MANE Select
ENST00000307972.10	Ensembl	ENSP00000309823.4	16	MANE Select
NM_001012427.2	RefSeq	NP_001012427.1	16	Standard
NM_001405824.1	RefSeq	NP_001392753.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
protein binding
sequence-specific DNA binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373060
Coding exons: 16
Length: 55959
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125745
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.95	304	416	0.731	0.0000258	4361
Missense (PolyPhen)		95	163.72	0.58027		1737
Synonymous	-0.651	197	186	1.06	0.0000131	1363
Loss of Function	4.64	5	34.4	0.146	0.00000147	367

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor that represses lung-specific expression. {ECO:0000250}.;

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.0749
RVIS EVS: -0.95
RVIS percentile EVS: 9.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.973

Gene Damage Prediction

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