FOXK2

protein-coding

forkhead box K2, the group of Forkhead boxes

Gene summary

The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements. [provided by RefSeq, Jul 2008]

Previous symbols:

ILF
ILF1

MANE transcript

NM_004514.4

Inheritance

—

ClinVar variants

U:124B:27

Top phenotype

Premature ovarian insufficiency

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr17:82,519,713-82,644,662

External References & Databases

Ensembl (ENSG00000141568)

Transcript & Mutation Effects

hg38 • Region Span ~124.9 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 FOXK2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 28

Premature ovarian insufficiencyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004514.4. 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			3 clinvar	8 clinvar	8 clinvar	19
missense			120 clinvar	6 clinvar	2 clinvar	128
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar	2 clinvar	1 clinvar	4
Total	0	0	124	16	11	151

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004514.4	RefSeq	NP_004505.2	9	MANE Select
ENST00000335255.10	Ensembl	ENSP00000335677.5	9	MANE Select
ENST00000473637.6	Ensembl	ENSP00000436108.2	9	Standard
ENST00000526383.2	Ensembl	ENSP00000432663.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
UCH proteinases
Deubiquitination

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription, DNA-templated
regulation of transcription by RNA polymerase II
protein deubiquitination
positive regulation of transcription by RNA polymerase II

Molecular Function

magnesium ion binding
transcription regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335255
Coding exons: 9
Length: 124950
Individuals with no LoFs: 125515
Homozygous LoFs: 9
Heterozygous LoFs: 215
Defined: 125739
p: 0.000891

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.396	364	386	0.943	0.0000240	4173
Missense (PolyPhen)		67	118.82	0.56387		1378
Synonymous	-2.65	227	182	1.25	0.0000132	1464
Loss of Function	3.05	7	22.7	0.309	0.00000115	261

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0019	0.0016	notable
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0045	0.0041	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00025	rare
South Asian	0.0027	0.0026	notable
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta- catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). {ECO:0000269|PubMed:1339390, ECO:0000269|PubMed:1909027, ECO:0000269|PubMed:25805136}.;

Recessive Scores

pRec: 0.204

Intolerance Scores

LoFtool: 0.0444
RVIS EVS: -0.42
RVIS percentile EVS: 25.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.938

Gene Damage Prediction

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