FOXD4L4

Summary

FOXD4L4 (forkhead box D4 like 4, HGNC:23762) is a protein-coding gene on chromosome 9q21.11, encoding Forkhead box protein D4-like 4 (Q8WXT5).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in chromatin.

Source: NCBI Gene 349334 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_199244

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23762
Approved symbol	FOXD4L4
Name	forkhead box D4 like 4
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Aliases	bA460E7.2, OTTHUMG00000013337, OTTHUMG00000066752
Ensembl gene	ENSG00000184659
Ensembl biotype	protein_coding
OMIM	611085
Entrez	349334

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377413

RefSeq mRNA: 1 — MANE Select: NM_199244 NM_199244

CCDS: CCDS75845

Canonical transcript exons

ENST00000377413 — 1 exons

Exon	Start	End
ENSE00001771836	65737146	65738396

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 54.22.

Top tissues by expression

89 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	54.22	gold quality
stromal cell of endometrium	CL:0002255	53.53	gold quality
superior frontal gyrus	UBERON:0002661	51.04	gold quality
cortical plate	UBERON:0005343	48.24	silver quality
cerebellum	UBERON:0002037	47.00	silver quality
cerebellar cortex	UBERON:0002129	46.92	silver quality
cerebellar hemisphere	UBERON:0002245	46.80	silver quality
right hemisphere of cerebellum	UBERON:0014890	45.75	silver quality
Ammon’s horn	UBERON:0001954	45.61	gold quality
prefrontal cortex	UBERON:0000451	45.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	45.33	gold quality
frontal cortex	UBERON:0001870	45.16	gold quality
primary visual cortex	UBERON:0002436	44.71	silver quality
cerebral cortex	UBERON:0000956	44.59	gold quality
bone marrow cell	CL:0002092	44.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	44.42	gold quality
nucleus accumbens	UBERON:0001882	44.38	gold quality
ventricular zone	UBERON:0003053	44.29	silver quality
right frontal lobe	UBERON:0002810	43.99	gold quality
granulocyte	CL:0000094	43.82	silver quality
ganglionic eminence	UBERON:0004023	43.57	gold quality
brain	UBERON:0000955	42.43	gold quality
anterior cingulate cortex	UBERON:0009835	42.03	gold quality
tonsil	UBERON:0002372	42.01	gold quality
tibial nerve	UBERON:0001323	41.61	gold quality
caudate nucleus	UBERON:0001873	41.52	gold quality
putamen	UBERON:0001874	41.41	gold quality
lower esophagus mucosa	UBERON:0035834	40.85	silver quality
hypothalamus	UBERON:0001898	40.60	gold quality
skeletal muscle tissue	UBERON:0001134	39.70	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Foxd4	ENSMUSG00000051490

Paralogs (41): FOXP3 (ENSG00000049768), FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXM1 (ENSG00000111206), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), FOXJ1 (ENSG00000129654), FOXK2 (ENSG00000141568), FOXO1 (ENSG00000150907), FOXH1 (ENSG00000160973), FOXQ1 (ENSG00000164379), FOXK1 (ENSG00000164916), FOXD4 (ENSG00000170122), FOXA3 (ENSG00000170608), FOXB1 (ENSG00000171956), FOXR1 (ENSG00000176302), FOXL1 (ENSG00000176678), FOXC2 (ENSG00000176692), FOXE1 (ENSG00000178919), FOXS1 (ENSG00000179772), FOXL2 (ENSG00000183770), FOXO4 (ENSG00000184481), FOXD4L1 (ENSG00000184492), FOXD2 (ENSG00000186564), FOXI2 (ENSG00000186766), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein D4-like 4 — Q8WXT5 (reviewed: Q8WXT5)

Alternative names: Forkhead box protein D4-like 2, Forkhead box protein D4B, Myeloid factor-gamma

All UniProt accessions (1): Q8WXT5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

RefSeq proteins (1): NP_954714* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR018122	TF_fork_head_CS_1	Conserved_site
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR050211	FOX_domain-containing	Family

Pfam: PF00250

UniProt features (7 total): region of interest 2, compositionally biased region 2, chain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXT5-F1	57.50	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 15 (showing top): BENPORATH_ES_WITH_H3K27ME3, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, chr9q21, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_UP, HE_LIM_SUN_FETAL_LUNG_C2_ADC_1_CELL, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOCC_CHROMATIN, ACEVEDO_LIVER_CANCER_DN, BENPORATH_EED_TARGETS, BENPORATH_PRC2_TARGETS, BENPORATH_SUZ12_TARGETS

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), anatomical structure morphogenesis (GO:0009653), cell differentiation (GO:0030154), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
developmental process	1
anatomical structure development	1
cellular developmental process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXD4L4	OR13C3	Q8NGS6	542
FOXD4L4	OR13C4	Q8NGS5	524
FOXD4L4	MAP10	Q9P2G4	417
FOXD4L4	DUSP19	Q8WTR2	359
FOXD4L4	HIC2	Q96JB3	359
FOXD4L4	RPL3L	Q92901	345
FOXD4L4	PRB4	P02813	325
FOXD4L4	PCDHB9	Q9Y5E1	324
FOXD4L4	GTF2A1	P52655	316
FOXD4L4	FOXR2	Q6PJQ5	290
FOXD4L4	DMRT3	Q9NQL9	281
FOXD4L4	DMRT2	Q9Y5R5	279
FOXD4L4	KIAA1958	Q8N8K9	276
FOXD4L4	DMRT1	Q9Y5R6	276
FOXD4L4	SERF1A	O75920	270

IntAct

4 interactions, top by confidence:

A	B	Type	Score
FOXD4L4	MAPRE3	psi-mi:“MI:0915”(physical association)	0.560
MAPRE3	FOXD4L4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): FOXD4L4 (Two-hybrid)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0JNN8, A6NF83, A6NHQ4, A6QPM6, A8E4L3, A8MTW9, B2KGE5, C9JVW0, I3L1E1, O43541, O75474, O75638, P0C7X2, P70339, P89439, Q02080, Q05215, Q12950, Q3SYB3, Q5T230, Q5VV16, Q6NZ36, Q6NZY7, Q6P1X6, Q6VB84, Q6VUC0, Q6VUP9, Q6ZSJ8, Q7RTU5, Q7TNS8, Q80WY3, Q86SI9, Q86UU5, Q8K025

Diamond homologs: A0A078BQN7, A0A1W2PRP0, A0A8V0YY16, A1L1S5, A3KNJ3, A8MTJ6, A8XJN7, B5RHS5, D3Z120, F1R8Z9, O00358, O17617, O43638, O54743, O60129, O88470, P32027, P32028, P32030, P32315, P42128, P55316, P56260, P58012, P79772, P85037, P91278, Q00939, Q01167, Q02360, Q12946, Q12947, Q12948, Q12950, Q12951, Q12952, Q13461, Q19802, Q1A1A1, Q1A1A2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

0 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2674 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:65737641:T:C	F166L	1.000
9:65737642:T:C	F166S	1.000
9:65737642:T:G	F166C	1.000
9:65737643:C:A	F166L	1.000
9:65737643:C:G	F166L	1.000
9:65737691:G:C	W182C	1.000
9:65737691:G:T	W182C	1.000
9:65737554:T:C	F137L	0.999
9:65737556:C:A	F137L	0.999
9:65737556:C:G	F137L	0.999
9:65737569:T:C	F142L	0.999
9:65737571:C:A	F142L	0.999
9:65737571:C:G	F142L	0.999
9:65737599:T:A	W152R	0.999
9:65737599:T:C	W152R	0.999
9:65737601:G:C	W152C	0.999
9:65737601:G:T	W152C	0.999
9:65737612:T:A	I156N	0.999
9:65737617:C:G	H158D	0.999
9:65737619:C:A	H158Q	0.999
9:65737619:C:G	H158Q	0.999
9:65737622:C:A	N159K	0.999
9:65737622:C:G	N159K	0.999
9:65737624:T:A	L160H	0.999
9:65737624:T:C	L160P	0.999
9:65737633:A:T	N163I	0.999
9:65737689:T:A	W182R	0.999
9:65737689:T:C	W182R	0.999
9:65737719:T:C	F192L	0.999
9:65737720:T:G	F192C	0.999

dbSNP variants (sampled 300 via entrez): RS10796795 (9:65737984 G>C), RS11263204 (9:65736157 C>A,G), RS11263205 (9:65735889 T>G), RS11263206 (9:65735843 C>G), RS11263207 (9:65735804 C>A,T), RS11263208 (9:65735516 C>G,T), RS1156649699 (9:65735545 G>A), RS1157164734 (9:65738435 C>T), RS1157695951 (9:65735809 CAAAAAAA>C,CA,CAA,CAAA,CAAAA,CAAAAA,CAAAAAA,CAAAAAAAA,CAAAAAAAAA,CAAAAAAAAAA,CAAAAAAAAAAA), RS1157793211 (9:65737807 T>C), RS1158322043 (9:65737316 G>A,C,T), RS1158783841 (9:65736863 T>C), RS1158840262 (9:65736224 A>C,G), RS1158991008 (9:65738424 G>A), RS1159207892 (9:65737275 G>A,C)

Disease associations

OMIM: gene MIM:611085 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
Atrazine	increases expression	1
Diazinon	increases methylation	1
Smoke	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1Y8	SEES3-1V human FOXD4L4, clone1	Embryonic stem cell	Male
CVCL_A1Y9	SEES3-1V human FOXD4L4, clone2	Embryonic stem cell	Male
CVCL_A1Z0	SEES3-1V human FOXD4L4, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.