FOXD4L3

Summary

FOXD4L3 (forkhead box D4 like 3, HGNC:18523) is a protein-coding gene on chromosome 9q21.11, encoding Forkhead box protein D4-like 3 (Q6VB84).

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 286380 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 119 total
• MANE Select transcript: NM_199135

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18523
Approved symbol	FOXD4L3
Name	forkhead box D4 like 3
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Aliases	OTTHUMG00000019959, FOXD6
Ensembl gene	ENSG00000187559
Ensembl biotype	protein_coding
OMIM	611086
Entrez	286380

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000342833

RefSeq mRNA: 1 — MANE Select: NM_199135 NM_199135

CCDS: CCDS43833

Canonical transcript exons

ENST00000342833 — 1 exons

Exon	Start	End
ENSE00001702443	68302867	68305084

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 68.18.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	68.18	gold quality
superior frontal gyrus	UBERON:0002661	58.61	gold quality
primary visual cortex	UBERON:0002436	52.47	gold quality
Ammon’s horn	UBERON:0001954	50.21	gold quality
right frontal lobe	UBERON:0002810	49.78	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	49.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	48.56	gold quality
cerebral cortex	UBERON:0000956	47.71	gold quality
frontal cortex	UBERON:0001870	47.23	gold quality
granulocyte	CL:0000094	45.39	silver quality
prefrontal cortex	UBERON:0000451	45.13	gold quality
anterior cingulate cortex	UBERON:0009835	44.82	gold quality
lower esophagus mucosa	UBERON:0035834	44.55	silver quality
cerebellar hemisphere	UBERON:0002245	43.93	gold quality
cerebellar cortex	UBERON:0002129	43.61	gold quality
cerebellum	UBERON:0002037	43.57	gold quality
putamen	UBERON:0001874	43.47	gold quality
brain	UBERON:0000955	43.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	42.92	silver quality
nucleus accumbens	UBERON:0001882	42.49	gold quality
ganglionic eminence	UBERON:0004023	41.17	gold quality
colonic epithelium	UBERON:0000397	41.11	gold quality
caudate nucleus	UBERON:0001873	41.00	gold quality
bone marrow cell	CL:0002092	39.92	gold quality
stromal cell of endometrium	CL:0002255	39.33	gold quality
temporal lobe	UBERON:0001871	39.32	gold quality
lymph node	UBERON:0000029	39.06	gold quality
amygdala	UBERON:0001876	38.94	gold quality
substantia nigra	UBERON:0002038	38.26	gold quality
hypothalamus	UBERON:0001898	37.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• The molecular landscape of well differentiated retroperitoneal liposarcoma. (PMID:34156092)

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), FOXD4L4 (ENSG00000184659), FOXD2 (ENSG00000186564), FOXI2 (ENSG00000186766), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein D4-like 3 — Q6VB84 (reviewed: Q6VB84)

All UniProt accessions (1): Q6VB84

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

RefSeq proteins (1): NP_954586* (*=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 (12 total): sequence conflict 6, region of interest 2, compositionally biased region 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6VB84-F1	57.01	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): BENPORATH_ES_WITH_H3K27ME3, chr9q21, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR302C_5P, MIR3143, MIR507, MIR557, MIR4517, MIR4267, MIR9500, MIR142_3P, MIR329_5P, MIR31_5P, MIR6768_3P

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

446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXD4L3	ANKRD20A2P	Q5SQ80	608
FOXD4L3	OR13C3	Q8NGS6	480
FOXD4L3	OR13C4	Q8NGS5	478
FOXD4L3	ZNF595	Q8IYB9	450
FOXD4L3	MAP10	Q9P2G4	419
FOXD4L3	GOLGA6L10	A6NI86	417
FOXD4L3	ANKDD1B	A6NHY2	380
FOXD4L3	FOXR2	Q6PJQ5	374
FOXD4L3	ARHGEF5	Q12774	348
FOXD4L3	MYO18B	Q8IUG5	333
FOXD4L3	DUSP19	Q8WTR2	317
FOXD4L3	RPL3L	Q92901	305
FOXD4L3	MUC12	Q9UKN1	299
FOXD4L3	NBPF1	Q3BBV0	293
FOXD4L3	WIPF2	Q8TF74	290

IntAct

49 interactions, top by confidence:

A	B	Type	Score
FOXD4L3	CARD10	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS2	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	RBPMS2	psi-mi:“MI:0915”(physical association)	0.560
CALCOCO2	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	MID2	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
BEX5	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
APOC1	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L3	CARD10	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	HNRNPK	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	RBPMS2	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	PNMA1	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	MDFI	psi-mi:“MI:0915”(physical association)	0.000
FOXD4L3	KRTAP12-2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), FOXD4L3 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

31 predictions. Top by Δscore:

Variant	Effect	Δscore
9:68303585:G:GT	donor_gain	0.5300
9:68303933:A:T	donor_gain	0.4600
9:68303554:G:GT	donor_gain	0.4400
9:68303934:GA:G	donor_gain	0.3400
9:68303878:G:GT	donor_gain	0.3300
9:68303906:G:GT	donor_gain	0.3300
9:68303935:A:AG	donor_gain	0.3200
9:68303936:G:GG	donor_gain	0.3200
9:68303906:G:T	donor_gain	0.2800
9:68303912:G:GT	donor_gain	0.2700
9:68303812:C:T	donor_gain	0.2600
9:68304047:A:AG	acceptor_gain	0.2500
9:68304048:G:GG	acceptor_gain	0.2500
9:68304069:A:G	acceptor_gain	0.2500
9:68303930:T:TG	donor_gain	0.2400
9:68303939:T:TG	donor_gain	0.2400
9:68303956:G:T	donor_gain	0.2400
9:68304451:A:AG	acceptor_gain	0.2400
9:68304451:AAAAT:A	acceptor_gain	0.2400
9:68303586:G:T	donor_gain	0.2300
9:68303905:G:GT	donor_gain	0.2300
9:68303028:A:AG	donor_gain	0.2200
9:68303067:TGG:T	donor_gain	0.2200
9:68303801:A:T	donor_gain	0.2200
9:68303051:G:GT	donor_gain	0.2100
9:68303078:G:GT	donor_gain	0.2100
9:68303856:ACTT:A	donor_gain	0.2100
9:68303547:GGC:G	donor_gain	0.2000
9:68303548:GCG:G	donor_gain	0.2000
9:68303883:C:T	donor_gain	0.2000

AlphaMissense

2679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:68303405:T:A	W152R	1.000
9:68303405:T:C	W152R	1.000
9:68303407:G:C	W152C	1.000
9:68303407:G:T	W152C	1.000
9:68303418:T:A	I156N	1.000
9:68303423:C:G	H158D	1.000
9:68303447:T:C	F166L	1.000
9:68303448:T:C	F166S	1.000
9:68303448:T:G	F166C	1.000
9:68303449:C:A	F166L	1.000
9:68303449:C:G	F166L	1.000
9:68303497:G:C	W182C	1.000
9:68303497:G:T	W182C	1.000
9:68303360:T:C	F137L	0.999
9:68303362:C:A	F137L	0.999
9:68303362:C:G	F137L	0.999
9:68303375:T:C	F142L	0.999
9:68303377:C:A	F142L	0.999
9:68303377:C:G	F142L	0.999
9:68303418:T:C	I156T	0.999
9:68303418:T:G	I156S	0.999
9:68303425:C:A	H158Q	0.999
9:68303425:C:G	H158Q	0.999
9:68303426:A:G	N159D	0.999
9:68303428:C:A	N159K	0.999
9:68303428:C:G	N159K	0.999
9:68303430:T:A	L160H	0.999
9:68303430:T:C	L160P	0.999
9:68303439:A:T	N163I	0.999
9:68303440:C:A	N163K	0.999

dbSNP variants (sampled 300 via entrez): RS10120724 (9:68302311 A>G), RS10781365 (9:68303626 C>A,G,T), RS112954110 (9:68303578 G>A,C), RS1133715 (9:68305303 C>A,G,T), RS1156686607 (9:68305504 G>A,T), RS1156811325 (9:68305078 G>C), RS1157494051 (9:68301338 G>A), RS1158405593 (9:68304407 A>G), RS1158578372 (9:68304174 C>A,T), RS1158648287 (9:68303793 C>A), RS1158808454 (9:68303200 C>G,T), RS1159063178 (9:68302710 G>A), RS1159074225 (9:68301746 T>A,C), RS1159136014 (9:68301582 C>G), RS1159638526 (9:68302274 A>G)

Disease associations

OMIM: gene MIM:611086 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
Calcitriol	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1Y5	SEES3-1V human FOXD4L3, clone1	Embryonic stem cell	Male
CVCL_A1Y6	SEES3-1V human FOXD4L3, clone2	Embryonic stem cell	Male
CVCL_A1Y7	SEES3-1V human FOXD4L3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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