FOXD4L6

Summary

FOXD4L6 (forkhead box D4 like 6, HGNC:31986) is a protein-coding gene on chromosome 9p11.2, encoding Forkhead box protein D4-like 6 (Q3SYB3).

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 653404 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 69 total
• MANE Select transcript: NM_001085476

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31986
Approved symbol	FOXD4L6
Name	forkhead box D4 like 6
Location	9p11.2
Locus type	gene with protein product
Status	Approved
Aliases	OTTHUMG00000066822
Ensembl gene	ENSG00000273514
Ensembl biotype	protein_coding
Entrez	653404

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000622588

RefSeq mRNA: 1 — MANE Select: NM_001085476 NM_001085476

CCDS: CCDS43826

Canonical transcript exons

ENST00000622588 — 1 exons

Exon	Start	End
ENSE00003715206	41126435	41128681

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 63.58.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	63.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	59.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	59.29	gold quality
right frontal lobe	UBERON:0002810	58.10	gold quality
cerebral cortex	UBERON:0000956	55.75	gold quality
Ammon’s horn	UBERON:0001954	55.41	gold quality
frontal cortex	UBERON:0001870	55.35	gold quality
cerebellar hemisphere	UBERON:0002245	54.22	gold quality
cerebellum	UBERON:0002037	54.18	gold quality
cerebellar cortex	UBERON:0002129	54.17	gold quality
prefrontal cortex	UBERON:0000451	53.90	gold quality
anterior cingulate cortex	UBERON:0009835	53.66	gold quality
superior frontal gyrus	UBERON:0002661	53.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.86	gold quality
nucleus accumbens	UBERON:0001882	52.68	gold quality
caudate nucleus	UBERON:0001873	52.35	gold quality
putamen	UBERON:0001874	52.10	gold quality
brain	UBERON:0000955	50.61	gold quality
lower esophagus mucosa	UBERON:0035834	47.30	silver quality
mucosa of transverse colon	UBERON:0004991	46.09	gold quality
cortical plate	UBERON:0005343	45.46	gold quality
hypothalamus	UBERON:0001898	44.09	gold quality
amygdala	UBERON:0001876	43.13	gold quality
temporal lobe	UBERON:0001871	42.94	gold quality
bone marrow cell	CL:0002092	42.53	gold quality
vermiform appendix	UBERON:0001154	42.04	gold quality
ventricular zone	UBERON:0003053	41.34	gold quality
granulocyte	CL:0000094	40.85	gold quality
substantia nigra	UBERON:0002038	39.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	39.05	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

miRNA regulators (miRDB)

35 targeting FOXD4L6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-15A-3P	97.47	65.08	527
HSA-MIR-4286	97.20	64.37	1587

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), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767)

Protein

Protein identifiers

Forkhead box protein D4-like 6 — Q3SYB3 (reviewed: Q3SYB3)

All UniProt accessions (1): Q3SYB3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001078945* (*=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 (6 total): 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-Q3SYB3-F1	57.04	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): chr9p11, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR302C_5P, MIR3143, MIR4517, MIR4267, MIR9500, MIR142_3P, MIR329_5P, MIR31_5P, MIR6768_3P, MIR15A_3P, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

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

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXD4L6	OR5AP2	Q8NGF4	594
FOXD4L6	OR1L8	Q8NGR8	579
FOXD4L6	OR8B4	Q96RC9	571
FOXD4L6	ZNF684	Q5T5D7	543
FOXD4L6	FBXO48	Q5FWF7	510
FOXD4L6	OR2I1	Q8NGU4	507
FOXD4L6	ZNF793	Q6ZN11	481
FOXD4L6	NUP62CL	Q9H1M0	480
FOXD4L6	OR4D10	Q8NGI6	480
FOXD4L6	ZNF616	Q08AN1	478
FOXD4L6	DHRS4L2	Q6PKH6	449
FOXD4L6	ZNF611	Q8N823	448
FOXD4L6	BHLHA9	Q7RTU4	446
FOXD4L6	ZNF18	P17022	431
FOXD4L6	DQX1	Q8TE96	420

IntAct

77 interactions, top by confidence:

A	B	Type	Score
FOXD4L6	MDFI	psi-mi:“MI:0915”(physical association)	0.720
MDFI	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.720
FOXD4L6	APOE	psi-mi:“MI:0915”(physical association)	0.560
ARG2	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
STEAP1B	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
ELAVL4	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L6		psi-mi:“MI:0915”(physical association)	0.560
LAMP2	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L6	PLG	psi-mi:“MI:0915”(physical association)	0.560
PSEN2	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF14	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L6	NDRG1	psi-mi:“MI:0915”(physical association)	0.560
STIP1	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
FOXD4L6	CYCS	psi-mi:“MI:0915”(physical association)	0.560
DDIT4	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
LRIF1	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
HTT	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (77): FOXD4L6 (Two-hybrid), FOXD4L6 (Two-hybrid), LRP1B (Affinity Capture-MS), DICER1 (Affinity Capture-MS), ZBTB9 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), HSPBAP1 (Affinity Capture-MS), THNSL1 (Affinity Capture-MS), ANKRD28 (Affinity Capture-MS), FBN2 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), FOXD2 (Affinity Capture-MS), GGPS1 (Affinity Capture-MS), KIAA0232 (Affinity Capture-MS), FAM192A (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

19 predictions. Top by Δscore:

Variant	Effect	Δscore
9:41128469:T:TC	acceptor_gain	0.6300
9:41128469:T:C	acceptor_gain	0.5500
9:41128466:ATGTT:A	acceptor_gain	0.4300
9:41128467:TGTTG:T	acceptor_gain	0.3600
9:41128487:C:T	acceptor_gain	0.3500
9:41128468:GTTGC:G	acceptor_gain	0.3400
9:41128466:A:AC	acceptor_gain	0.3200
9:41127749:C:CA	donor_gain	0.2800
9:41128455:GCCT:G	acceptor_gain	0.2600
9:41128459:GGGAT:G	acceptor_gain	0.2600
9:41128460:GGATG:G	acceptor_gain	0.2600
9:41128454:AGCC:A	acceptor_gain	0.2500
9:41127780:T:TA	donor_gain	0.2300
9:41128461:G:A	acceptor_gain	0.2300
9:41128342:C:CC	acceptor_gain	0.2100
9:41128465:AATGT:A	acceptor_gain	0.2100
9:41128567:T:G	acceptor_gain	0.2100
9:41128469:TTGCA:T	acceptor_gain	0.2000
9:41128566:T:TG	acceptor_gain	0.2000

AlphaMissense

2680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:41127838:C:A	W182C	1.000
9:41127838:C:G	W182C	1.000
9:41127886:G:C	F166L	1.000
9:41127886:G:T	F166L	1.000
9:41127887:A:C	F166C	1.000
9:41127887:A:G	F166S	1.000
9:41127888:A:G	F166L	1.000
9:41127793:A:C	F197L	0.999
9:41127793:A:T	F197L	0.999
9:41127795:A:G	F197L	0.999
9:41127808:G:C	F192L	0.999
9:41127808:G:T	F192L	0.999
9:41127809:A:C	F192C	0.999
9:41127810:A:G	F192L	0.999
9:41127840:A:G	W182R	0.999
9:41127840:A:T	W182R	0.999
9:41127895:G:C	N163K	0.999
9:41127895:G:T	N163K	0.999
9:41127896:T:A	N163I	0.999
9:41127905:A:T	L160H	0.999
9:41127907:G:C	N159K	0.999
9:41127907:G:T	N159K	0.999
9:41127910:G:C	H158Q	0.999
9:41127910:G:T	H158Q	0.999
9:41127912:G:C	H158D	0.999
9:41127917:A:T	I156N	0.999
9:41127928:C:A	W152C	0.999
9:41127928:C:G	W152C	0.999
9:41127930:A:G	W152R	0.999
9:41127930:A:T	W152R	0.999

dbSNP variants (sampled 300 via entrez): RS1001569234 (9:41129893 C>T), RS1006704067 (9:41127920 C>CT), RS1006735147 (9:41127076 C>G,T), RS1014182732 (9:41129598 T>C,G), RS1017466227 (9:41129902 C>A), RS1022124333 (9:41127940 C>G), RS1022181351 (9:41127094 A>G), RS1024244876 (9:41129848 C>A,G,T), RS1024321927 (9:41128769 A>G), RS1029456681 (9:41127067 C>G), RS1029486296 (9:41125945 C>T), RS1030880202 (9:41129378 A>G,T), RS1031371251 (9:41128609 C>G,T), RS1031655026 (9:41127149 C>G), RS1037712217 (9:41127742 G>T)

Disease associations

OMIM: gene `` | 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

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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