FOXD4L5

Summary

FOXD4L5 (forkhead box D4 like 5, HGNC:18522) is a protein-coding gene on chromosome 9q21.11, encoding Forkhead box protein D4-like 5 (Q5VV16).

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 653427 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 165 total
• MANE Select transcript: NM_001126334

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18522
Approved symbol	FOXD4L5
Name	forkhead box D4 like 5
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Aliases	bA15J10.2, OTTHUMG00000013332
Ensembl gene	ENSG00000204779
Ensembl biotype	protein_coding
Entrez	653427

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377420

RefSeq mRNA: 1 — MANE Select: NM_001126334 NM_001126334

CCDS: CCDS47977

Canonical transcript exons

ENST00000377420 — 1 exons

Exon	Start	End
ENSE00001681769	65282101	65285209

Expression profiles

Bgee: expression breadth broad, 72 present calls, max score 82.70.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.70	gold quality
cortical plate	UBERON:0005343	61.79	gold quality
right uterine tube	UBERON:0001302	58.63	gold quality
cerebellar hemisphere	UBERON:0002245	54.68	gold quality
cerebellum	UBERON:0002037	54.66	gold quality
cerebellar cortex	UBERON:0002129	54.63	gold quality
superior frontal gyrus	UBERON:0002661	54.54	gold quality
right hemisphere of cerebellum	UBERON:0014890	53.20	gold quality
stromal cell of endometrium	CL:0002255	50.99	silver quality
granulocyte	CL:0000094	50.94	silver quality
Ammon’s horn	UBERON:0001954	50.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	50.60	gold quality
prefrontal cortex	UBERON:0000451	50.37	gold quality
cerebral cortex	UBERON:0000956	49.99	gold quality
frontal cortex	UBERON:0001870	49.99	gold quality
nucleus accumbens	UBERON:0001882	49.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	49.88	gold quality
anterior cingulate cortex	UBERON:0009835	49.43	gold quality
lower esophagus mucosa	UBERON:0035834	49.28	gold quality
right frontal lobe	UBERON:0002810	49.16	gold quality
putamen	UBERON:0001874	48.63	gold quality
ganglionic eminence	UBERON:0004023	48.61	silver quality
brain	UBERON:0000955	48.57	gold quality
caudate nucleus	UBERON:0001873	48.39	gold quality
primary visual cortex	UBERON:0002436	47.96	gold quality
hypothalamus	UBERON:0001898	46.47	gold quality
tonsil	UBERON:0002372	46.24	gold quality
endometrium	UBERON:0001295	46.23	silver quality
colonic epithelium	UBERON:0000397	45.59	gold quality
amygdala	UBERON:0001876	44.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting FOXD4L5, 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-3924	100.00	72.09	2394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-31-5P	98.58	68.35	1239

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), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein D4-like 5 — Q5VV16 (reviewed: Q5VV16)

All UniProt accessions (1): Q5VV16

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001119806* (*=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-Q5VV16-F1	57.03	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): chr9q21, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR95_5P, MIR4753_3P, MIR130A_5P, MIR7154_5P, MIR6818_3P, MIR31_5P, MIR1206, MIR877_5P, MIR3152_3P, MIR4761_5P, MIR1266_3P, MANNO_MIDBRAIN_NEUROTYPES_HGABA

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 (5): 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), 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
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXD4L5	ANKRD20A2P	Q5SQ80	652
FOXD4L5	ZNF595	Q8IYB9	508
FOXD4L5	POU5F2	Q8N7G0	390
FOXD4L5	MYO18B	Q8IUG5	378
FOXD4L5	ARHGEF5	Q12774	375
FOXD4L5	NKX1-1	Q15270	375
FOXD4L5	NKX1-2	Q9UD57	339
FOXD4L5	MUC12	Q9UKN1	328
FOXD4L5	NKX2-4	Q9H2Z4	322
FOXD4L5	NKX2-6	A6NCS4	320
FOXD4L5	NKX6-3	A6NJ46	290
FOXD4L5	FOXR2	Q6PJQ5	277
FOXD4L5	NKX2-8	O15522	267
FOXD4L5	POU6F2	P78424	265
FOXD4L5	SOX14	O95416	263
FOXD4L5	POU6F1	Q14863	263

IntAct

0 interactions, top by confidence:

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	159
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

45 predictions. Top by Δscore:

Variant	Effect	Δscore
9:65284460:ATGTT:A	acceptor_gain	0.5300
9:65284463:CAACA:C	acceptor_gain	0.5100
9:65284481:C:T	acceptor_gain	0.4600
9:65284461:TGTTG:T	acceptor_gain	0.4500
9:65284462:GTTGC:G	acceptor_gain	0.4500
9:65284462:A:AG	acceptor_gain	0.4400
9:65284479:TGC:T	acceptor_gain	0.4200
9:65284463:T:TC	acceptor_gain	0.4000
9:65284464:GCAAC:G	acceptor_gain	0.4000
9:65284465:TGCAA:T	acceptor_gain	0.4000
9:65285142:A:C	donor_gain	0.3700
9:65284461:A:G	acceptor_gain	0.3500
9:65285132:C:CA	donor_gain	0.3500
9:65285140:T:G	donor_gain	0.3500
9:65284479:G:A	acceptor_gain	0.3400
9:65285131:G:GT	donor_gain	0.3400
9:65284463:T:C	acceptor_gain	0.3300
9:65284453:GGGAT:G	acceptor_gain	0.3000
9:65284454:GGATG:G	acceptor_gain	0.3000
9:65284456:CATCC:C	acceptor_gain	0.2900
9:65284457:TCATC:T	acceptor_gain	0.2900
9:65284463:TTGC:T	acceptor_gain	0.2900
9:65284815:C:T	acceptor_gain	0.2900
9:65284813:G:A	acceptor_gain	0.2800
9:65285018:C:A	donor_gain	0.2800
9:65284462:AACA:A	acceptor_gain	0.2700
9:65284455:G:A	acceptor_gain	0.2600
9:65282246:C:CG	acceptor_gain	0.2500
9:65282291:T:TA	acceptor_gain	0.2400
9:65284455:ATCC:A	acceptor_gain	0.2400

AlphaMissense

2674 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:65283832:C:A	W182C	1.000
9:65283832:C:G	W182C	1.000
9:65283880:G:C	F166L	1.000
9:65283880:G:T	F166L	1.000
9:65283881:A:C	F166C	1.000
9:65283882:A:G	F166L	1.000
9:65283787:A:C	F197L	0.999
9:65283787:A:T	F197L	0.999
9:65283789:A:G	F197L	0.999
9:65283802:G:C	F192L	0.999
9:65283802:G:T	F192L	0.999
9:65283803:A:C	F192C	0.999
9:65283804:A:G	F192L	0.999
9:65283834:A:G	W182R	0.999
9:65283834:A:T	W182R	0.999
9:65283881:A:G	F166S	0.999
9:65283890:T:A	N163I	0.999
9:65283906:G:C	H158D	0.999
9:65283911:A:T	I156N	0.999
9:65283922:C:A	W152C	0.999
9:65283922:C:G	W152C	0.999
9:65283924:A:G	W152R	0.999
9:65283924:A:T	W152R	0.999
9:65283952:G:C	F142L	0.999
9:65283952:G:T	F142L	0.999
9:65283954:A:G	F142L	0.999
9:65283967:G:C	F137L	0.999
9:65283967:G:T	F137L	0.999
9:65283969:A:G	F137L	0.999
9:65283803:A:G	F192S	0.998

dbSNP variants (sampled 300 via entrez): RS1000503011 (9:65286323 C>A,G), RS1001041499 (9:65285106 T>A), RS1001751773 (9:65283436 C>A,G), RS1002076765 (9:65282495 A>G), RS1007930470 (9:65284803 C>A,T), RS1009391852 (9:65286465 T>C), RS1017190138 (9:65282663 C>G,T), RS1017515371 (9:65283487 C>A,T), RS1018075710 (9:65283814 G>A), RS1018344940 (9:65284854 C>T), RS1024321638 (9:65282205 GT>G), RS1024753220 (9:65286498 C>T), RS1025293912 (9:65282805 C>A,T), RS1025870625 (9:65283557 G>A,C,T), RS1032062181 (9:65285150 G>A)

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

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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