FOXJ1

Summary

FOXJ1 (forkhead box J1, HGNC:3816) is a protein-coding gene on chromosome 17q25.1, encoding Forkhead box protein J1 (Q92949). Transcription factor specifically required for the formation of motile cilia.

This gene encodes a member of the forkhead family of transcription factors. Similar genes in zebrafish and mouse have been shown to regulate the transcription of genes that control the production of motile cilia. The mouse ortholog also functions in the determination of left-right asymmetry. Polymorphisms in this gene are associated with systemic lupus erythematosus and allergic rhinitis.

Source: NCBI Gene 2302 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliary dyskinesia, primary, 43 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 126 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 52
• Transcription factor: yes — 21 downstream targets (CollecTRI)
• MANE Select transcript: NM_001454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3816
Approved symbol	FOXJ1
Name	forkhead box J1
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	HFH-4, HFH4
Ensembl gene	ENSG00000129654
Ensembl biotype	protein_coding
OMIM	602291
Entrez	2302

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000322957, ENST00000861552, ENST00000861553

RefSeq mRNA: 1 — MANE Select: NM_001454 NM_001454

CCDS: CCDS32739

Canonical transcript exons

ENST00000322957 — 3 exons

Exon	Start	End
ENSE00000890526	76139898	76140564
ENSE00001283858	76136333	76138120
ENSE00001434544	76141114	76141245

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 99.20.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9787 / max 208.5999, expressed in 430 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168175	1.7337	354
168173	0.7844	221
168171	0.2375	108
168172	0.1232	67
168174	0.0566	32
168177	0.0233	5
168176	0.0198	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.20	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.16	gold quality
epithelium of bronchus	UBERON:0002031	95.38	gold quality
bronchial epithelial cell	CL:0002328	95.03	gold quality
bronchus	UBERON:0002185	95.01	gold quality
nasal cavity epithelium	UBERON:0005384	90.14	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.80	silver quality
tongue squamous epithelium	UBERON:0006919	83.97	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.73	silver quality
ventricular zone	UBERON:0003053	83.36	gold quality
vena cava	UBERON:0004087	82.99	silver quality
epithelium of nasopharynx	UBERON:0001951	82.00	silver quality
trachea	UBERON:0003126	81.08	gold quality
choroid plexus epithelium	UBERON:0003911	81.02	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	80.46	gold quality
caput epididymis	UBERON:0004358	80.09	gold quality
left testis	UBERON:0004533	79.95	gold quality
nasal cavity mucosa	UBERON:0001826	79.17	gold quality
gluteal muscle	UBERON:0002000	79.06	gold quality
right testis	UBERON:0004534	79.00	gold quality
parotid gland	UBERON:0001831	78.74	gold quality
right lung	UBERON:0002167	77.72	gold quality
sperm	CL:0000019	77.65	silver quality
inferior olivary complex	UBERON:0002127	77.47	silver quality
male germ cell	CL:0000015	77.40	silver quality
testis	UBERON:0000473	77.40	gold quality
type B pancreatic cell	CL:0000169	77.39	silver quality
fallopian tube	UBERON:0003889	76.79	gold quality
body of tongue	UBERON:0011876	76.77	silver quality
superior vestibular nucleus	UBERON:0007227	76.38	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	1264.60
E-MTAB-8221	yes	878.93
E-CURD-114	yes	567.77
E-HCAD-1	yes	28.61
E-MTAB-10287	yes	27.63
E-ANND-3	yes	8.13

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

21 targets.

Target	Regulation
AMELX	Unknown
ASPM	Unknown
CEL
CETN2	Activation
CFTR
DLX2	Activation
DNAH11	Activation
DNAI1	Activation
DNALI1	Activation
EFHC1	Activation
EZR	Activation
FOXA1	Activation
FOXJ1	Unknown
IGF2
SCGB1A1	Activation
SERPINA3
SLC9A3R1	Activation
SPAG6	Activation
TEKT1	Activation
TEKT2	Activation
TUBA1A	Activation

Upstream regulators (CollecTRI, top): DLX2, FOXJ1, LEF1, MYB, PITX2, SOX2

miRNA regulators (miRDB)

62 targeting FOXJ1, 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-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-7154-5P	99.69	70.52	1900

Literature-anchored findings (GeneRIF, showing 21)

• Single nucleotide polymorphisms were identified in FOXJ1 and a significant association was found with allergic rhinitis. (PMID:16518568)
• goblet cells formed in response to IL-13 treatment are in part or wholly derived from progenitors that express the ciliated cell marker, FOXJ1 (PMID:20539013)
• FOXJ1 was overexpressed in HCCs and associated with histological grade and poor prognosis. (PMID:22488567)
• Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. (PMID:22945654)
• Rer1p depletion reduced ciliary length and function by increasing gamma-secretase complex assembly and activity and, consequently, enhancing Notch signaling as well as reducing Foxj1a expression. (PMID:23479743)
• FOXJ1 is an important regulator of cilia gene expression during ciliated cell differentiation, with RFX3 as a transcriptional co-activator to FOXJ1. (PMID:23822649)
• Decreased FOXJ1 expression was correlated with clinic stage, lymph node metastasis, and distant metastasis, and lower FOXJ1 expression independently predicted shorter survival time in gastric carcinoma. (PMID:24809300)
• By stimulating ciliogenesis with the transcription factor FOXJ1, it may be possible to maintain close to normal cilia length despite the stress of cigarette smoking. (PMID:24828273)
• Both protein and mRNA levels of ciliogenesis-associated markers CP110, Foxj1, TAp73 were significantly increased in patients with nasal polyps versus those seen in control subjects and were positively correlated with cilia length (PMID:25201258)
• In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome (PMID:26690880)
• Findings demonstrate that increased FOXJ1 contributes to the progression of CRC, which might be associated with the promotion effect of b-catenin nuclear translocation. (PMID:28209947)
• TIM-3 and FOXJ1 exhibited abnormally high expression levels in prostate cancer. (PMID:28952222)
• Our findings provide clues regarding the role of FOXJ1 as a tumor inducer in bladder cancer and an enhancer in glycolysis. Targeting FOXJ1 could be a potential therapeutic strategy in bladder cancer. (PMID:29129693)
• Downregulation and aberrant localization of FOXJ1 may be crucial characteristics of the allergic nasal mucosa. (PMID:29635245)
• Knockdown of FOXJ1 inhibits the proliferation, migration, invasion, and glycolysis in laryngeal squamous cell carcinoma cells. (PMID:31062413)
• Heterozygous de novo mutations in FOXJ1. (PMID:31630787)
• Androglobin gene expression patterns and FOXJ1-dependent regulation indicate its functional association with ciliogenesis. (PMID:33453283)
• Autosomal dominant variants in FOXJ1 causing primary ciliary dyskinesia in two patients with obstructive hydrocephalus. (PMID:34132502)
• Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study. (PMID:36323878)
• Down-expression of Foxj1 on airway epithelium with impaired cilia architecture in non-cystic fibrosis bronchiectasis implies disease severity. (PMID:36929635)
• Congenital heart defects caused by FOXJ1. (PMID:37158461)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxj1a	ENSDARG00000101919
mus_musculus	Foxj1	ENSMUSG00000034227
rattus_norvegicus	AABR07030823.1	ENSRNOG00000046001

Paralogs (41): FOXP3 (ENSG00000049768), FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXM1 (ENSG00000111206), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), 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), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein J1 — Q92949 (reviewed: Q92949)

Alternative names: Forkhead-related protein FKHL13, Hepatocyte nuclear factor 3 forkhead homolog 4

All UniProt accessions (1): Q92949

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor specifically required for the formation of motile cilia. Acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157. Binds the DNA consensus sequences 5’-HWDTGTTTGTTTA-3’ or 5’-KTTTGTTGTTKTW-3’ (where H is not G, W is A or T, D is not C, and K is G or T). Activates the transcription of a variety of ciliary proteins in the developing brain and lung.

Subcellular location. Nucleus.

Tissue specificity. Testis, oviduct, lung and brain cortex.

Disease relevance. Allergic rhinitis (ALRH) [MIM:607154] A common disease with complex inheritance characterized by mucosal inflammation caused by allergen exposure. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Ciliary dyskinesia, primary, 43 (CILD43) [MIM:618699] A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients with this disorder also develop significant obstructive hydrocephalus. Other more variable features include infertility and about a 50% chance of situs inversus or other left-right asymmetry defects. CILD43 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the FOXJ1 family.

RefSeq proteins (1): NP_001445* (*=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
IPR047512	FH_FOXJ1	Domain
IPR047513	FOXJ1	Family

Pfam: PF00250

UniProt features (18 total): sequence conflict 8, region of interest 3, compositionally biased region 3, sequence variant 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92949-F1	59.44	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 353 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_TOLERANCE_INDUCTION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_METANEPHROS_DEVELOPMENT, GOBP_B_CELL_ACTIVATION, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (37): negative regulation of transcription by RNA polymerase II (GO:0000122), central tolerance induction (GO:0002508), negative regulation of germinal center formation (GO:0002635), positive regulation of central B cell tolerance induction (GO:0002897), negative regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002924), regulation of transcription by RNA polymerase II (GO:0006357), humoral immune response (GO:0006959), spermatogenesis (GO:0007283), determination of left/right symmetry (GO:0007368), pattern specification process (GO:0007389), brain development (GO:0007420), heart development (GO:0007507), intracellular protein localization (GO:0008104), actin cytoskeleton organization (GO:0030036), ciliary basal body organization (GO:0032053), negative regulation of interleukin-6 production (GO:0032715), negative regulation of T cell differentiation in thymus (GO:0033085), axoneme assembly (GO:0035082), establishment of apical/basal cell polarity (GO:0035089), metanephric part of ureteric bud development (GO:0035502), negative regulation of T cell proliferation (GO:0042130), motile cilium assembly (GO:0044458), positive regulation of transcription by RNA polymerase II (GO:0045944), cell maturation (GO:0048469), negative regulation of B cell activation (GO:0050869), leukocyte migration (GO:0050900), cilium assembly (GO:0060271), lung epithelium development (GO:0060428), epithelium development (GO:0060429), glomerular parietal epithelial cell development (GO:0072016), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), positive regulation of lung ciliated cell differentiation (GO:1901248), regulation of DNA-templated transcription (GO:0006355), cell projection organization (GO:0030030), regulation of epithelial cell differentiation (GO:0030856), positive regulation of DNA-templated transcription (GO:0045893), left/right pattern formation (GO:0060972)

GO Molecular Function (8): transcription cis-regulatory region binding (GO:0000976), 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 transcription activator activity, RNA polymerase II-specific (GO:0001228), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
animal organ development	2
negative regulation of DNA-templated transcription	1
tolerance induction	1
germinal center formation	1
regulation of germinal center formation	1
negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
negative regulation of developmental process	1
central B cell tolerance induction	1
positive regulation of central tolerance induction	1
positive regulation of B cell tolerance induction	1
regulation of central B cell tolerance induction	1
humoral immune response mediated by circulating immunoglobulin	1
negative regulation of immunoglobulin mediated immune response	1
negative regulation of humoral immune response	1
regulation of humoral immune response mediated by circulating immunoglobulin	1
immune response	1
developmental process involved in reproduction	1
male gamete generation	1
determination of bilateral symmetry	1
left/right pattern formation	1
multicellular organism development	1
multicellular organismal process	1
central nervous system development	1
head development	1
circulatory system development	1
macromolecule localization	1
cytoskeleton organization	1
actin filament-based process	1
microtubule organizing center organization	1
cilium organization	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
T cell differentiation in thymus	1
regulation of T cell differentiation in thymus	1
negative regulation of T cell differentiation	1

Protein interactions and networks

STRING

2012 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXJ1	RFX2	P48378	867
FOXJ1	MCIDAS	D6RGH6	803
FOXJ1	SCGB1A1	P11684	791
FOXJ1	SFTPC	P11686	770
FOXJ1	IFT88	Q13099	769
FOXJ1	SCGB3A2	Q96PL1	763
FOXJ1	GMNC	A6NCL1	687
FOXJ1	PITX2	Q99697	680
FOXJ1	MUC5AC	P98088	676
FOXJ1	RFX3	P48380	671
FOXJ1	KRT5	P13647	659
FOXJ1	CCNO	P22674	633
FOXJ1	DNAH5	Q8TE73	625
FOXJ1	SHH	Q15465	623
FOXJ1	MUC5B	Q9HC84	622

IntAct

25 interactions, top by confidence:

A	B	Type	Score
RFX2	FOXJ1	psi-mi:“MI:0915”(physical association)	0.800
FOXJ1	RFX1	psi-mi:“MI:0914”(association)	0.730
FOXJ1	RFX3	psi-mi:“MI:0914”(association)	0.730
FOXJ1	PEX14	psi-mi:“MI:0914”(association)	0.530
FOXJ1	GRB2	psi-mi:“MI:0915”(physical association)	0.400
THRA	FOXJ1	psi-mi:“MI:0915”(physical association)	0.370
OIP5	FOXJ1	psi-mi:“MI:0915”(physical association)	0.370
FOXJ1	TWF2	psi-mi:“MI:0915”(physical association)	0.370
TRMT6	FOXJ1	psi-mi:“MI:0915”(physical association)	0.370
FOXJ1	NMRAL1	psi-mi:“MI:0915”(physical association)	0.370
FOXJ1	SLC37A3	psi-mi:“MI:0915”(physical association)	0.370
RPUSD1	FOXJ1	psi-mi:“MI:0915”(physical association)	0.370
FOXJ1	ACSL4	psi-mi:“MI:0914”(association)	0.350
FOXJ3	RPA2	psi-mi:“MI:0914”(association)	0.350
FOXJ1	PEX14	psi-mi:“MI:0914”(association)	0.350
RFX3	FOXJ1	psi-mi:“MI:0915”(physical association)	0.000
PLK1	FOXJ1	psi-mi:“MI:0915”(physical association)	0.000
HDAC1	FOXJ1	psi-mi:“MI:0915”(physical association)	0.000
XYLT2	FOXJ1	psi-mi:“MI:0915”(physical association)	0.000
CFAP20	FOXJ1	psi-mi:“MI:0915”(physical association)	0.000
RFX2	FOXJ1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (42): RFX1 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), CFAP20 (Affinity Capture-MS), RFX3 (Affinity Capture-MS), RFX2 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), FOXJ1 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX3 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), RFX2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUS0, A0A5F9ZHS7, A7E346, A7MB34, A8MZG2, B2RU40, D4A9R4, O08574, O75593, P0C1Z6, P0CG20, Q0VG99, Q0ZCJ7, Q17QH7, Q29RM2, Q2KIS6, Q2M2S6, Q2M3G4, Q2NL68, Q32LE6, Q3U1J1, Q5JXC2, Q5R815, Q5SW24, Q61660, Q63247, Q6NZ36, Q6PBC9, Q6ZN01, Q6ZRI6, Q7TN08, Q7Z591, Q80VF6, Q86WR7, Q8BG26, Q8BP99, Q8BXQ8, Q8IYS4, Q8N9Y4, Q8NAV2

Diamond homologs: A4IFD2, F1QDF8, F1R8Z9, O00409, O13606, O15409, O42097, P0CF24, P23512, P32314, P32315, P33205, P33206, P35582, P35583, P55316, P55317, P56260, P58462, P58463, P84961, Q00939, Q01167, Q07342, Q16676, Q17381, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q28D67, Q28EM1, Q28G71, Q28HT3, Q2LE08, Q32NH9, Q33BP8, Q3BJS3

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
RFX3	“up-regulates activity”	FOXJ1	binding
FOXJ1	“up-regulates quantity by expression”	CETN2	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	DNAH11	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	DNAI1	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	DNALI1	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	EFHC1	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	SPAG6	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	TEKT1	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	TEKT2	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	TUBA1A	“transcriptional regulation”
FOXJ1	“up-regulates quantity by expression”	Axonemal_Dynein	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	91
Likely benign	17
Benign	4

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1327681	NM_001454.4(FOXJ1):c.837del (p.Lys280fs)	Pathogenic
2578017	GRCh37/hg19 17q25.1(chr17:72718277-74142256)	Pathogenic
800278	NM_001454.4(FOXJ1):c.901G>T (p.Glu301Ter)	Pathogenic
800279	NM_001454.4(FOXJ1):c.868_871dup (p.Thr291fs)	Pathogenic
800280	NM_001454.4(FOXJ1):c.826C>T (p.Gln276Ter)	Pathogenic
800281	NM_001454.4(FOXJ1):c.967del (p.Glu323fs)	Pathogenic
2631063	NM_001454.4(FOXJ1):c.832del (p.Leu278fs)	Likely pathogenic
3066105	NM_001454.4(FOXJ1):c.913dup (p.Leu305fs)	Likely pathogenic
3390985	NM_001454.4(FOXJ1):c.223dup (p.Leu75fs)	Likely pathogenic

SpliceAI

306 predictions. Top by Δscore:

Variant	Effect	Δscore
17:76138116:GAATT:G	acceptor_gain	1.0000
17:76138118:ATT:A	acceptor_gain	1.0000
17:76138119:TT:T	acceptor_gain	1.0000
17:76138120:TCT:T	acceptor_loss	1.0000
17:76138121:C:CC	acceptor_gain	1.0000
17:76138122:T:A	acceptor_loss	1.0000
17:76138125:G:C	acceptor_gain	1.0000
17:76138125:G:GC	acceptor_gain	1.0000
17:76138128:C:CT	acceptor_gain	1.0000
17:76138129:A:T	acceptor_gain	1.0000
17:76138140:A:T	acceptor_gain	1.0000
17:76138117:AATT:A	acceptor_gain	0.9900
17:76138139:C:CT	acceptor_gain	0.9900
17:76139890:T:TA	donor_gain	0.9900
17:76139892:CTCTA:C	donor_loss	0.9900
17:76139893:TCTA:T	donor_loss	0.9900
17:76139894:CTACC:C	donor_loss	0.9900
17:76139895:TACCT:T	donor_loss	0.9900
17:76139896:A:T	donor_loss	0.9900
17:76139900:G:A	donor_gain	0.9900
17:76141108:CCTTA:C	donor_loss	0.9900
17:76141109:CTTA:C	donor_loss	0.9900
17:76141110:TTACC:T	donor_loss	0.9900
17:76141111:TA:T	donor_loss	0.9900
17:76139898:C:G	donor_loss	0.9800
17:76141113:CCTGG:C	donor_gain	0.9800
17:76138089:T:C	acceptor_gain	0.9700
17:76139440:AGAG:A	donor_gain	0.9700
17:76139887:G:A	donor_gain	0.9700
17:76140744:T:A	donor_gain	0.9500

AlphaMissense

2708 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:76138032:C:G	R196P	1.000
17:76138034:C:A	W195C	1.000
17:76138034:C:G	W195C	1.000
17:76138035:C:G	W195S	1.000
17:76138036:A:C	W195G	1.000
17:76138036:A:G	W195R	1.000
17:76138036:A:T	W195R	1.000
17:76138037:G:C	F194L	1.000
17:76138037:G:T	F194L	1.000
17:76138038:A:C	F194C	1.000
17:76138038:A:G	F194S	1.000
17:76138039:A:C	F194V	1.000
17:76138039:A:G	F194L	1.000
17:76138039:A:T	F194I	1.000
17:76138041:C:T	G193D	1.000
17:76138042:C:G	G193R	1.000
17:76138044:C:A	G192V	1.000
17:76138044:C:T	G192E	1.000
17:76138045:C:A	G192W	1.000
17:76138045:C:G	G192R	1.000
17:76138045:C:T	G192R	1.000
17:76138046:C:A	K191N	1.000
17:76138046:C:G	K191N	1.000
17:76138047:T:A	K191M	1.000
17:76138047:T:G	K191T	1.000
17:76138048:T:C	K191E	1.000
17:76138048:T:G	K191Q	1.000
17:76138050:C:A	G190V	1.000
17:76138050:C:T	G190D	1.000
17:76138051:C:A	G190C	1.000

dbSNP variants (sampled 300 via entrez): RS1001034644 (17:76139201 G>C), RS1001973705 (17:76139273 G>C), RS1002499625 (17:76138437 G>A,T), RS1002573079 (17:76138265 A>C,G), RS1002712683 (17:76143011 G>C,T), RS1002848635 (17:76142787 G>A,C), RS1003172519 (17:76141616 G>A), RS1003481587 (17:76137019 A>T), RS1003576472 (17:76137330 G>C,T), RS1003823237 (17:76142530 T>C), RS1003862659 (17:76136981 C>A,T), RS1004028897 (17:76137944 G>A), RS1004157366 (17:76142208 A>G), RS1004935919 (17:76136674 C>T), RS1005031337 (17:76136942 ACT>A)

Disease associations

OMIM: gene MIM:602291 | disease phenotypes: MIM:618699, MIM:609757

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 43	Strong	Autosomal dominant
primary ciliary dyskinesia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 43	Definitive	AD

Mondo (3): ciliary dyskinesia, primary, 43 (MONDO:0032874), 7q11.23 microduplication syndrome (MONDO:0012342), primary ciliary dyskinesia (MONDO:0016575)

Orphanet (1): 7q11.23 microduplication syndrome (Orphanet:96121)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001627	Abnormal heart morphology
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001742	Nasal congestion
HP:0001746	Asplenia
HP:0001748	Polysplenia
HP:0002011	Morphological central nervous system abnormality
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0003363	Abdominal situs inversus
HP:0005301	Persistent left superior vena cava

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
C565723	Williams-Beuren Region Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	4
Silicon Dioxide	decreases expression, decreases reaction, increases expression	3
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases expression	2
Genistein	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ormosil	affects binding, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Microplastics	decreases expression, increases abundance	1
Air Pollutants	increases abundance, increases expression	1
Ascorbic Acid	affects cotreatment, increases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Cadmium	increases expression	1
Carmustine	decreases expression	1
Copper	affects binding, decreases expression	1
Diethylnitrosamine	decreases expression	1
Diethylstilbestrol	decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	affects response to substance	1
Fonofos	increases methylation	1
Estradiol	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_A2A6	SEES3-1V human FOXJ1, clone1	Embryonic stem cell	Male
CVCL_A2A7	SEES3-1V human FOXJ1, clone2	Embryonic stem cell	Male
CVCL_A2A8	SEES3-1V human FOXJ1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT04901715	EARLY_PHASE1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia
NCT01929356	Not specified	RECRUITING	Chest Physiotherapy and Lung Function in Primary Ciliary Dyskinesia
NCT02389049	Not specified	COMPLETED	Genetics of Primary Ciliary Dyskinesia
NCT02419365	Not specified	RECRUITING	International Primary Ciliary Dyskinesia (PCD) Registry
NCT02699177	Not specified	UNKNOWN	In Vivo Measurements of Nasal Ciliary Beat Frequency by Using Interferometry
NCT02704455	Not specified	NOT_YET_RECRUITING	Registry Study on Primary Ciliary Dyskinesia in Chinese Children
NCT03271840	Not specified	COMPLETED	Registry for Primary Ciliary Dyskinesia
NCT03279965	Not specified	UNKNOWN	MRI in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03320382	Not specified	UNKNOWN	Multiple Breath Washout, a Clinimetric Dataset
NCT03370029	Not specified	COMPLETED	Respiratory Muscle Strength, Exercise Capacity and Physical Activity Levels in Children Primary Ciliary Dyskinesia
NCT03494894	Not specified	COMPLETED	Bacteriological Link Between Upper and Lower Airways in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03517865	Not specified	ACTIVE_NOT_RECRUITING	International Primary Ciliary Dyskinesia Cohort
NCT03606200	Not specified	RECRUITING	Swiss Primary Ciliary Dyskinesia Registry
NCT03704207	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT03704896	Not specified	UNKNOWN	PRospective Observational Multicentre Study on VAriability of Lung Function in Stable PCD Patients
NCT03801395	Not specified	COMPLETED	PCD New Gene Discovery
NCT03809091	Not specified	UNKNOWN	WGS of Korean Idiopathic Bronchiectasis
NCT03832491	Not specified	COMPLETED	Effect of Game Based Approach on Oxygenation, Functional Capacity and Quality of Life in Primary Ciliary Dyskinesia
NCT04161313	Not specified	COMPLETED	Respiratory Function, Exercise Capacity and Peripheral Muscle Strength Among Patients With CF, PCD and Healthy Children
NCT04476433	Not specified	COMPLETED	Intervention in Chronic Pediatric Patients and Their Families.
NCT04489472	Not specified	UNKNOWN	The Effect of a Dietary Supplement Rich in Nitric Oxide in Patients Diagnosed With Primary Ciliary Dyskinesia.
NCT04602481	Not specified	RECRUITING	Living With Primary Ciliary Dyskinesia (Living With PCD)