FOXD1

Summary

FOXD1 (forkhead box D1, HGNC:3802) is a protein-coding gene on chromosome 5q13.2, encoding Forkhead box protein D1 (Q16676). Transcription factor involved in regulation of gene expression in a variety of processes, including formation of positional identity in the developing retina, regionalization of the optic chiasm, morphogenesis of the kidney, and neuralization of ectodermal cells.

This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. Studies of the orthologous mouse protein indicate that it functions in kidney development by promoting nephron progenitor differentiation, and it also functions in the development of the retina and optic chiasm. It may also regulate inflammatory reactions and prevent autoimmunity.

Source: NCBI Gene 2297 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_004472

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3802
Approved symbol	FOXD1
Name	forkhead box D1
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FREAC4
Ensembl gene	ENSG00000251493
Ensembl biotype	protein_coding
OMIM	601091
Entrez	2297

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000513595, ENST00000615637

RefSeq mRNA: 1 — MANE Select: NM_004472 NM_004472

CCDS: CCDS75259

Canonical transcript exons

ENST00000615637 — 1 exons

Exon	Start	End
ENSE00003742832	73446266	73448777

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 93.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6258 / max 303.4763, expressed in 1297 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62057	12.0856	1230
62055	2.2900	839
62053	1.0696	576
62056	1.0048	577
62054	0.1758	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	93.12	gold quality
sural nerve	UBERON:0015488	90.86	gold quality
trigeminal ganglion	UBERON:0001675	90.32	gold quality
dorsal root ganglion	UBERON:0000044	88.53	gold quality
cartilage tissue	UBERON:0002418	88.53	gold quality
tibial nerve	UBERON:0001323	87.92	gold quality
pigmented layer of retina	UBERON:0001782	85.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.51	gold quality
stromal cell of endometrium	CL:0002255	80.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	73.60	gold quality
lower esophagus	UBERON:0013473	73.56	gold quality
metanephros	UBERON:0000081	73.08	gold quality
renal glomerulus	UBERON:0000074	71.49	gold quality
metanephric glomerulus	UBERON:0004736	71.22	gold quality
endometrium epithelium	UBERON:0004811	70.36	silver quality
lower esophagus mucosa	UBERON:0035834	70.12	gold quality
descending thoracic aorta	UBERON:0002345	68.86	gold quality
cortex of kidney	UBERON:0001225	67.55	gold quality
choroid plexus epithelium	UBERON:0003911	67.54	silver quality
cranial nerve II	UBERON:0000941	66.73	gold quality
embryo	UBERON:0000922	65.60	gold quality
metanephros cortex	UBERON:0010533	65.11	gold quality
kidney epithelium	UBERON:0004819	64.49	silver quality
esophagus	UBERON:0001043	64.26	gold quality
hypothalamus	UBERON:0001898	63.62	gold quality
left testis	UBERON:0004533	62.96	gold quality
testis	UBERON:0000473	62.71	gold quality
medial globus pallidus	UBERON:0002477	62.19	silver quality
right testis	UBERON:0004534	61.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.45

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
DCN
EFNA5	Repression
FOXG1	Repression
PGF	Activation
PRKAR1A	Activation
SERPINE1	Activation

JASPAR motifs

Motif	Name	Family
MA0031.1	FOXD1	FOX
MA0031.2	FOXD1	FOX

JASPAR matrix evidence (PMIDs): PMID:7957066

Upstream regulators (CollecTRI, top): ETS1, FOXG1, GLI1, SMAD6

miRNA regulators (miRDB)

44 targeting FOXD1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-4251	99.40	69.19	3363

Literature-anchored findings (GeneRIF, showing 36)

• the level of Smad6s can alter the level of TGF-beta and the subsequent induction of PAI-1 via a FoxD1 transcription site (PMID:15716278)
• In this review, we focus on the role of four specific FOX factors (FOXD1, FOXL2, FOXO1 and FOXP3) in gonadotropin hormone production (PMID:24099863)
• FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27 (PMID:25462566)
• Lung cancer patients with high FOXD1 expression survive for a significantly shorter time than those with low FOXD1 expression. (PMID:25550559)
• our findings define a FOXD1-ALDH1A3 pathway in controling the clonogenic and tumorigenic potential of mesenchymal glioma stem-like cells in glioblastoma tumors (PMID:27569208)
• Results showed that FOXD1 is a major actor in mammalian reproduction as sequence variants generated recurrent spontaneous abortion (RSA) and embryonic resorption (ER). Data propose that the FOXD1-p.429AlaAla mutation might be used as an RSA molecular marker while FOXD1 p.Ala88Gly variant might have a protective effect. (PMID:27805902)
• The role of FOXD1 in glioma tumorigenesis, migration and progression.High FOXD1 expression in glioma. (PMID:28075458)
• FOXD1 promoted the expression of Plk2 mRNA and protein in colorectal cancer cells. (PMID:29864920)
• FOXD1 is overexpressed in osteosarcoma while MiR-30a-5p is lowexpressed. MiR-30a-5p directly regulates FOXD1 by binding its 3’-UTR. (PMID:29936179)
• FOXD1 may influence invasion and migration via indirect regulation of MMP9 and RAC1B alternative splicing in melanoma cells. (PMID:30110134)
• FOXD1-dependent MICU1 expression regulates mitochondrial activity and cell differentiation (PMID:30158529)
• as well as stemness abilities but stronger senescence and higher apoptosis rate. CONCLUSION: We found that overexpression of miR-338-5p suppresses glioma cell proliferation, migration, and invasion and accelerates its senescence and apoptosis by decreasing FOXD1 expression via inhibition of activation of MAPK-signaling pathway. (PMID:30225541)
• Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in non-small cell lung cancer cells. (PMID:30562753)
• Suppression of miR-92a-1-5p and restoration of FOXD1 may be a preventive approach for gastric IM in patients with bile regurgitation. (PMID:30635407)
• YAP cooperated with TEA domain transcriptional factor (TEAD) to activate the expression of forkhead box D1 (FOXD1), a geroprotective protein. YAP deficiency led to the down-regulation of FOXD1. (PMID:30933975)
• long noncoding RNA POU3 F3, induced by transcription factor SP1, acts as an oncogene in the cervical cancer tumorigenesis via regulating miR-127-5p/FOXD1 axis. (PMID:31252264)
• Investigated forkhead box D1 (FOXD1) gene mutations in patients affected by repeated implantation failure (RIF), intra-uterine growth restriction(IUGR), and preeclampsia )PE) by direct sequencing and bioinformatics analysis. Results argue in favour of FOXD1 mutations’ central role in recurrent pregnancy loss (RPL), RIF, IUGR and PE. (PMID:31395028)
• miR-30a inhibits androgen-independent growth of prostate cancer via targeting MYBL2, FOXD1, and SOX4. (PMID:32294305)
• FOXD1-AS1 regulates FOXD1 translation and promotes gastric cancer progression and chemoresistance by activating the PI3K/AKT/mTOR pathway. (PMID:32460412)
• FOXD1, negatively regulated by miR-186, promotes the proliferation, metastasis and radioresistance of nasopharyngeal carcinoma cells. (PMID:32568181)
• Forkhead box D1 promotes EMT and chemoresistance by upregulating lncRNA CYTOR in oral squamous cell carcinoma. (PMID:33352248)
• FOXD1 regulates cell division in clear cell renal cell carcinoma. (PMID:33761914)
• FOXD1 promotes dedifferentiation and targeted therapy resistance in melanoma by regulating the expression of connective tissue growth factor. (PMID:33837564)
• FOXD1 is a prognostic biomarker and correlated with macrophages infiltration in head and neck squamous cell carcinoma. (PMID:34028536)
• Investigation of Candidate Genes and Pathways in Basal/TNBC Patients by Integrated Analysis. (PMID:34184566)
• FOXD1 expression in head and neck squamous carcinoma: a study based on TCGA, GEO and meta-analysis. (PMID:34269372)
• FOXD1-AS1 upregulates FOXD1 to promote oral squamous cell carcinoma progression. (PMID:34403535)
• LINC00641 contributes to nasopharyngeal carcinoma cell malignancy through FOXD1 upregulation at the post-transcriptional level. (PMID:34767742)
• Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC. (PMID:34772357)
• Foxhead box D1 promotes the partial epithelial-to-mesenchymal transition of laryngeal squamous cell carcinoma cells via transcriptionally activating the expression of zinc finger protein 532. (PMID:35112956)
• Correlations between forkhead box D1 expression and clinicopathological characteristics of patients with bladder cancer and influence on biological behaviors of bladder cancer cells.", trans “Correlacion entre la expresion de Forkhead Box D1 y caracteristicas clinico-patologicas de pacientes con cancer de vejiga y su influencia en el comportamiento biologico de las celulas tumorales. (PMID:35435161)
• Combination of FOXD1 and Plk2: A novel biomarker for predicting unfavourable prognosis of colorectal cancer. (PMID:35579380)
• The Expression and Survival Significance of FOXD1 in Lung Squamous Cell Carcinoma: A Meta-Analysis, Immunohistochemistry Validation, and Bioinformatics Analysis. (PMID:35607308)
• USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1. (PMID:35974001)
• FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis. (PMID:36057597)
• FOXD1 promotes chemotherapy resistance by enhancing cell stemness in colorectal cancer through beta-catenin nuclear localization. (PMID:37203394)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxd2	ENSDARG00000058133
mus_musculus	Foxd1	ENSMUSG00000078302
rattus_norvegicus	Foxd1	ENSRNOG00000043332

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 D1 — Q16676 (reviewed: Q16676)

Alternative names: Forkhead-related protein FKHL8, Forkhead-related transcription factor 4

All UniProt accessions (1): Q16676

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in regulation of gene expression in a variety of processes, including formation of positional identity in the developing retina, regionalization of the optic chiasm, morphogenesis of the kidney, and neuralization of ectodermal cells. Involved in transcriptional activation of PGF and C3 genes.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_004463* (*=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 (20 total): sequence variant 12, compositionally biased region 4, region of interest 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16676-F1	59.00	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_METANEPHROS_DEVELOPMENT, MORF_MSH3, SASAI_TARGETS_OF_CXCR6_AND_PTCH1_UP, MORF_BRCA1, GOBP_POSITIVE_REGULATION_OF_KIDNEY_DEVELOPMENT, MENSE_HYPOXIA_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_NEUROGENESIS, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (20): regulation of transcription by RNA polymerase II (GO:0006357), axon guidance (GO:0007411), anatomical structure morphogenesis (GO:0009653), positive regulation of gene expression (GO:0010628), cell differentiation (GO:0030154), positive regulation of BMP signaling pathway (GO:0030513), luteinizing hormone secretion (GO:0032275), negative regulation of DNA-templated transcription (GO:0045892), canonical Wnt signaling pathway (GO:0060070), dichotomous subdivision of terminal units involved in ureteric bud branching (GO:0060678), nephrogenic mesenchyme development (GO:0072076), metanephric nephron development (GO:0072210), metanephric capsule development (GO:0072213), metanephric capsule specification (GO:0072267), positive regulation of kidney development (GO:0090184), branching involved in ureteric bud morphogenesis (GO:0001658), kidney development (GO:0001822), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944), pattern specification involved in metanephros development (GO:0072268)

GO Molecular Function (7): 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), DNA binding, bending (GO:0008301), 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	3
metanephros development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of gene expression	2
DNA-templated transcription	2
nephron development	2
regulation of transcription by RNA polymerase II	2
DNA binding	2
axonogenesis	1
neuron projection guidance	1
developmental process	1
anatomical structure development	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular developmental process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
gonadotropin secretion	1
negative regulation of RNA biosynthetic process	1
Wnt signaling pathway	1
branching involved in ureteric bud morphogenesis	1
dichotomous subdivision of an epithelial terminal unit	1
kidney mesenchyme development	1
renal capsule development	1
renal capsule specification	1
metanephric capsule formation	1
pattern specification involved in metanephros development	1
kidney development	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of kidney development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
animal organ development	1
renal system development	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
pattern specification process	1

Protein interactions and networks

STRING

1424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXD1	WT1	P19544	757
FOXD1	SIX2	Q9NPC8	739
FOXD1	PAX2	Q02962	596
FOXD1	SHH	Q15465	594
FOXD1	CITED1	Q99966	591
FOXD1	EPHB1	P54762	570
FOXD1	LHX1	P48742	550
FOXD1	EYA1	Q99502	537
FOXD1	WNT9B	O14905	536
FOXD1	EFNB2	P52799	526
FOXD1	SOX4	Q06945	518
FOXD1	LHX9	Q9NQ69	513
FOXD1	HOXB7	P09629	502
FOXD1	NKX2-1	P43699	493
FOXD1	FOXP2	O15409	480

IntAct

0 interactions, top by confidence:

BioGRID (7): FOXD1 (Affinity Capture-MS), FOXD1 (Affinity Capture-MS), FOXD1 (Affinity Capture-RNA), FOXD1 (Affinity Capture-Western), USP21 (Affinity Capture-Western), USP21 (Reconstituted Complex), FOXD1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8V0YY16, A2T7H5, A8MTJ6, B5RHS5, D3Z120, O00358, O35392, O35767, O54743, O60548, O88470, P09631, P18111, P23813, P31277, P42582, P47902, P52952, P58012, P78415, P79772, P81067, P84550, P84551, Q12947, Q12948, Q12952, Q16676, Q3I5G5, Q3Y598, Q4VUF1, Q61060, Q61345, Q61572, Q61850, Q62424, Q63244, Q63246, Q6VFT5, Q6VFT6

Diamond homologs: A0A1W2PRP0, A0A8V0YY16, A3KNJ3, A8MTJ6, B5RHS5, D3Z120, O00358, O35392, O43638, O60548, O88470, P32027, P32030, P35583, P55316, P56260, P58012, P79772, Q00939, Q02360, Q02361, Q12948, Q12950, Q12951, Q12952, Q13461, Q16676, Q18694, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q28D67, Q28HT3, Q32NP8, Q3I5G5, Q3SYB3, Q4VUF1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	30
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

19 predictions. Top by Δscore:

Variant	Effect	Δscore
5:73447708:T:TA	donor_gain	0.5300
5:73448145:T:TA	donor_gain	0.4300
5:73448148:T:TA	donor_gain	0.4300
5:73447176:G:T	acceptor_gain	0.4000
5:73448151:T:TA	donor_gain	0.3400
5:73448154:T:TA	donor_gain	0.3300
5:73446900:C:T	acceptor_gain	0.3100
5:73447625:C:CA	donor_gain	0.3100
5:73447711:T:TA	donor_gain	0.3000
5:73448268:T:TA	donor_gain	0.2900
5:73446897:G:GT	donor_gain	0.2500
5:73447175:C:CT	acceptor_gain	0.2400
5:73447552:AG:A	donor_gain	0.2400
5:73447709:C:A	donor_gain	0.2300
5:73447908:CAGAT:C	donor_gain	0.2300
5:73447139:T:TA	donor_gain	0.2200
5:73447016:C:A	donor_gain	0.2100
5:73447142:T:TA	donor_gain	0.2100
5:73447553:G:C	donor_gain	0.2100

AlphaMissense

2927 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:73447697:C:A	K222N	1.000
5:73447697:C:G	K222N	1.000
5:73447699:T:C	K222E	1.000
5:73447700:G:C	F221L	1.000
5:73447700:G:T	F221L	1.000
5:73447701:A:C	F221C	1.000
5:73447701:A:G	F221S	1.000
5:73447702:A:C	F221V	1.000
5:73447702:A:G	F221L	1.000
5:73447702:A:T	F221I	1.000
5:73447705:G:A	R220C	1.000
5:73447705:G:T	R220S	1.000
5:73447706:C:A	K219N	1.000
5:73447706:C:G	K219N	1.000
5:73447708:T:C	K219E	1.000
5:73447709:C:A	R218S	1.000
5:73447709:C:G	R218S	1.000
5:73447710:C:A	R218M	1.000
5:73447710:C:G	R218T	1.000
5:73447714:G:A	R217W	1.000
5:73447714:G:C	R217G	1.000
5:73447716:C:T	R216H	1.000
5:73447717:G:A	R216C	1.000
5:73447717:G:C	R216G	1.000
5:73447717:G:T	R216S	1.000
5:73447719:A:G	L215P	1.000
5:73447721:G:C	F214L	1.000
5:73447721:G:T	F214L	1.000
5:73447722:A:C	F214C	1.000
5:73447722:A:G	F214S	1.000

dbSNP variants (sampled 300 via entrez): RS1000924232 (5:73449670 T>A,G), RS1000932801 (5:73448690 G>A), RS1001482705 (5:73449907 G>A), RS1001658096 (5:73446531 AT>A), RS1002639284 (5:73450562 G>A), RS1003443177 (5:73450636 A>G), RS1004115094 (5:73447814 G>A,C), RS1004205267 (5:73446263 G>A,C), RS1004572980 (5:73448058 C>T), RS1005165848 (5:73449135 C>A), RS1005257564 (5:73448939 G>C), RS1005525009 (5:73448962 C>G), RS1005618201 (5:73449231 T>C), RS1005793770 (5:73446865 G>A,C), RS1006649259 (5:73449566 T>C)

Disease associations

OMIM: gene MIM:601091 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003476_8	Eyebrow thickness	3.000000e-07
GCST003477_7	Monobrow thickness	4.000000e-07
GCST003996_7	Monobrow	7.000000e-35
GCST006629_98	Pulse pressure	3.000000e-10
GCST006706_4	Eyebrow thickness	3.000000e-13
GCST006976_95	Macular thickness	8.000000e-09
GCST007269_256	Pulse pressure	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

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
Valproic Acid	affects expression, increases expression, increases methylation	4
bisphenol A	decreases expression, increases expression	3
Arsenic	increases abundance, increases expression, affects cotreatment	2
Estradiol	increases expression, affects cotreatment	2
sodium arsenate	increases abundance, increases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chloride	increases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
diallyl trisulfide	increases expression	1
rofecoxib	decreases expression	1
entinostat	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
ormosil	increases expression, affects binding	1
licochalcone B	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	increases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cannabidiol	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Coumestrol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases 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_A1X7	SEES3-1V human FOXD1, clone1	Embryonic stem cell	Male
CVCL_A1X8	SEES3-1V human FOXD1, clone2	Embryonic stem cell	Male
CVCL_A1X9	SEES3-1V human FOXD1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome