FOXD3

Summary

FOXD3 (forkhead box D3, HGNC:3804) is a protein-coding gene on chromosome 1p31.3, encoding Forkhead box protein D3 (Q9UJU5). Binds to the consensus sequence 5’-A[AT]T[AG]TTTGTTT-3’ and acts as a transcriptional repressor.

This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. Mutations in this gene cause autoimmune susceptibility 1.

Source: NCBI Gene 27022 — RefSeq curated summary.

At a glance

• Gene–disease (curated): anterior segment dysgenesis (Limited, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 89 total — 1 pathogenic
• Phenotypes (HPO): 4
• Transcription factor: yes — 15 downstream targets (CollecTRI)
• MANE Select transcript: NM_012183

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3804
Approved symbol	FOXD3
Name	forkhead box D3
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	Genesis, HFH2
Ensembl gene	ENSG00000187140
Ensembl biotype	protein_coding
OMIM	611539
Entrez	27022

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000371116

RefSeq mRNA: 1 — MANE Select: NM_012183 NM_012183

CCDS: CCDS624

Canonical transcript exons

ENST00000371116 — 1 exons

Exon	Start	End
ENSE00001454381	63322567	63325128

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 88.92.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5034 / max 41.7265, expressed in 316 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3169	1.4210	309
3170	0.0824	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	88.92	gold quality
tibial nerve	UBERON:0001323	83.82	gold quality
dorsal root ganglion	UBERON:0000044	77.19	gold quality
trigeminal ganglion	UBERON:0001675	75.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	68.79	gold quality
buccal mucosa cell	CL:0002336	67.72	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.14	gold quality
lower esophagus	UBERON:0013473	67.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	65.65	gold quality
mucosa of stomach	UBERON:0001199	60.80	gold quality
right atrium auricular region	UBERON:0006631	60.59	gold quality
cardiac atrium	UBERON:0002081	60.08	gold quality
seminal vesicle	UBERON:0000998	60.04	gold quality
tibialis anterior	UBERON:0001385	58.15	silver quality
colon	UBERON:0001155	57.75	gold quality
pancreatic ductal cell	CL:0002079	57.52	silver quality
large intestine	UBERON:0000059	57.00	gold quality
left coronary artery	UBERON:0001626	56.75	gold quality
esophagus	UBERON:0001043	55.48	gold quality
transverse colon	UBERON:0001157	55.39	gold quality
coronary artery	UBERON:0001621	55.26	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.91	gold quality
intestine	UBERON:0000160	54.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	54.58	gold quality
epithelial cell of pancreas	CL:0000083	54.35	gold quality
apex of heart	UBERON:0002098	54.28	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
endocervix	UBERON:0000458	53.65	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.86

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

15 targets.

Target	Regulation
CAPN6	Unknown
CNBP	Unknown
CYFIP2	Activation
FOXA1
FOXA2
IL10	Activation
MITF	Repression
NANOG	Unknown
NDRG1	Activation
NODAL	Activation
POU5F1	Unknown
RARB	Activation
RND3	Unknown
SPP1	Activation
ZNF175	Unknown

JASPAR motifs

Motif	Name	Family
MA0041.2	FOXD3	FOX
MA0041.3	FOXD3	FOX

JASPAR matrix evidence (PMIDs): PMID:8139574

Upstream regulators (CollecTRI, top): E2F1, E2F4, PAX3, SMAD4

miRNA regulators (miRDB)

39 targeting FOXD3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-3177-5P	99.65	70.38	1174

Literature-anchored findings (GeneRIF, showing 40)

• candidate for vitilago susceptibility and autosomal dominant with promoter variation (PMID:16098053)
• HIV-1 induces OTK18 expression through a YIN-YANG-1 mediated manner in human macrophages, although its gene expression is suppressed by FoxD3 upregulation (PMID:19034670)
• Studies show FOXD3 is suppressed by B-RAF, uncover a novel role and mechanism for FOXD3 as a negative cell cycle regulator, and have implications for the repression of melanocytic lineage cells. (PMID:20332228)
• FOXD3 regulates migration properties and Rnd3 expression in melanoma cells (PMID:21478267)
• Six nonsynonymous FOXD3 variants were identified in human ocular disease. (PMID:22815627)
• A balance of FOXD3 activity is required to maintain pluripotency and paraxial mesoderm fates. (PMID:22887036)
• Methylation profile analyses identified the promoter of FOXD3 as the only genomic region with increased methylation in mice and humans during progression of Helicobacter pylori-associated gastric tumors. (PMID:23058321)
• upregulation of ERBB3 is involved in melanoma adapting to RAF/MEK inhibitors through FOXD3 (PMID:23543055)
• Foxd3 is both sufficient and necessary for regulating the balance between melanocyte and Schwann cell development. In addition, Foxd3 is also sufficient to regulate the switch between neuronal and glial fates in sensory ganglia. (PMID:23858437)
• Results indicate that FOXD3 exhibits tumor suppressive activity that affects the growth, aggressiveness and angiogenesis of NB through transcriptional regulation of NDRG1. (PMID:24269992)
• Results suggest an inverse relationship between FoxD3 expression and tumor metastasis in invasive ductal carcinomas of the breast. (PMID:24551288)
• Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy. (PMID:24632201)
• Findings indicate that miR-137 is a valuable biomarker for hepatocellular carcinoma (HCC) prognosis and the forkhead box D3 (FoxD3)/miR-137/AKT2 regulatory network plays an important role in HCC progression. (PMID:24970808)
• FOXD3 and TWIST1 define distinct subgroups of cells within a heterogeneous tumor. (PMID:25061102)
• Results showed that silencing FoxD3 in lung cancer cell lines stimulated cell growth and inhibited cell apoptosis. (PMID:25894280)
• FOXD3 might serve as an independent prognostic biomarker and a potential therapeutic target for high-grade gliomas, which warrant further investigation. (PMID:26011451)
• Down-regulation of FOXD3 is associated with metastasis in hepatocellular carcinoma. (PMID:26112097)
• Data show that transcription factors PAX3 and FOXD3-mediated melanoma cell migration is dependent on promoting the expression of chemokine receptor CXCR4. (PMID:26205821)
• FOXD3 is sufficient but not necessary to drive PAX3 expression in melanoma cells. (PMID:26252164)
• In addition to a possible association of rs78645479 in FoxD3 with vitiligo, our data on the association of this FoxD3 variant with thyroid autoantibodies suggest a potential involvement of FoxD3 in thyroid immunoregulation. (PMID:26267147)
• FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. (PMID:26341266)
• The present study finds that the aspirin-FOXD3-OLA1P2-STAT3 axis exhibits exciting anticancer effects and provides new insights into the chemopreventive mechanisms underlying aspirin use (PMID:26898989)
• FOXO4 and FOXD3 were shown independently predictive of overall survival in gastric cancer (PMID:27027443)
• FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of colorectal cancer (PMID:27811858)
• Results show that FOXD3 expression was reduced in colon cancer cells. Its knockdown dramatically increased the proliferation of tumor cells, enhanced cell invasiveness and inhibited cell apoptosis. The study indicates that FOXD3 may play a protective role in human colon formation by regulating EGFR/Ras/Raf/MEK/ERK signal pathway. (PMID:27926503)
• total of 1799 differentially methylated regions were identified including SLC6A3, Rab40C, ZNF584, and FOXD3 whose significant methylation differences were confirmed in breast cancer patients through quantitative real-time polymerase chain reaction.Methylation of those aforementioned genes in white blood cells of our young patients may highlight their potential as early epimarkers (PMID:28349825)
• FOXD3 knockdown resulted in enhanced ATC proliferation, invasion and migration and diminished cellular apoptosis. Further, we showed that FOXD3 regulated expression of E-cadherin by modulating MAPK/EKR signaling pathway that promotes EMT and metastasis during thyroid carcinogenesis. (PMID:28430585)
• On the basis of these data, FOXD3 is a potent repressor of DCLK1-S expression in normal cells; loss of FOXD3 in hCCCs/hCRCs allows upregulation of DCLK1-S, imparting a potent invasive potential to the cells (PMID:28851816)
• FOXD3 acts as a repressor of the mitochondrial S-adenosylmethionine carrier (SLC25A26) gene expression in cancer cells. (PMID:30076902)
• Tuning Forkhead Box D3 overexpression to promote specific osteogenic differentiation of human embryonic stem cells while reducing pluripotency in a three-dimensional culture system. (PMID:30350469)
• Serum FOXD3 expression was weakly expressed in NSCLC patients compared to the controls at mRNA and protein levels (P<0.001) and low FOXD3 expression was positively correlated with TNM stage, lymph node metastasis, and differentiation. (PMID:30596382)
• we found that FOXD3 represses WDR5, which regulates TIC-related signaling pathway. Moreover, WDR5 were positively correlated with the TIC abundance and tumor progression. Besides, patients with high expression of WDR5 presented a poorer overall survival. FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer (PMID:30703266)
• the present results demonstrated that miR4255p promoted hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion by suppressing FOXD3 expression, potentially providing a novel target for the treatment of HCC. (PMID:31257522)
• The FOXD3 regulates the balance of human ESCs between pluripotency and meso-endoderm fates, which adds to our understanding of the role of FOXD3 in humans. (PMID:31415841)
• FOXD3, frequently methylated in colorectal cancer, acts as a tumor suppressor and induces tumor cell apoptosis under ER stress via p53. (PMID:31784734)
• FOXD3 Regulates VISTA Expression in Melanoma. (PMID:31940493)
• LncRNA FOXD3-AS1 Mediates AKT Pathway to Promote Growth and Invasion in Hepatocellular Carcinoma Through Regulating RICTOR. (PMID:32191537)
• Highly expressed lncRNA FOXD3-AS1 promotes non-small cell lung cancer progression via regulating miR-127-3p/mediator complex subunit 28 axis. (PMID:32196603)
• FOXD3 inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma through regulation of the PI3K-Akt pathway. (PMID:32459973)
• Long non-coding RNA FOXD3-AS1 silencing exerts tumor suppressive effects in nasopharyngeal carcinoma by downregulating FOXD3 expression via microRNA-185-3p upregulation. (PMID:33204001)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxd3	ENSDARG00000021032
mus_musculus	Foxd3	ENSMUSG00000067261
rattus_norvegicus	Foxd3	ENSRNOG00000066522

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), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein D3 — Q9UJU5 (reviewed: Q9UJU5)

Alternative names: HNF3/FH transcription factor genesis

All UniProt accessions (1): Q9UJU5

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the consensus sequence 5’-A[AT]T[AG]TTTGTTT-3’ and acts as a transcriptional repressor. Also acts as a transcriptional activator. Negatively regulates transcription of transcriptional repressor RHIT/ZNF205. Promotes development of neural crest cells from neural tube progenitors. Restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation. Required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis.

Subunit / interactions. Interacts with POU5F1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in chronic myeloid leukemia, Jurkat T-cell leukemia and teratocarcinoma cell lines, but not in any other cell lines or normal tissues examined.

Disease relevance. Autoimmune disease 1 (AIS1) [MIM:607836] An autoimmune disorder characterized by the association of vitiligo with autoimmune thyroiditis (Hashimoto thyroiditis). Disease susceptibility is associated with variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_036315* (*=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
IPR047392	FH_FOXD3	Domain
IPR050211	FOX_domain-containing	Family

Pfam: PF00250

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJU5-F1	57.17	0.14

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2892247	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity

MSigDB gene sets: 170 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, ATF_B, AHRARNT_01, RNGTGGGC_UNKNOWN, RRAGTTGT_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BENPORATH_ES_WITH_H3K27ME3, AREB6_01, AP4_Q6, CREBP1_Q2, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, EFC_Q6, CREB_Q4, NFKB_C

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), regulation of transcription by RNA polymerase II (GO:0006357), anatomical structure morphogenesis (GO:0009653), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transcriptional regulation of pluripotent stem cells	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
developmental process	1
anatomical structure development	1
cellular developmental process	1
positive regulation of DNA-templated transcription	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
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXD3	POU5F1	P31359	909
FOXD3	SNAI2	O43623	794
FOXD3	SOX10	P56693	785
FOXD3	SOX2	P48431	767
FOXD3	PRDM14	Q9GZV8	762
FOXD3	SOX9	P48436	752
FOXD3	PAX3	P23760	716
FOXD3	SMARCA4	P51532	687
FOXD3	ZIC1	Q15915	679
FOXD3	LIN28A	Q9H9Z2	663
FOXD3	BMP4	P12644	653
FOXD3	PAX6	P26367	646
FOXD3	MITF	O75030	643
FOXD3	MSX1	P28360	640
FOXD3	SNAI1	O95863	632

IntAct

9 interactions, top by confidence:

A	B	Type	Score
FOXD3	POU5F1	psi-mi:“MI:0915”(physical association)	0.520
POU5F1	FOXD3	psi-mi:“MI:0915”(physical association)	0.520
FOXD3	HOXC13	psi-mi:“MI:0914”(association)	0.350
FOXD3	MYL12B	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
FOXD3	CLUH	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): FOXD1 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), CUX1 (Affinity Capture-MS), TOP2A (Affinity Capture-MS), TOP2B (Affinity Capture-MS), LIG3 (Affinity Capture-MS), VRK3 (Affinity Capture-MS), UBP1 (Affinity Capture-MS), MYL12B (Affinity Capture-MS), SATB1 (Affinity Capture-MS), XRCC1 (Affinity Capture-MS), DRAP1 (Affinity Capture-MS), HOXB9 (Affinity Capture-MS), MYL9 (Affinity Capture-MS)

ESM2 similar proteins: A2A9A2, A4QNP7, A6QQ94, A6YP92, A7M7C7, A7MB54, B5RHS5, M0R6D8, O09029, O35085, P28360, P41225, P43694, P46153, P50548, P78414, P78415, P79772, P81067, P81068, P84550, P84551, Q08369, Q0Q0E4, Q14549, Q14774, Q2I327, Q2MJB4, Q2VL84, Q2VL87, Q2VL88, Q2VWA4, Q3SZJ5, Q4AE28, Q61169, Q61345, Q6YHU8, Q71T09, Q76L87, Q7TQ40

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	81
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
441647	GRCh37/hg19 1p31.3-31.1(chr1:61351024-79583933)x1	Pathogenic

SpliceAI

16 predictions. Top by Δscore:

Variant	Effect	Δscore
1:63324928:A:C	acceptor_gain	0.5100
1:63323187:T:TA	donor_gain	0.4000
1:63323308:G:GT	donor_gain	0.2900
1:63324422:A:AG	acceptor_gain	0.2500
1:63324423:G:GG	acceptor_gain	0.2500
1:63324404:GC:G	acceptor_gain	0.2400
1:63324214:G:GA	donor_gain	0.2300
1:63324217:G:T	donor_gain	0.2300
1:63324215:G:A	donor_gain	0.2200
1:63323164:G:GT	donor_gain	0.2100
1:63324213:T:TA	donor_gain	0.2100
1:63324216:G:GT	donor_gain	0.2100
1:63324424:T:G	acceptor_gain	0.2100
1:63324377:C:CT	acceptor_gain	0.2000
1:63324417:CGG:C	acceptor_gain	0.2000
1:63324418:G:C	acceptor_gain	0.2000

AlphaMissense

3045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:63323479:A:C	K141Q	1.000
1:63323479:A:G	K141E	1.000
1:63323480:A:T	K141M	1.000
1:63323481:G:C	K141N	1.000
1:63323481:G:T	K141N	1.000
1:63323482:C:A	P142T	1.000
1:63323482:C:G	P142A	1.000
1:63323482:C:T	P142S	1.000
1:63323483:C:A	P142Q	1.000
1:63323483:C:G	P142R	1.000
1:63323483:C:T	P142L	1.000
1:63323485:C:A	P143T	1.000
1:63323486:C:A	P143H	1.000
1:63323486:C:T	P143L	1.000
1:63323488:T:A	Y144N	1.000
1:63323488:T:C	Y144H	1.000
1:63323488:T:G	Y144D	1.000
1:63323489:A:G	Y144C	1.000
1:63323491:T:C	S145P	1.000
1:63323492:C:G	S145W	1.000
1:63323492:C:T	S145L	1.000
1:63323494:T:A	Y146N	1.000
1:63323494:T:C	Y146H	1.000
1:63323494:T:G	Y146D	1.000
1:63323495:A:G	Y146C	1.000
1:63323497:A:T	I147F	1.000
1:63323498:T:A	I147N	1.000
1:63323498:T:C	I147T	1.000
1:63323498:T:G	I147S	1.000
1:63323500:G:A	A148T	1.000

dbSNP variants (sampled 300 via entrez): RS1000159787 (1:63321400 G>A,C,T), RS1000361513 (1:63320936 C>T), RS1000615003 (1:63321757 T>A,C,G), RS1000740343 (1:63320621 C>T), RS1001302357 (1:63324407 T>A,G), RS1002472593 (1:63324033 G>A,C,T), RS1002747252 (1:63322347 C>A), RS1003598991 (1:63325472 A>T), RS1004361636 (1:63321821 T>C), RS1004509569 (1:63322339 G>A), RS1004858413 (1:63322151 G>A,C,T), RS1004884333 (1:63321528 G>A,C,T), RS1004971454 (1:63325000 T>A), RS1006584306 (1:63323160 G>A,C,T), RS1008161631 (1:63322442 T>C)

Disease associations

OMIM: gene MIM:611539 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
anterior segment dysgenesis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
aniridia	Disputed	AD

Mondo (1): anterior segment dysgenesis (MONDO:0019503)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000872	Hashimoto thyroiditis
HP:0001045	Vitiligo
HP:0003621	Juvenile onset

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
trichostatin A	affects cotreatment, increases expression, decreases expression	3
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
belinostat	affects cotreatment, increases expression	2
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases methylation, decreases expression	2
methylmercuric chloride	decreases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, decreases expression	1
Chir 99021	affects binding, affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
XAV939	decreases expression, affects binding, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic	affects methylation	1
Ascorbic Acid	decreases expression, affects binding, affects cotreatment	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Hydrocortisone	affects cotreatment, decreases expression	1
Parathion	increases 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_A1Y0	SEES3-1V human FOXD3, clone1	Embryonic stem cell	Male
CVCL_A1Y1	SEES3-1V human FOXD3, clone2	Embryonic stem cell	Male
CVCL_A1Y2	SEES3-1V human FOXD3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05641103	Not specified	COMPLETED	PREDIGA 2: Spanish Acronym of Educational and Diagnostic Project for Gaucher and ASMD