FOXD3

forkhead box D3, the group of Forkhead boxes

Basic information

Region (hg38): 1:63322567-63325128

Links

ENSG00000187140 ∙ NCBI:27022 ∙ OMIM:611539 ∙ HGNC:3804 ∙ Uniprot:Q9UJU5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• aniridia (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXD3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXD3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7		7
missense			36		1	37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	36	7	1

Variants in FOXD3

This is a list of pathogenic ClinVar variants found in the FOXD3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-63323197-C-A		not specified	Uncertain significance (Feb 21, 2024)
1-63323207-C-T		not specified	Uncertain significance (Jan 24, 2024)
1-63323249-C-A		not specified	Uncertain significance (Jun 22, 2024)
1-63323303-C-T		not specified	Uncertain significance (Oct 02, 2023)
1-63323315-C-T		not specified	Uncertain significance (Jun 29, 2023)
1-63323324-G-A		FOXD3-related disorder	Uncertain significance (Nov 22, 2023)
1-63323344-G-T		FOXD3-related disorder	Benign (Dec 05, 2019)
1-63323416-C-A		not specified	Uncertain significance (Mar 20, 2023)
1-63323419-G-A		not specified	Uncertain significance (Aug 17, 2021)
1-63323453-C-A		not specified	Uncertain significance (Oct 26, 2022)
1-63323462-C-G		not specified	Uncertain significance (Jan 31, 2022)
1-63323490-C-T		FOXD3-related disorder	Likely benign (Sep 13, 2021)
1-63323593-A-G		not specified	Uncertain significance (May 26, 2024)
1-63323697-C-T			Benign/Likely benign (Jan 01, 2023)
1-63323740-G-C		not specified	Uncertain significance (Jun 01, 2023)
1-63323778-C-T		FOXD3-related disorder	Likely benign (Mar 27, 2019)
1-63323807-C-T		not specified	Uncertain significance (Jan 02, 2024)
1-63323849-C-G		not specified	Uncertain significance (Jun 11, 2021)
1-63323855-G-C		not specified	Uncertain significance (Aug 09, 2021)
1-63323861-C-G		not specified	Uncertain significance (Nov 12, 2021)
1-63323861-C-T		not specified	Uncertain significance (Apr 24, 2024)
1-63323862-G-C		FOXD3-related disorder	Likely benign (Feb 22, 2019)
1-63323884-G-C		not specified	Uncertain significance (Feb 07, 2023)
1-63323893-C-A		not specified	Uncertain significance (Aug 22, 2023)
1-63323900-C-T		not specified	Uncertain significance (Sep 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXD3	protein_coding	protein_coding	ENST00000371116	1	2068

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.582	0.408	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.951	158	195	0.809	0.00000916	2953
Missense in Polyphen		24	53.281	0.45045		628
Synonymous	-0.758	99	89.9	1.10	0.00000465	1076
Loss of Function	2.08	1	6.91	0.145	2.98e-7	103

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. 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. {ECO:0000269|PubMed:11891324}.
• Pathway: Neural Crest Differentiation;POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation;Wnt Signaling Pathway and Pluripotency;Developmental Biology;POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation;Transcriptional regulation of pluripotent stem cells (Consensus)

Recessive Scores

• pRec: 0.224

Haploinsufficiency Scores

• pHI: 0.608
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.500

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Foxd3
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); craniofacial phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: foxd3
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;in utero embryonic development;regulation of transcription by RNA polymerase II;anatomical structure morphogenesis;cell differentiation;somatic stem cell population maintenance;positive regulation of transcription by RNA polymerase II
• Cellular component: nuclear chromatin;nucleus;nucleoplasm
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding