FOXH1 (forkhead box H1)

Gene

• Entrez ID: 8928
• Gene name: Forkhead box H1
• Gene symbol: FOXH1
• Synonyms (NCBI Gene): FAST-1, FAST1
• Chromosome: 8
• Chromosome location: 8q24.3
• Summary: FOXH1 encodes a human homolog of Xenopus forkhead activin signal transducer-1. FOXH1 protein binds SMAD2 and activates an activin response element via binding the DNA motif TGT(G/T)(T/G)ATT. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs374587860	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT528122	hsa-miR-6779-3p	PAR-CLIP	22012620
MIRT528121	hsa-miR-1245a	PAR-CLIP	22012620
MIRT528120	hsa-miR-8079	PAR-CLIP	22012620
MIRT528119	hsa-miR-361-3p	PAR-CLIP	22012620
MIRT528118	hsa-miR-7108-3p	PAR-CLIP	22012620
MIRT528117	hsa-miR-370-3p	PAR-CLIP	22012620
MIRT528116	hsa-miR-6893-3p	PAR-CLIP	22012620
MIRT528115	hsa-miR-93-3p	PAR-CLIP	22012620
MIRT528114	hsa-miR-4795-5p	PAR-CLIP	22012620
MIRT528113	hsa-miR-3173-5p	PAR-CLIP	22012620
MIRT528112	hsa-miR-6799-3p	PAR-CLIP	22012620
MIRT528111	hsa-miR-4763-5p	PAR-CLIP	22012620
MIRT528110	hsa-miR-1271-3p	PAR-CLIP	22012620
MIRT528109	hsa-miR-550a-3-5p	PAR-CLIP	22012620
MIRT528108	hsa-miR-550a-5p	PAR-CLIP	22012620
MIRT528107	hsa-miR-6802-3p	PAR-CLIP	22012620
MIRT528106	hsa-miR-3616-5p	PAR-CLIP	22012620
MIRT528105	hsa-miR-573	PAR-CLIP	22012620
MIRT528104	hsa-miR-6894-3p	PAR-CLIP	22012620
MIRT528122	hsa-miR-6779-3p	PAR-CLIP	22012620
MIRT528121	hsa-miR-1245a	PAR-CLIP	22012620
MIRT528120	hsa-miR-8079	PAR-CLIP	22012620
MIRT528119	hsa-miR-361-3p	PAR-CLIP	22012620
MIRT528118	hsa-miR-7108-3p	PAR-CLIP	22012620
MIRT528117	hsa-miR-370-3p	PAR-CLIP	22012620
MIRT528116	hsa-miR-6893-3p	PAR-CLIP	22012620
MIRT528115	hsa-miR-93-3p	PAR-CLIP	22012620
MIRT528114	hsa-miR-4795-5p	PAR-CLIP	22012620
MIRT528113	hsa-miR-3173-5p	PAR-CLIP	22012620
MIRT528112	hsa-miR-6799-3p	PAR-CLIP	22012620
MIRT528111	hsa-miR-4763-5p	PAR-CLIP	22012620
MIRT528110	hsa-miR-1271-3p	PAR-CLIP	22012620
MIRT528109	hsa-miR-550a-3-5p	PAR-CLIP	22012620
MIRT528108	hsa-miR-550a-5p	PAR-CLIP	22012620
MIRT528107	hsa-miR-6802-3p	PAR-CLIP	22012620
MIRT528106	hsa-miR-3616-5p	PAR-CLIP	22012620
MIRT528105	hsa-miR-573	PAR-CLIP	22012620
MIRT528104	hsa-miR-6894-3p	PAR-CLIP	22012620
MIRT1001647	hsa-miR-1193	CLIP-seq
MIRT1001648	hsa-miR-1253	CLIP-seq
MIRT1001649	hsa-miR-1587	CLIP-seq
MIRT1001650	hsa-miR-3132	CLIP-seq
MIRT1001651	hsa-miR-3134	CLIP-seq
MIRT1001652	hsa-miR-4251	CLIP-seq
MIRT1001653	hsa-miR-4417	CLIP-seq
MIRT1001654	hsa-miR-4492	CLIP-seq
MIRT1001655	hsa-miR-4498	CLIP-seq
MIRT1001656	hsa-miR-452	CLIP-seq
MIRT1001657	hsa-miR-4534	CLIP-seq
MIRT1001658	hsa-miR-4656	CLIP-seq
MIRT1001659	hsa-miR-4675	CLIP-seq
MIRT1001660	hsa-miR-4676-3p	CLIP-seq
MIRT1001661	hsa-miR-4684-3p	CLIP-seq
MIRT1001662	hsa-miR-4693-5p	CLIP-seq
MIRT1001663	hsa-miR-4727-3p	CLIP-seq
MIRT1001664	hsa-miR-4741	CLIP-seq
MIRT1001665	hsa-miR-518a-5p	CLIP-seq
MIRT1001666	hsa-miR-527	CLIP-seq
MIRT1001667	hsa-miR-762	CLIP-seq
MIRT1996822	hsa-miR-1184	CLIP-seq
MIRT1996823	hsa-miR-1301	CLIP-seq
MIRT1996824	hsa-miR-1976	CLIP-seq
MIRT1996825	hsa-miR-24	CLIP-seq
MIRT1996826	hsa-miR-3155	CLIP-seq
MIRT1996827	hsa-miR-3155b	CLIP-seq
MIRT1996828	hsa-miR-4268	CLIP-seq
MIRT1996829	hsa-miR-4448	CLIP-seq
MIRT1996830	hsa-miR-4660	CLIP-seq
MIRT1996831	hsa-miR-4690-3p	CLIP-seq
MIRT1996832	hsa-miR-484	CLIP-seq
MIRT1996833	hsa-miR-5047	CLIP-seq
MIRT2230759	hsa-miR-1254	CLIP-seq
MIRT2230760	hsa-miR-3116	CLIP-seq
MIRT2230761	hsa-miR-4728-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000785	Component	Chromatin	IDA	21828274
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IBA
GO:0000976	Function	Transcription cis-regulatory region binding	IEA
GO:0000976	Function	Transcription cis-regulatory region binding	ISS
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0000987	Function	Cis-regulatory region sequence-specific DNA binding	IC	21828274
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IBA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0001947	Process	Heart looping	IEA
GO:0001947	Process	Heart looping	ISS
GO:0003139	Process	Secondary heart field specification	IEA
GO:0003139	Process	Secondary heart field specification	ISS
GO:0003140	Process	Determination of left/right asymmetry in lateral mesoderm	NAS	17507406
GO:0003151	Process	Outflow tract morphogenesis	IEA
GO:0003151	Process	Outflow tract morphogenesis	ISS
GO:0003215	Process	Cardiac right ventricle morphogenesis	IEA
GO:0003215	Process	Cardiac right ventricle morphogenesis	ISS
GO:0003222	Process	Ventricular trabecula myocardium morphogenesis	IEA
GO:0003222	Process	Ventricular trabecula myocardium morphogenesis	ISS
GO:0003677	Function	DNA binding	IDA	9389648
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	17438144
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003714	Function	Transcription corepressor activity	IDA	16120611
GO:0005515	Function	Protein binding	IPI	9702198, 16120611, 17474147, 21828274, 32296183
GO:0005634	Component	Nucleus	IC	9702198
GO:0005634	Component	Nucleus	IDA	16120611
GO:0005634	Component	Nucleus	IEA
GO:0005667	Component	Transcription regulator complex	IDA	17438144
GO:0005667	Component	Transcription regulator complex	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IBA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IEA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	ISS
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS	9702198
GO:0007368	Process	Determination of left/right symmetry	IEA
GO:0009952	Process	Anterior/posterior pattern specification	IEA
GO:0019904	Function	Protein domain specific binding	IPI	9702198
GO:0032444	Component	Activin responsive factor complex	IBA
GO:0032444	Component	Activin responsive factor complex	IDA	9389648
GO:0032444	Component	Activin responsive factor complex	IEA
GO:0035054	Process	Embryonic heart tube anterior/posterior pattern specification	IEA
GO:0035909	Process	Aorta morphogenesis	IEA
GO:0035909	Process	Aorta morphogenesis	ISS
GO:0038092	Process	Nodal signaling pathway	NAS	17507406
GO:0043425	Function	BHLH transcription factor binding	IPI	21828274
GO:0043565	Function	Sequence-specific DNA binding	IDA	9702198
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	9389648, 9702198
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	9702198
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	14671321
GO:0046332	Function	SMAD binding	IEA
GO:0046332	Function	SMAD binding	IPI	21828274
GO:0048318	Process	Axial mesoderm development	IEA
GO:0050681	Function	Nuclear androgen receptor binding	IPI	16120611
GO:0060766	Process	Negative regulation of androgen receptor signaling pathway	IDA	16120611
GO:0070365	Process	Hepatocyte differentiation	IEA
GO:0070410	Function	Co-SMAD binding	IMP	16120611
GO:0070412	Function	R-SMAD binding	IEA
GO:0070412	Function	R-SMAD binding	IMP	16120611
GO:0070412	Function	R-SMAD binding	IPI	9389648, 9702198
GO:0071345	Process	Cellular response to cytokine stimulus	IMP	14671321
GO:0140297	Function	DNA-binding transcription factor binding	IPI	18922797

Other IDs

• MIM: 603621
• HGNC: 3814
• e!Ensembl: ENSG00000160973

Protein

• UniProt ID: O75593
• Protein name: Forkhead box protein H1 (Forkhead activin signal transducer 1) (Fast-1) (hFAST-1) (Forkhead activin signal transducer 2) (Fast-2)
• Protein function: Transcriptional activator. Recognizes and binds to the DNA sequence 5'-TGT[GT][GT]ATT-3'. Required for induction of the goosecoid (GSC) promoter by TGF-beta or activin signaling. Forms a transcriptionally active complex containing FOXH1/SMAD2/SM
• PDB: 5XOC, 7YZB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00250	Forkhead	32 → 116	Forkhead domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9702198}.
• Sequence:

  MGPCSGSRLGPPEAESPSQPPKRRKKRYLRHDKPPYTYLAMIALVIQAAPSRRLKLAQII
  RQVQAVFPFFREDYEGWKDSIRHNLSSNRCFRKVPKDPAKPQAKGNFWAVDVSLIPAEAL
  RLQNTALCRRWQNGGARGAFAKDLGPYVLHGRPYRPPSPPPPPSEGFSIKSLLGGSGEGA
  PWPGLAPQSSPVPAGTGNSGEEAVPTPPLPSSERPLWPLCPLPGPTRVEGETVQGGAIGP
  STLSPEPRAWPLHLLQGTAVPGGRSSGGHRASLWGQLPTSYLPIYTPNVVMPLAPPPTSC
  PQCPSTSPAYWGVAPETRGPPGLLCDLDALFQGVPPNKSIYDVWVSHPRDLAAPGPGWLL
  SWCSL

• Sequence length: 365

Pathways

Reactome:

Signaling by NODAL
Signaling by Activin

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Conotruncal defect	Likely pathogenic	rs1564752095, rs1379104498, rs1825112395, rs1825112515, rs1312980498, rs1341550325	RCV001175382 RCV001175383 RCV001175385 RCV001175386 RCV001175387 RCV001175388	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CBL-related disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART MALFORMATION	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART MALFORMATIONS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONOTRUNCAL HEART DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FOXH1-related disorder	Likely benign; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HOLOPROSENCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Holoprosencephaly sequence	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LOBAR HOLOPROSENCEPHALY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROFORM HOLOPROSENCEPHALY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIDDLE INTERHEMISPHERIC VARIANT OF HOLOPROSENCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIDLINE INTERHEMISPHERIC VARIANT OF HOLOPROSENCEPHALY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MYELOMONOCYTIC LEUKEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEMI-LOBAR HOLOPROSENCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEMILOBAR HOLOPROSENCEPHALY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEPTOPREOPTIC HOLOPROSENCEPHALY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TETRALOGY OF FALLOT	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Alobar Holoprosencephaly	Alobar Holoprosencephaly	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
Alobar holoprosencephaly	Alobar Holoprosencephaly	Orphanet			★☆☆☆☆ Found in Text Mining only
Ambiguous Genitalia	Ambiguous Genitalia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Asplenia Syndrome	Asplenia	BEFREE	27329052		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	25409762	Associate	★☆☆☆☆ Found in Text Mining only
Choanal Atresia	Choanal Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30594391		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of kidneys syndrome	Renal agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital coloboma of iris	Congenital Coloboma Of Iris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	18538293		★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conotruncal cardiac defects	Conotruncal cardiac defect	Pubtator	37406974	Associate	★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	25482028		★☆☆☆☆ Found in Text Mining only
Cyclocephaly	Cyclocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Duodenal atresia	Duodenal Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
FRIEDREICH ATAXIA 1	Friedreich Ataxia	BEFREE	30464193		★☆☆☆☆ Found in Text Mining only
Head and Neck Carcinoma	Head And Neck Carcinoma	BEFREE	24719202		★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	32078439	Associate	★☆☆☆☆ Found in Text Mining only
Hemangioma	Hemangioma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Holoprosencephaly	Holoprosencephaly	BEFREE	18538293, 21183895		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Holoprosencephaly	Holoprosencephaly	LHGDN	18538293		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Holoprosencephaly	Holoprosencephaly	GENOMICS_ENGLAND_DG	27363716		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Holoprosencephaly	Holoprosencephaly	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lobar Holoprosencephaly	Lobar Holoprosencephaly	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lobar holoprosencephaly	Lobar Holoprosencephaly	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant Head and Neck Neoplasm	Head and neck cancer	BEFREE	24719202		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	16120611, 25409762		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microform holoprosencephaly	Microform Holoprosencephaly	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Midline interhemispheric variant of holoprosencephaly	Midline Interhemispheric Variant Of Holoprosencephaly	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myeloid Leukemia	Myeloid Leukemia	BEFREE	31068365		★☆☆☆☆ Found in Text Mining only
Panhypopituitarism	Panhypopituitarism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	16120611, 25409762		★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	25482028		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Semilobar Holoprosencephaly	Semilobar Holoprosencephaly	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Semilobar holoprosencephaly	Semilobar Holoprosencephaly	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Septopreoptic holoprosencephaly	Septopreoptic Holoprosencephaly	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs ambiguus	Situs ambiguus	BEFREE	27329052		★☆☆☆☆ Found in Text Mining only
SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR	Fused incisors	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	CTD_human_DG	25093829		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tetralogy of Fallot	Tetralogy of fallot	Pubtator	25093829	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Transposition of Great Vessels	Transposition Of Great Vessels	BEFREE	27329052		★☆☆☆☆ Found in Text Mining only
Transposition of Great Vessels	Transposition of the great arteries	Pubtator	32078439	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	BEFREE	19525021		★☆☆☆☆ Found in Text Mining only