ZIC3 (Zic family zinc finger 3)

Gene

• Entrez ID: 7547
• Gene name: Zic family zinc finger 3
• Gene symbol: ZIC3
• Synonyms: HTX, HTX1, VACTERLX, ZNF203
• Chromosome: X
• Chromosome location: Xq26.3
• Summary: This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy,

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894960	C>T	Pathogenic	Coding sequence variant, stop gained
rs104894961	G>C	Pathogenic	Coding sequence variant, missense variant
rs104894962	A>G	Pathogenic	Coding sequence variant, missense variant
rs122462165	C>T	Pathogenic	Coding sequence variant, missense variant
rs122462166	C>A	Pathogenic	Coding sequence variant, stop gained
rs122463167	T>A	Pathogenic	Coding sequence variant, missense variant
rs122463168	T>G	Pathogenic	Coding sequence variant, missense variant
rs143990850	G>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs147232392	G>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign, benign-likely-benign, benign	Missense variant, coding sequence variant
rs387906498	A>T	Pathogenic	Stop gained, coding sequence variant
rs398122850	->GCCGCC	Pathogenic	Inframe insertion, coding sequence variant
rs748325646	CGCCGCCGCCGCCGC>-,CGC,CGCCGC,CGCCGCCGC,CGCCGCCGCCGC,CGCCGCCGCCGCCGCCGC,CGCCGCCGCCGCCGCCGCCGC,CGCCGCCGCCGCCGCCGCCGCCGC,CGCCGCCGCCGCCGCCGCCGCCGCCGC	Likely-benign, uncertain-significance, benign, conflicting-interpretations-of-pathogenicity	Inframe insertion, inframe deletion, coding sequence variant
rs763534805	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs886041111	G>C	Likely-pathogenic	Missense variant, coding sequence variant
rs886042663	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1203069392	C>A,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs1556029841	ACTT>-	Pathogenic	Frameshift variant, coding sequence variant
rs1569345504	C>A	Pathogenic	Coding sequence variant, stop gained
rs1569345723	->G	Pathogenic	Coding sequence variant, frameshift variant
rs1569345742	CATACCGCCCAGTGGCC>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602742808	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602743059	C>T	Likely-pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000976	hsa-miR-155-5p	Luciferase reporter assay	18367535
MIRT000976	hsa-miR-155-5p	Luciferase reporter assay	18367535
MIRT000976	hsa-miR-155-5p	Luciferase reporter assay	19177201
MIRT000976	hsa-miR-155-5p	Review	20026422
MIRT000976	hsa-miR-155-5p	Other	20584899
MIRT1513422	hsa-miR-1224-5p	CLIP-seq
MIRT1513423	hsa-miR-1227	CLIP-seq
MIRT1513424	hsa-miR-1271	CLIP-seq
MIRT1513425	hsa-miR-1304	CLIP-seq
MIRT1513426	hsa-miR-155	CLIP-seq
MIRT1513427	hsa-miR-182	CLIP-seq
MIRT1513428	hsa-miR-208a	CLIP-seq
MIRT1513429	hsa-miR-208b	CLIP-seq
MIRT1513430	hsa-miR-219-2-3p	CLIP-seq
MIRT1513431	hsa-miR-2964a-3p	CLIP-seq
MIRT1513432	hsa-miR-3117-5p	CLIP-seq
MIRT1513433	hsa-miR-3616-5p	CLIP-seq
MIRT1513434	hsa-miR-3617	CLIP-seq
MIRT1513435	hsa-miR-3647-5p	CLIP-seq
MIRT1513436	hsa-miR-3653	CLIP-seq
MIRT1513437	hsa-miR-3658	CLIP-seq
MIRT1513438	hsa-miR-3688-3p	CLIP-seq
MIRT1513439	hsa-miR-383	CLIP-seq
MIRT1513440	hsa-miR-3915	CLIP-seq
MIRT1513441	hsa-miR-3928	CLIP-seq
MIRT1513442	hsa-miR-4261	CLIP-seq
MIRT1513443	hsa-miR-4264	CLIP-seq
MIRT1513444	hsa-miR-4267	CLIP-seq
MIRT1513445	hsa-miR-4426	CLIP-seq
MIRT1513446	hsa-miR-4432	CLIP-seq
MIRT1513447	hsa-miR-4457	CLIP-seq
MIRT1513448	hsa-miR-455-5p	CLIP-seq
MIRT1513449	hsa-miR-4647	CLIP-seq
MIRT1513450	hsa-miR-4662b	CLIP-seq
MIRT1513451	hsa-miR-4680-3p	CLIP-seq
MIRT1513452	hsa-miR-4689	CLIP-seq
MIRT1513453	hsa-miR-4700-3p	CLIP-seq
MIRT1513454	hsa-miR-4738-3p	CLIP-seq
MIRT1513455	hsa-miR-4772-5p	CLIP-seq
MIRT1513456	hsa-miR-4797-3p	CLIP-seq
MIRT1513457	hsa-miR-4803	CLIP-seq
MIRT1513458	hsa-miR-499-5p	CLIP-seq
MIRT1513459	hsa-miR-513b	CLIP-seq
MIRT1513460	hsa-miR-564	CLIP-seq
MIRT1513461	hsa-miR-573	CLIP-seq
MIRT1513462	hsa-miR-576-3p	CLIP-seq
MIRT1513463	hsa-miR-584	CLIP-seq
MIRT1513464	hsa-miR-605	CLIP-seq
MIRT1513465	hsa-miR-622	CLIP-seq
MIRT1513466	hsa-miR-641	CLIP-seq
MIRT1513467	hsa-miR-96	CLIP-seq
MIRT1513422	hsa-miR-1224-5p	CLIP-seq
MIRT1513425	hsa-miR-1304	CLIP-seq
MIRT1513440	hsa-miR-3915	CLIP-seq
MIRT1513441	hsa-miR-3928	CLIP-seq
MIRT1513452	hsa-miR-4689	CLIP-seq
MIRT1513422	hsa-miR-1224-5p	CLIP-seq
MIRT1513425	hsa-miR-1304	CLIP-seq
MIRT1513426	hsa-miR-155	CLIP-seq
MIRT2154750	hsa-miR-3668	CLIP-seq
MIRT1513440	hsa-miR-3915	CLIP-seq
MIRT1513441	hsa-miR-3928	CLIP-seq
MIRT1513447	hsa-miR-4457	CLIP-seq
MIRT1513452	hsa-miR-4689	CLIP-seq
MIRT1513459	hsa-miR-513b	CLIP-seq
MIRT1513422	hsa-miR-1224-5p	CLIP-seq
MIRT1513425	hsa-miR-1304	CLIP-seq
MIRT1513426	hsa-miR-155	CLIP-seq
MIRT1513438	hsa-miR-3688-3p	CLIP-seq
MIRT1513440	hsa-miR-3915	CLIP-seq
MIRT1513441	hsa-miR-3928	CLIP-seq
MIRT1513442	hsa-miR-4261	CLIP-seq
MIRT1513447	hsa-miR-4457	CLIP-seq
MIRT1513452	hsa-miR-4689	CLIP-seq
MIRT1513459	hsa-miR-513b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	17764085
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	17764085
GO:0001947	Process	Heart looping	IMP	9354794
GO:0003700	Function	DNA-binding transcription factor activity	IDA	17764085
GO:0005515	Function	Protein binding	IPI	17764085, 18716025
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	ISS
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	ISS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0007368	Process	Determination of left/right symmetry	IMP	9354794
GO:0007417	Process	Central nervous system development	IBA	21873635
GO:0009952	Process	Anterior/posterior pattern specification	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0030324	Process	Lung development	IMP	9354794
GO:0035019	Process	Somatic stem cell population maintenance	TAS
GO:0035469	Process	Determination of pancreatic left/right asymmetry	IMP	9354794
GO:0035545	Process	Determination of left/right asymmetry in nervous system	IEA
GO:0043565	Function	Sequence-specific DNA binding	IDA	17764085
GO:0045893	Process	Positive regulation of transcription, DNA-templated	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	17764085
GO:0046872	Function	Metal ion binding	IEA
GO:0071907	Process	Determination of digestive tract left/right asymmetry	IMP	9354794
GO:0071910	Process	Determination of liver left/right asymmetry	IMP	9354794
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 300265
• HGNC: 12874
• e!Ensembl: ENSG00000156925

Protein

• UniProt ID: O60481
• Protein name: Zinc finger protein ZIC 3 (Zinc finger protein 203) (Zinc finger protein of the cerebellum 3)
• Protein function: Acts as a transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.
• PDB: 2EJ4, 2RPC
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18366	zf_ZIC	244 → 290	Zic proteins zinc finger domain	Domain
  PF00096	zf-C2H2	295 → 322	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	328 → 352	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	358 → 382	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	388 → 410	Zinc finger, C2H2 type	Domain

• Sequence:

  MTMLLDGGPQFPGLGVGSFGAPRHHEMPNREPAGMGLNPFGDSTHAAAAAAAAAAFKLSP
  AAAHDLSSGQSSAFTPQGSGYANALGHHHHHHHHHHHTSQVPSYGGAASAAFNSTREFLF
  RQRSSGLSEAASGGGQHGLFAGSASSLHAPAGIPEPPSYLLFPGLHEQGAGHPSPTGHVD
  NNQVHLGLRGELFGRADPYRPVASPRTDPYAAGAQFPNYSPMNMNMGVNVAAHHGPGAFF
  RYMRQPIKQELSCKWIDEAQLSRPKKSCDRTFSTMHELVTHVTMEHVGGPEQNNHVCYWE
  ECPREGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKIFARSENLKIHKRTHTGEKPFKC
  EFEGCDRRFANSSDRKKHMHVHTSDKPYICKVCDKSYTHPSSLRKHMKVHESQGSDSSPA
  ASSGYESSTPPAIASANSKDTTKTPSAVQTSTSHNPGLPPNFNEWYV

• Sequence length: 467

Pathways

KEGG:

Signaling pathways regulating pluripotency of stem cells

Reactome:

POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
Transcriptional regulation of pluripotent stem cells

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Atrial septal defect	Atrial Septal Defects	rs137852951, rs137852953, rs137852955, rs267607106, rs104893900, rs104893901, rs104893903, rs606231358, rs606231359, rs137852683, rs606231360, rs104893907, rs104894073, rs1585703301, rs104894074, rs267606903, rs121912677, rs387906585, rs387906773, rs72554028, rs587782928, rs587782929, rs587782930, rs587784067, rs1555226315, rs879253754, rs1114167356, rs773922431, rs1554093487, rs1554093433, rs1554093461, rs1561621507, rs1561619801, rs766692577, rs1581108237, rs1581111034, rs1579663872, rs1583066622, rs1456289029, rs1761430125
Congenital heart defects	CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 1, X-LINKED	rs267607101, rs121434422, rs387906498, rs397509416, rs587777371, rs587777372, rs587777374, rs367537998, rs797044882, rs886041730, rs768027510, rs1064793873, rs1555447012, rs1554263268, rs1554263321, rs1555223294, rs782051102, rs1555896779, rs1555896778, rs1555897088, rs374016704, rs1555446983, rs1479104927, rs1562443558, rs755445139, rs1581616817, rs1581655293, rs1899172049
Dextrocardia	Dextrocardia	rs1555672928	17127413
Heterotaxia	Heterotaxy Syndrome	rs200321595, rs775946081, rs1060501464, rs1560086701
Heterotaxy, visceral	Heterotaxy, Visceral, 5, Autosomal	rs104893611, rs863223280, rs2144412496, rs375801610, rs528302390, rs878855044, rs145119918, rs886041273, rs137955225, rs1559655653, rs1564667180, rs1564667617, rs1447874899, rs145789868, rs1312300020, rs1564667078, rs1589152470, rs753911740
Heterotaxy, visceral, x-linked	HETEROTAXY, VISCERAL, 1, X-LINKED	rs122462165, rs122462166, rs104894960, rs104894961, rs104894962, rs2124184319, rs122463168, rs886041111, rs1556029841, rs1203069392, rs122463167, rs1569345504, rs1569345742, rs1569345723, rs1602742808, rs1602743059	17764085, 21465648, 9354794, 18716025, 17295247, 14681828, 24123890
Hydrocephalus	Hydrocephalus	rs387907320, rs369384363, rs387907321, rs372127610, rs770273135, rs797045095, rs797045707, rs769795916, rs781251438, rs922703465, rs376078512, rs1567043467, rs1587149916, rs1586841546
Situs inversus	Situs Inversus	rs528302390, rs1596264554
Transposition of great vessels	Transposition of Great Vessels	rs869312707, rs1555246154, rs1565995034, rs1565995146, rs1029377279, rs1565997261, rs1566010195, rs1566005476, rs1870202051
Vacterl association	VACTERL Association With Hydrocephalus	rs752504125, rs869320684, rs776556963	2629409
Vacterl association, x-linked, with or without hydrocephalus	VACTERL ASSOCIATION, X-LINKED, WITH OR WITHOUT HYDROCEPHALUS	rs398122850, rs869320685	20452998, 21465648, 24123890
Ventricular septal defect	Ventricular Septal Defects	rs104894073, rs387906775

Unknown
Disease name	Disease term	dbSNP ID	References
Biliary atresia	Biliary Atresia
Bone disease	Bone Diseases, Developmental		17127413
Ciliopathies	Ciliopathies
Asplenia	Congenital absence of spleen
Hydronephrosis	Hydronephrosis
Imperforate anus	Anus, Imperforate
Isolated congenitally uncorrected transposition of the great arteries	Isolated congenitally uncorrected transposition of the great arteries
Polysplenia	Polysplenia
Pulmonary stenosis	Pulmonary Stenosis
Rectal stenosis	Rectal Stenosis
Renal agenesis	Congenital absence of kidneys syndrome
Sacral agenesis	Sacral agenesis
Situs ambiguus	Situs ambiguus, Situs ambiguous		9354794
Urethral atresia	Urethral atresia