SIX2 (SIX homeobox 2)

Gene

• Entrez ID: 10736
• Gene name: SIX homeobox 2
• Gene symbol: SIX2
• Synonyms: -
• Chromosome: 2
• Chromosome location: 2p21
• Summary: This gene is a member of the vertebrate gene family which encode proteins homologous to the Drosophila `sine oculis` homeobox protein. The encoded protein is a transcription factor which, like other members of this gene family, may be involved in limb or

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs756635283	C>A,T	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT438371	hsa-miR-181b-5p	Luciferase reporter assay, qRT-PCR, Western blot	24055707
MIRT438371	hsa-miR-181b-5p	Luciferase reporter assay, qRT-PCR, Western blot	24055707
MIRT438371	hsa-miR-181b-5p	Luciferase reporter assay, qRT-PCR, Western blot	24055707
MIRT438371	hsa-miR-181b-5p	Luciferase reporter assay, qRT-PCR, Western blot	24055707
MIRT1350379	hsa-miR-185	CLIP-seq
MIRT1350380	hsa-miR-4306	CLIP-seq
MIRT1350381	hsa-miR-4419a	CLIP-seq
MIRT1350382	hsa-miR-4510	CLIP-seq
MIRT1350383	hsa-miR-4644	CLIP-seq
MIRT2103832	hsa-miR-3150b-3p	CLIP-seq
MIRT2103833	hsa-miR-4433	CLIP-seq
MIRT2103834	hsa-miR-4459	CLIP-seq
MIRT2103835	hsa-miR-4768-3p	CLIP-seq
MIRT2103836	hsa-miR-4784	CLIP-seq
MIRT2103837	hsa-miR-765	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0001822	Process	Kidney development	IBA	21873635
GO:0001822	Process	Kidney development	IMP	18305125
GO:0001822	Process	Kidney development	ISS
GO:0002062	Process	Chondrocyte differentiation	IEA
GO:0003337	Process	Mesenchymal to epithelial transition involved in metanephros morphogenesis	ISS
GO:0003700	Function	DNA-binding transcription factor activity	NAS	10773454
GO:0005515	Function	Protein binding	IPI	30894749, 32296183
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005667	Component	Transcription regulator complex	IBA	21873635
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006606	Process	Protein import into nucleus	IEA
GO:0007501	Process	Mesodermal cell fate specification	ISS
GO:0008134	Function	Transcription factor binding	IEA
GO:0008283	Process	Cell population proliferation	IDA	22995329
GO:0009653	Process	Anatomical structure morphogenesis	TAS	10773454
GO:0009948	Process	Anterior/posterior axis specification	ISS
GO:0016477	Process	Cell migration	IDA	22995329
GO:0030278	Process	Regulation of ossification	IEA
GO:0032330	Process	Regulation of chondrocyte differentiation	IEA
GO:0042474	Process	Middle ear morphogenesis	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045596	Process	Negative regulation of cell differentiation	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048557	Process	Embryonic digestive tract morphogenesis	ISS
GO:0048701	Process	Embryonic cranial skeleton morphogenesis	IEA
GO:0072006	Process	Nephron development	ISS
GO:0072028	Process	Nephron morphogenesis	ISS
GO:0072038	Process	Mesenchymal stem cell maintenance involved in nephron morphogenesis	ISS
GO:0072137	Process	Condensed mesenchymal cell proliferation	IEA
GO:0072161	Process	Mesenchymal cell differentiation involved in kidney development	ISS
GO:0090189	Process	Regulation of branching involved in ureteric bud morphogenesis	ISS
GO:0097168	Process	Mesenchymal stem cell proliferation	ISS
GO:1902732	Process	Positive regulation of chondrocyte proliferation	ISS
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 604994
• HGNC: 10888
• e!Ensembl: ENSG00000170577

Protein

• UniProt ID: Q9NPC8
• Protein name: Homeobox protein SIX2 (Sine oculis homeobox homolog 2)
• Protein function: Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16878	SIX1_SD	9 → 119	Transcriptional regulator, SIX1, N-terminal SD domain	Domain
  PF00046	Homeodomain	127 → 181	Homeodomain	Domain

• Sequence:

  MSMLPTFGFTQEQVACVCEVLQQGGNIERLGRFLWSLPACEHLHKNESVLKAKAVVAFHR
  GNFRELYKILESHQFSPHNHAKLQQLWLKAHYIEAEKLRGRPLGAVGKYRVRRKFPLPRS
  IWDGEETSYCFKEKSRSVLREWYAHNPYPSPREKRELAEATGLTTTQVSNWFKNRRQRDR
  AAEAKERENNENSNSNSHNPLNGSGKSVLGSSEDEKTPSGTPDHSSSSPALLLSPPPPGL
  PSLHSLGHPPGPSAVPVPVPGGGGADPLQHHHGLQDSILNPMSANLVDLGS

• Sequence length: 291

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Amyotrophic lateral sclerosis	Amyotrophic Lateral Sclerosis, Familial	rs267607084, rs312262720, rs312262752, rs121908287, rs121908288, rs29001584, rs28941475, rs121434378, rs386134173, rs386134174, rs80356730, rs80356727, rs4884357, rs80356717, rs80356733, rs80356731, rs80356726, rs267606928, rs267606929, rs1885090126, rs121434591, rs121912431, rs121912432, rs121912433, rs121912434, rs121912435, rs121912440, rs121912436, rs121912437, rs121912438, rs121912439, rs74315452, rs121912442, rs121912443, rs121912444, rs121912446, rs121912447, rs1197141604, rs121912448, rs121912449, rs121912450, rs121912451, rs121912452, rs121912453, rs121912454, rs369600566, rs121912455, rs121912456, rs121912457, rs121912458, rs1555836889, rs121909667, rs121909668, rs121909669, rs121909671, rs121909535, rs121909537, rs121909538, rs121909539, rs121909540, rs121909542, rs121909544, rs80356734, rs367543041, rs80356740, rs80356719, rs80356721, rs80356723, rs80356725, rs387906627, rs387906628, rs387906709, rs387906710, rs387906711, rs387906829, rs387907264, rs387907265, rs387907266, rs312262739, rs312262709, rs312262749, rs200793464, rs147713329, rs312262788, rs397514262, rs63751180, rs587777132, rs730880025, rs730880026, rs730880027, rs368743618, rs730880029, rs730882255, rs730882256, rs786205611, rs121912441, rs199947197, rs780136067, rs772731615, rs879253926, rs879254294, rs764717219, rs886041390, rs750159428, rs753207473, rs267607087, rs767350733, rs778305085, rs1554707680, rs1554707622, rs1393363759, rs750959420, rs1555509569, rs1554716504, rs11556620, rs1247392012, rs142083484, rs140385286, rs749428135, rs371575563, rs1402429085, rs1218712729, rs1555179091, rs1555179087, rs746971952, rs1555836950, rs368276916, rs140376902, rs747220413, rs76731700, rs770684782, rs1200906022, rs1804449, rs1482760341, rs769898852, rs140599944, rs757972700, rs1555451521, rs1592362719, rs1555836803, rs763455928, rs1378590183, rs1583695322, rs1362178149, rs1197928094, rs368751524, rs1555509609, rs1574787779, rs1601157750, rs1301635320, rs1341055534, rs1402092579, rs1568809172, rs1555836170, rs1315541036, rs1339283341, rs1643659556, rs1644506661, rs1435710212, rs1553122918, rs1689580631, rs374047961, rs775935265, rs2076486420, rs1820836522, rs757260058, rs1844420892, rs1833371664, rs1833438306, rs1833451208, rs2083790483, rs1303294230, rs1226110412, rs2053207945, rs2053208751, rs2053501632, rs2053539304, rs1567479067, rs544088874, rs1228194239, rs1568807400, rs1169198442, rs2049594204, rs2049594311, rs1568810641, rs1568811372, rs2049618449, rs1476760624, rs2079347087	11796754
Congenital anomalies of kidney and urinary tract	Cakut	rs267606865, rs121908436, rs281875326, rs879255515, rs75462234, rs869320679, rs760905589, rs797045022, rs869320624, rs745597204, rs1114167358, rs1555879360, rs1577330805, rs1008555507	24429398
Kidney disease	Kidney Diseases	rs74315342, rs749740335, rs757649673, rs112417755, rs35138315	18570229
Lateral sclerosis	AMYOTROPHIC LATERAL SCLEROSIS 1, Amyotrophic Lateral Sclerosis, Sporadic	rs386134181, rs386134176, rs386134174, rs386134184, rs386134178, rs1693780539, rs1574698048	11796754
Macrocephaly	Macrocephaly	rs786204854, rs764333096, rs1557739557
Nephroblastoma	Nephroblastoma	rs1553551874, rs1555913934, rs769116796	28825729
Wilms tumor	Bilateral Wilms Tumor	rs121918261, rs2116574924, rs587776573, rs587776574, rs121907900, rs121907901, rs587776576, rs121907909, rs121907906, rs587776577, rs121907911, rs80359604, rs80358785, rs104894855, rs122453119, rs122453121, rs869025310, rs869025311, rs869025312, rs121907903, rs1131690795, rs1554945033, rs1423753702, rs1556297749, rs1569392947, rs1569408743, rs1603240717, rs1602581162, rs771527206, rs2071072322	28825729

Unknown
Disease name	Disease term	dbSNP ID	References
Dwarfism	Dwarfism
Frontal bossing	Frontal bossing
Frontonasal dysplasia	SIX2-related frontonasal dysplasia
Metopic synostosis	Metopic synostosis
Posteriorly rotated ear	Posteriorly rotated ear
Ptosis	Blepharoptosis, Ptosis	rs139920573