SIM2 (SIM bHLH transcription factor 2)

Gene

• Entrez ID: 6493
• Gene name: SIM bHLH transcription factor 2
• Gene symbol: SIM2
• Synonyms (NCBI Gene): HMC13F06, HMC29C01, SIM, bHLHe15
• Chromosome: 21
• Chromosome location: 21q22.13
• Summary: This gene represents a homolog of the Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of neurogenesis. The encoded protein is ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including the park

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT653824	hsa-miR-4762-5p	HITS-CLIP	23824327
MIRT653823	hsa-miR-371b-5p	HITS-CLIP	23824327
MIRT653822	hsa-miR-373-5p	HITS-CLIP	23824327
MIRT653821	hsa-miR-616-5p	HITS-CLIP	23824327
MIRT653820	hsa-miR-371a-5p	HITS-CLIP	23824327
MIRT653819	hsa-miR-372-5p	HITS-CLIP	23824327
MIRT653818	hsa-miR-513c-5p	HITS-CLIP	23824327
MIRT653817	hsa-miR-514b-5p	HITS-CLIP	23824327
MIRT653816	hsa-miR-7641	HITS-CLIP	23824327
MIRT653824	hsa-miR-4762-5p	HITS-CLIP	23824327
MIRT653823	hsa-miR-371b-5p	HITS-CLIP	23824327
MIRT653822	hsa-miR-373-5p	HITS-CLIP	23824327
MIRT653821	hsa-miR-616-5p	HITS-CLIP	23824327
MIRT653820	hsa-miR-371a-5p	HITS-CLIP	23824327
MIRT653819	hsa-miR-372-5p	HITS-CLIP	23824327
MIRT653818	hsa-miR-513c-5p	HITS-CLIP	23824327
MIRT653817	hsa-miR-514b-5p	HITS-CLIP	23824327
MIRT653816	hsa-miR-7641	HITS-CLIP	23824327
MIRT1349424	hsa-miR-205	CLIP-seq
MIRT1349425	hsa-miR-223	CLIP-seq
MIRT1349426	hsa-miR-2278	CLIP-seq
MIRT1349427	hsa-miR-23a	CLIP-seq
MIRT1349428	hsa-miR-23b	CLIP-seq
MIRT1349429	hsa-miR-23c	CLIP-seq
MIRT1349430	hsa-miR-25	CLIP-seq
MIRT1349431	hsa-miR-2964a-3p	CLIP-seq
MIRT1349432	hsa-miR-3186-5p	CLIP-seq
MIRT1349433	hsa-miR-32	CLIP-seq
MIRT1349434	hsa-miR-33a	CLIP-seq
MIRT1349435	hsa-miR-33b	CLIP-seq
MIRT1349436	hsa-miR-363	CLIP-seq
MIRT1349437	hsa-miR-367	CLIP-seq
MIRT1349438	hsa-miR-3944-5p	CLIP-seq
MIRT1349439	hsa-miR-4255	CLIP-seq
MIRT1349440	hsa-miR-4277	CLIP-seq
MIRT1349441	hsa-miR-4289	CLIP-seq
MIRT1349442	hsa-miR-4694-3p	CLIP-seq
MIRT1349443	hsa-miR-4698	CLIP-seq
MIRT1349444	hsa-miR-545	CLIP-seq
MIRT1349445	hsa-miR-548p	CLIP-seq
MIRT1349446	hsa-miR-586	CLIP-seq
MIRT1349447	hsa-miR-642b	CLIP-seq
MIRT1349448	hsa-miR-92a	CLIP-seq
MIRT1349449	hsa-miR-92b	CLIP-seq
MIRT1557022	hsa-miR-744	CLIP-seq
MIRT2103540	hsa-miR-4643	CLIP-seq
MIRT2103541	hsa-miR-466	CLIP-seq
MIRT2103542	hsa-miR-4789-3p	CLIP-seq
MIRT2103543	hsa-miR-125a-3p	CLIP-seq
MIRT2103544	hsa-miR-2117	CLIP-seq
MIRT2103545	hsa-miR-3065-3p	CLIP-seq
MIRT2103546	hsa-miR-3185	CLIP-seq
MIRT2103547	hsa-miR-4273	CLIP-seq
MIRT2103548	hsa-miR-4300	CLIP-seq
MIRT2103549	hsa-miR-4487	CLIP-seq
MIRT2103550	hsa-miR-4717-3p	CLIP-seq
MIRT2103551	hsa-miR-5095	CLIP-seq
MIRT2103552	hsa-miR-552	CLIP-seq
MIRT2103553	hsa-miR-609	CLIP-seq
MIRT2103554	hsa-miR-920	CLIP-seq
MIRT2622801	hsa-miR-1915	CLIP-seq
MIRT1349432	hsa-miR-3186-5p	CLIP-seq
MIRT2622802	hsa-miR-4726-3p	CLIP-seq
MIRT1349447	hsa-miR-642b	CLIP-seq
MIRT2622801	hsa-miR-1915	CLIP-seq
MIRT1349432	hsa-miR-3186-5p	CLIP-seq
MIRT2622802	hsa-miR-4726-3p	CLIP-seq
MIRT1349447	hsa-miR-642b	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
MYB	Unknown	11404025

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	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	8661114
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	8661114, 9199934
GO:0005515	Function	Protein binding	IPI	25036637, 32814053, 35914814
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007399	Process	Nervous system development	IEA
GO:0007399	Process	Nervous system development	TAS	9199934
GO:0009880	Process	Embryonic pattern specification	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0030154	Process	Cell differentiation	IEA
GO:0030324	Process	Lung development	IEA
GO:0045892	Process	Negative regulation of DNA-templated transcription	IEA
GO:0046982	Function	Protein heterodimerization activity	IEA
GO:0046983	Function	Protein dimerization activity	IEA
GO:0048731	Process	System development	IEA

Other IDs

• MIM: 600892
• HGNC: 10883
• e!Ensembl: ENSG00000159263

Protein

• UniProt ID: Q14190
• Protein name: Single-minded homolog 2 (Class E basic helix-loop-helix protein 15) (bHLHe15)
• Protein function: Transcription factor that may be a master gene of CNS development in cooperation with Arnt. It may have pleiotropic effects in the tissues expressed during development.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00989	PAS	79 → 164	PAS fold	Domain
  PF08447	PAS_3	242 → 329	PAS fold	Domain
  PF06621	SIM_C	358 → 660	Single-minded protein C-terminus	Family

• Sequence:

  MKEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRAVFPEGL
  GDAWGQPSRAGPLDGVAKELGSHLLQTLDGFVFVVASDGKIMYISETASVHLGLSQVELT
  GNSIYEYIHPSDHDEMTAVLTAHQPLHHHLLQEYEIERSFFLRMKCVLAKRNAGLTCSGY
  KVIHCSGYLKIRQYMLDMSLYDSCYQIVGLVAVGQSLPPSAITEIKLYSNMFMFRASLDL
  KLIFLDSRVTEVTGYEPQDLIEKTLYHHVHGCDVFHLRYAHHLLLVKGQVTTKYYRLLSK
  RGGWVWVQSYATVVHNSRSSRPHCIVSVNYVLTEIEYKELQLSLEQVSTAKSQDSWRTAL
  STSQETRKLVKPKNTKMKTKLRTNPYPPQQYSSFQMDKLECGQLGNWRASPPASAAAPPE
  LQPHSESSDLLYTPSYSLPFSYHYGHFPLDSHVFSSKKPMLPAKFGQPQGSPCEVARFFL
  STLPASGECQWHYANPLVPSSSSPAKNPPEPPANTARHSLVPSYEAPAAAVRRFGEDTAP
  PSFPSCGHYREEPALGPAKAARQAARDGARLALARAAPECCAPPTPEAPGAPAQLPFVLL
  NYHRVLARRGPLGGAAPAASGLACAPGGPEAATGALRLRHPSPAATSPPGAPLPHYLGAS
  VIITNGR

• Sequence length: 667

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
Neurodevelopmental with craniofacial anomalies disorder	Likely pathogenic	rs201840539	RCV001816027	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLEFT PALATE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOFACIAL ABNORMALITIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEASONAL ALLERGIC RHINITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TESTICULAR CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adrenal Gland Pheochromocytoma	Adrenal Gland Pheochromocytoma	BEFREE	7952399		★☆☆☆☆ Found in Text Mining only
Benign Prostatic Hyperplasia	Benign Prostatic Hyperplasia	BEFREE	12530058		★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain Neoplasms	BEFREE	20448453		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	16840439, 19169276, 31775907, 31783895		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	37121978	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	33650646	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	12676991		★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	29109451	Associate	★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	12676991, 16129820		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	BEFREE	12530058, 16129820		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	16129820	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	27497007, 29964097		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	10400987, 10915774, 12174971, 12676991, 14701734, 15068251, 16840439, 22048266, 22660985, 23343470, 25319570, 7485157, 8661114, 8661115, 9199934		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	LHGDN	15946822		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	16129820, 20448453, 22048266, 23343470, 7485157	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	33650646	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	20448453		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	20448453		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	24162743, 24909296		★☆☆☆☆ Found in Text Mining only
Hirschsprung Disease	Hirschsprung Disease	BEFREE	20977903		★☆☆☆☆ Found in Text Mining only
Holoprosencephaly	Holoprosencephaly	BEFREE	7485157		★☆☆☆☆ Found in Text Mining only
Holoprosencephaly	Holoprosencephaly	Pubtator	7485157	Associate	★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	BEFREE	30050930		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	10400987, 14701734		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	LHGDN	15946822		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	28450913		★☆☆☆☆ Found in Text Mining only
Invasive Ductal Breast Carcinoma	Invasive Duct and Lobular Carcinoma	BEFREE	30531838		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	28768794		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28192239		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	16840439, 19169276, 31775907, 31783895		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	12676991		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	14550949		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	19737960, 22174909, 24690990, 28910345		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	12530058, 12676991, 19668230, 20448453, 22174909, 23343470, 24690990, 25501803		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	12676991		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	16840439, 18160708, 22777354		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	16840439, 18160708		★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	BEFREE	31276963		★☆☆☆☆ Found in Text Mining only
Mental Retardation	Mental retardation	BEFREE	10400987, 14701734		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	25501803		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	16129820, 19169276, 22777354, 24162743, 24909296, 28332364, 29109451, 29427302, 31783895		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	28332364		★☆☆☆☆ Found in Text Mining only
Noninfiltrating Intraductal Carcinoma	Ductal carcinoma	BEFREE	22777354, 30531838		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35370009	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	14550949, 19668230		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	38477085	Associate	★☆☆☆☆ Found in Text Mining only
Pheochromocytoma	Pheochromocytoma	BEFREE	7952399		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	19737960, 22174909, 24690990, 28910345		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Hyperplasia	Prostatic Hyperplasia	LHGDN	12530058		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	19668230, 20448453, 22174909		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	21703393, 22174909, 26364608, 28910345	Associate	★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	BEFREE	29241922		★☆☆☆☆ Found in Text Mining only