SIM1 (SIM bHLH transcription factor 1)

Gene

• Entrez ID: 6492
• Gene name: SIM bHLH transcription factor 1
• Gene symbol: SIM1
• Synonyms (NCBI Gene): bHLHe14
• Chromosome: 6
• Chromosome location: 6q16.3
• Summary: SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. SIM1 transcript was detected only in fetal kidney out of various adult and fetal tissues tested. Since the sim gene plays an important role in Drosophila development and has peak leve

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs145361258	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs1064795024	T>C	Likely-pathogenic	Downstream transcript variant, genic downstream transcript variant, coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	23824327
MIRT636240	hsa-miR-3152-3p	HITS-CLIP	23824327
MIRT636239	hsa-miR-374a-5p	HITS-CLIP	23824327
MIRT636238	hsa-miR-374b-5p	HITS-CLIP	23824327
MIRT636237	hsa-miR-4455	HITS-CLIP	23824327
MIRT636236	hsa-miR-574-5p	HITS-CLIP	23824327
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	23824327
MIRT636240	hsa-miR-3152-3p	HITS-CLIP	23824327
MIRT636239	hsa-miR-374a-5p	HITS-CLIP	23824327
MIRT636238	hsa-miR-374b-5p	HITS-CLIP	23824327
MIRT636237	hsa-miR-4455	HITS-CLIP	23824327
MIRT636236	hsa-miR-574-5p	HITS-CLIP	23824327
MIRT636240	hsa-miR-3152-3p	HITS-CLIP	27418678
MIRT636240	hsa-miR-3152-3p	HITS-CLIP	27418678
MIRT636240	hsa-miR-3152-3p	HITS-CLIP	27418678
MIRT636239	hsa-miR-374a-5p	HITS-CLIP	27418678
MIRT636239	hsa-miR-374a-5p	HITS-CLIP	27418678
MIRT636239	hsa-miR-374a-5p	HITS-CLIP	27418678
MIRT636238	hsa-miR-374b-5p	HITS-CLIP	27418678
MIRT636238	hsa-miR-374b-5p	HITS-CLIP	27418678
MIRT636238	hsa-miR-374b-5p	HITS-CLIP	27418678
MIRT636237	hsa-miR-4455	HITS-CLIP	27418678
MIRT636237	hsa-miR-4455	HITS-CLIP	27418678
MIRT636237	hsa-miR-4455	HITS-CLIP	27418678
MIRT636237	hsa-miR-4455	HITS-CLIP	27418678
MIRT636236	hsa-miR-574-5p	HITS-CLIP	27418678
MIRT636236	hsa-miR-574-5p	HITS-CLIP	27418678
MIRT636236	hsa-miR-574-5p	HITS-CLIP	27418678
MIRT636236	hsa-miR-574-5p	HITS-CLIP	27418678
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	27418678
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	27418678
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	27418678
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	27418678
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	23824327
MIRT636240	hsa-miR-3152-3p	HITS-CLIP	23824327
MIRT636239	hsa-miR-374a-5p	HITS-CLIP	23824327
MIRT636238	hsa-miR-374b-5p	HITS-CLIP	23824327
MIRT636237	hsa-miR-4455	HITS-CLIP	23824327
MIRT636236	hsa-miR-574-5p	HITS-CLIP	23824327
MIRT636241	hsa-miR-6867-5p	HITS-CLIP	23824327
MIRT636240	hsa-miR-3152-3p	HITS-CLIP	23824327
MIRT636239	hsa-miR-374a-5p	HITS-CLIP	23824327
MIRT636238	hsa-miR-374b-5p	HITS-CLIP	23824327
MIRT636237	hsa-miR-4455	HITS-CLIP	23824327
MIRT636236	hsa-miR-574-5p	HITS-CLIP	23824327
MIRT1349419	hsa-miR-1271	CLIP-seq
MIRT1349420	hsa-miR-218	CLIP-seq
MIRT1349421	hsa-miR-455-5p	CLIP-seq
MIRT1349422	hsa-miR-636	CLIP-seq
MIRT1349423	hsa-miR-96	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
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:0001657	Process	Ureteric bud development	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	8812055
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	8812055, 9199934
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
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:0030154	Process	Cell differentiation	IEA
GO:0046982	Function	Protein heterodimerization activity	IEA
GO:0046982	Function	Protein heterodimerization activity	ISS
GO:0046983	Function	Protein dimerization activity	IEA
GO:0048731	Process	System development	IEA

Other IDs

• MIM: 603128
• HGNC: 10882
• e!Ensembl: ENSG00000112246

Protein

• UniProt ID: P81133
• Protein name: Single-minded homolog 1 (Class E basic helix-loop-helix protein 14) (bHLHe14)
• Protein function: Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00010	HLH	2 → 52	Helix-loop-helix DNA-binding domain	Domain
  PF00989	PAS	79 → 167	PAS fold	Domain
  PF08447	PAS_3	242 → 329	PAS fold	Domain
  PF06621	SIM_C	359 → 669	Single-minded protein C-terminus	Family

• Sequence:

  MKEKSKNAARTRREKENSEFYELAKLLPLPSAITSQLDKASIIRLTTSYLKMRVVFPEGL
  GEAWGHSSRTSPLDNVGRELGSHLLQTLDGFIFVVAPDGKIMYISETASVHLGLSQVELT
  GNSIYEYIHPADHDEMTAVLTAHQPYHSHFVQEYEIERSFFLRMKCVLAKRNAGLTCGGY
  KVIHCSGYLKIRQYSLDMSPFDGCYQNVGLVAVGHSLPPSAVTEIKLHSNMFMFRASLDM
  KLIFLDSRVAELTGYEPQDLIEKTLYHHVHGCDTFHLRCAHHLLLVKGQVTTKYYRFLAK
  HGGWVWVQSYATIVHNSRSSRPHCIVSVNYVLTDTEYKGLQLSLDQISASKPAFSYTSSS
  TPTMTDNRKGAKSRLSSSKSKSRTSPYPQYSGFHTERSESDHDSQWGGSPLTDTASPQLL
  DPADRPGSQHDASCAYRQFSDRSSLCYGFALDHSRLVEERHFHTQACEGGRCEAGRYFLG
  TPQAGREPWWGSRAALPLTKASPESREAYENSMPHIASVHRIHGRGHWDEDSVVSSPDPG
  SASESGDRYRTEQYQSSPHEPSKIETLIRATQQMIKEEENRLQLRKAPSDQLASINGAGK
  KHSLCFANYQQPPPTGEVCHGSALANTSPCDHIQQREGKMLSPHENDYDNSPTALSRISS
  PNSDRISKSSLILAKDYLHSDISPHQTAGDHPTVSPNCFGSHRQYFDKHAYTLTGYALEH
  LYDSETIRNYSLGCNGSHFDVTSHLRMQPDPAQGHKGTSVIITNGS

• Sequence length: 766

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
Brachydactyly	Likely pathogenic	rs1057518333	RCV001249456	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Obesity due to SIM1 deficiency	Pathogenic	rs2114540946	RCV002273359	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SIM1-associated metabolic syndrome	Likely pathogenic	rs2482134518	RCV002468461	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SIM1-related disorder	Likely pathogenic	rs772202157	RCV001269255	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC VENOUS INSUFFICIENCY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLEX NEURODEVELOPMENTAL DISORDER	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ERECTILE DYSFUNCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART FAILURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERGLYCEMIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IRRITABLE BOWEL SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL OR BEHAVIOURAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Monogenic diabetes	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OBESITY DUE TO SIM BHLH TRANSCRIPTION FACTOR 1 DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity with Prader-Willi like phenotype	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Oromandibular-limb hypogenesis spectrum	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSYCHIATRIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schaaf-Yang syndrome	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SIM1-related obesity	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
6q16 microdeletion syndrome	6q16 microdeletion syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	27782156		★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachycephaly	Brachycephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	CTD_human_DG	15818620		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	30218172		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	39201344	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
cervical cancer	Cervical Cancer	BEFREE	29063719		★☆☆☆☆ Found in Text Mining only
Cervix carcinoma	Cervix carcinoma	BEFREE	29063719		★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	25234154	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital fusion of ribs	Rib fusion	BEFREE	30801883		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	31813757		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	25234154	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Insipidus	Diabetes insipidus	Pubtator	40428410	Associate	★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	9199934		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Erectile dysfunction	Erectile Dysfunction	BEFREE	30583798		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fatty Liver	Fatty liver	Pubtator	40428410	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	23401328, 25234154		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	Pubtator	40428410	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	CTD_human_DG	18056790		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperglycemia	Hyperglycemia	BEFREE	30698681		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperinsulinism	Hyperinsulinism	Pubtator	40428410	Associate	★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	BEFREE	24038875		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	23401328		★☆☆☆☆ Found in Text Mining only
Language Disorders	Language Disorders	BEFREE	24635660		★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macrotia	Macrotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	CTD_human_DG	15818620		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30218172		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29063719		★☆☆☆☆ Found in Text Mining only
Malignant tumor of cervix	Cervical Tumor	BEFREE	29063719		★☆☆☆☆ Found in Text Mining only
Mammary Carcinoma, Human	Marfan Syndrome	CTD_human_DG	15818620		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	CTD_human_DG	15818620		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms, Human	Mammary Neoplasms	CTD_human_DG	15818620		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	31813757		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Monoclonal B-Cell Lymphocytosis	B-Cell Lymphocytosis	BEFREE	23143900		★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29063719		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	10587584, 16709610, 16829351, 16924270, 18648397, 19401419, 20075856, 23401328, 23778136, 23778139, 24038875, 24097297, 24203700, 25234154, 25351778, 28472148, 28593922, 29066024, 29216354, 30615192		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Obesity	Obesity	GENOMICS_ENGLAND_DG	16924270		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Obesity	Obesity	Pubtator	19401419, 20075856, 21512513, 23778136, 23778139, 25234154, 25351778, 30991789, 37329217, 40428410	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Obesity	Obesity	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Obesity due to SIM1 deficiency	Obesity	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Obesity, Morbid	Obesity	BEFREE	10587584, 21512513, 23778136, 24097297, 24203700, 25234154, 28472148		★☆☆☆☆ Found in Text Mining only
Prader-Willi Syndrome	Prader-Willi Syndrome	BEFREE	23401328, 24038875		★☆☆☆☆ Found in Text Mining only
Prader-Willi-like syndrome	Prader-Willi-Like Syndrome	BEFREE	23778136, 24038875		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	23778139	Inhibit	★☆☆☆☆ Found in Text Mining only
SIM1-related Prader-Willi-like syndrome	Prader-Willi-Like Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of lung	Lung carcinoma	BEFREE	31710242		★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only