SIM1 SIM bHLH transcription factor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SIM1provided by HGNC
Official Full Name: SIM bHLH transcription factor 1provided by HGNC
Primary source: HGNC:HGNC:10882
See related: Ensembl:ENSG00000112246 MIM:603128; AllianceGenome:HGNC:10882
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: bHLHe14
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 levels of expression during the period of neurogenesis,it was proposed that the human SIM gene is a candidate for involvement in certain dysmorphic features (particularly the facial and skull characteristics), abnormalities of brain development, and/or cognitive disability of Down syndrome. [provided by RefSeq, Jul 2008]
Expression: Biased expression in kidney (RPKM 6.6) and fat (RPKM 0.4) See more
Orthologs: mouse all
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Genomic context

Location:: 6q16.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (100385009..100464921, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (101558767..101638670, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (100832885..100912797, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

STIM1/SOX2 proteins are co-expressed in the tumor and microenvironmental stromal cells of pancreatic ductal adenocarcinoma and ampullary carcinoma.
Title: STIM1/SOX2 proteins are co-expressed in the tumor and microenvironmental stromal cells of pancreatic ductal adenocarcinoma and ampullary carcinoma.
Structural Models for the Dynamic Effects of Loss-of-Function Variants in the Human SIM1 Protein Transcriptional Activation Domain.
Title: Structural Models for the Dynamic Effects of Loss-of-Function Variants in the Human SIM1 Protein Transcriptional Activation Domain.
SIM1 is part of the leptin-melanocortin system.
Title: Genetic variation in the SIM1 locus is associated with erectile dysfunction.
SIM1 was highly methylated in the majority of the cervical cancer tissues. Hypermethylation of SIM1 led to a pronounced reduction in SIM1 expression in cervical cancer tissues compared with normal cervix. The degree of SIM1 methylation was significantly associated with the severity of the disease.
Title: Aberrant single-minded homolog 1 methylation as a potential biomarker for cervical cancer.
Single nucleotide polymorphism rs3734354 in SIM1 gene is associated with severe early-onset obesity.
Title: Copy number variations in "classical" obesity candidate genes are not frequently associated with severe early-onset obesity in children.
identified a novel SIM1 variant, p.D134N, in 4 obese individuals from a single pedigree which is also associated with lower preference for certain foods
Title: Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents.
no gene harboring deletions were identified in the SIM1 and MRAP2 regions in the Prader Willi like (PWL) cohort; further functional analysis of p.P352S found in SIM1 and p.A40S found in MRAP2 is useful; this would provide further support for possible role of SIM1 and MRAP2 in the pathogenesis of the PWL phenotype in a limited number of patients
Title: Copy number variation (CNV) analysis and mutation analysis of the 6q14.1-6q16.3 genes SIM1 and MRAP2 in Prader Willi like patients.
Genotype-phenotype correlations confirmed the major role for SIM1 haploinsufficiency in obesity and the Prader-Willi-like phenotype
Title: Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1.
Aberrant DNA methylation of the DLX4 and SIM1 genes may be a novel progression marker for uterine cervical low-grade squamous intraepithelial lesions.
Title: Aberrant DNA methylation of DLX4 and SIM1 is a predictive marker for disease progression of uterine cervical low-grade squamous intraepithelial lesion.
Severe loss-of-function SIM1 mutations can be associated with a spectrum of developmental delay phenotypes and obesity.
Title: Identification of two novel loss-of-function SIM1 mutations in two overweight children with developmental delay.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-04-25) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-04-25) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH120490 (e-PCR)
- UniSTS:133655

PMC34708P3 (e-PCR)
- UniSTS:273236

SHGC-143334 (e-PCR)
- UniSTS:171863

AL022494 (e-PCR)
- UniSTS:52874

PMC310662P1 (e-PCR)
- UniSTS:272626

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in ureteric bud development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: single-minded homolog 1

Names: class E basic helix-loop-helix protein 14; single-minded family bHLH transcription factor 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008230.2 RefSeqGene

Range

5000..84912

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001374769.1 → NP_001361698.1 single-minded homolog 1

Status: REVIEWED

Source sequence(s)

AL121948, Z86062

Consensus CDS

CCDS5045.1

UniProtKB/Swiss-Prot

P81133, Q5TDP7

Related

ENSP00000262901.4, ENST00000262901.4

Conserved Domains (4) summary

cd00130
Location:88 → 158

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam06621
Location:360 → 669

SIM_C; Single-minded protein C-terminus

pfam08447
Location:243 → 329

PAS_3; PAS fold

cd19738
Location:1 → 71

bHLH-PAS_SIM1; basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded homolog 1 (SIM1) and similar proteins
NM_005068.3 → NP_005059.2 single-minded homolog 1

See identical proteins and their annotated locations for NP_005059.2

Status: REVIEWED

Source sequence(s)

AL121948, Z86062

Consensus CDS

CCDS5045.1

UniProtKB/Swiss-Prot

P81133, Q5TDP7

Related

ENSP00000358210.4, ENST00000369208.8

Conserved Domains (4) summary

cd00130
Location:88 → 158

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam06621
Location:360 → 669

SIM_C; Single-minded protein C-terminus

pfam08447
Location:243 → 329

PAS_3; PAS fold

cd19738
Location:1 → 71

bHLH-PAS_SIM1; basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded homolog 1 (SIM1) and similar proteins