SIM1

SIM bHLH transcription factor 1, the group of PAS domain containing|Basic helix-loop-helix proteins

Basic information

Region (hg38): 6:100385009-100464921

Links

ENSG00000112246 ∙ NCBI:6492 ∙ OMIM:603128 ∙ HGNC:10882 ∙ Uniprot:P81133 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• obesity due to SIM1 deficiency (Supportive), mode of inheritance: AR
• complex neurodevelopmental disorder (Strong), mode of inheritance: AD
• obesity due to SIM1 deficiency (Definitive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIM1 gene.

• SIM1-related_disorder (203 variants)
• not_provided (136 variants)
• Inborn_genetic_diseases (84 variants)
• Obesity_due_to_SIM1_deficiency (39 variants)
• not_specified (13 variants)
• Monogenic_diabetes (7 variants)
• SIM1-associated_metabolic_syndrome (3 variants)
• Oromandibular-limb_hypogenesis_spectrum (2 variants)
• Obesity (1 variants)
• Microcephaly (1 variants)
• See_cases (1 variants)
• Obesity_with_Prader-Willi_like_phenotype (1 variants)
• Schaaf-Yang_syndrome (1 variants)
• SIM1-related_obesity (1 variants)
• Brachydactyly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005068.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	85	4	99
missense		1	230	14	1	246
nonsense	1	4	4			9
start loss						0
frameshift	2	1	3			6
splice donor/acceptor (+/-2bp)		1				1
Total	3	7	247	99	5

Highest pathogenic variant AF is 0.0000068150616

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIM1	protein_coding	protein_coding	ENST00000369208	11	79915

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00172	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.715	405	448	0.905	0.0000235	5015
Missense in Polyphen		129	174.87	0.73771		1996
Synonymous	-0.308	194	189	1.03	0.0000110	1511
Loss of Function	4.96	4	36.2	0.111	0.00000192	407

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000879	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult.

Recessive Scores

• pRec: 0.171

Intolerance Scores

• loftool: 0.300
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.88

Haploinsufficiency Scores

• pHI: 0.861
• hipred: Y
• hipred_score: 0.875
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.686

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sim1
• Phenotype: renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: sim1a
• Affected structure: dopaminergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: ureteric bud development;regulation of transcription by RNA polymerase II;nervous system development;cell differentiation
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein heterodimerization activity