INSM1

INSM transcriptional repressor 1, the group of SNAG transcriptional repressors

Basic information

Region (hg38): 20:20368104-20370949

Links

ENSG00000173404 ∙ NCBI:3642 ∙ OMIM:600010 ∙ HGNC:6090 ∙ Uniprot:Q01101 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the INSM1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INSM1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			38	2		40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	38	2	1

Variants in INSM1

This is a list of pathogenic ClinVar variants found in the INSM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-20368297-C-A		not specified	Uncertain significance (Nov 24, 2024)
20-20368304-T-G		not specified	Uncertain significance (Jul 09, 2021)
20-20368347-A-G		not specified	Uncertain significance (May 05, 2023)
20-20368383-C-T		not specified	Uncertain significance (Mar 27, 2023)
20-20368395-C-T		not specified	Uncertain significance (Feb 23, 2023)
20-20368428-C-A		not specified	Uncertain significance (Dec 02, 2022)
20-20368447-G-A			Benign (Dec 26, 2018)
20-20368502-C-T		not specified	Uncertain significance (Feb 16, 2023)
20-20368505-C-A		not specified	Uncertain significance (Jan 07, 2022)
20-20368506-C-T		not specified	Uncertain significance (Sep 26, 2023)
20-20368511-G-C		not specified	Uncertain significance (Oct 26, 2022)
20-20368526-C-T		not specified	Uncertain significance (Apr 06, 2023)
20-20368557-C-G		not specified	Uncertain significance (Jan 08, 2025)
20-20368574-A-T		not specified	Uncertain significance (Feb 28, 2023)
20-20368686-G-A		not specified	Uncertain significance (Jan 27, 2025)
20-20368689-G-T		not specified	Uncertain significance (Aug 17, 2021)
20-20368739-G-T		not specified	Uncertain significance (Feb 25, 2025)
20-20368743-C-T		not specified	Uncertain significance (Jun 28, 2023)
20-20368776-G-A		not specified	Uncertain significance (Apr 04, 2023)
20-20368776-G-T		not specified	Uncertain significance (Apr 15, 2024)
20-20368796-G-A		not specified	Uncertain significance (Nov 29, 2023)
20-20368827-C-A		not specified	Uncertain significance (Jul 09, 2024)
20-20368827-C-T		not specified	Uncertain significance (Sep 16, 2021)
20-20368862-G-C		not specified	Uncertain significance (Nov 10, 2022)
20-20368872-C-G		not specified	Uncertain significance (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INSM1	protein_coding	protein_coding	ENST00000310227	1	2826

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.269	0.709	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	146	189	0.771	0.00000907	3110
Missense in Polyphen		12	16.083	0.74615		259
Synonymous	-0.335	93	89.0	1.05	0.00000455	1130
Loss of Function	1.92	2	7.78	0.257	3.35e-7	124

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. Binds to the consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target promoters. Acts as a transcriptional repressor of NEUROD1 and INS expression via its interaction with cyclin CCND1 in a cell cycle-independent manner. Negatively regulates skeletal muscle- specific gene expression in endocrine cells of the pituitary by inhibiting the Notch signaling pathway. Represses target gene transcription by recruiting chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and RCOR1 histone deacetylases. Binds to its own promoter, suggesting autoregulation as a self-control feedback mechanism. Promotes the generation and expansion of neuronal basal progenitor cells in the developing neocortex. Involved in the differentiation of endocrine cells of the developing anterior pituitary gland, of the pancreas and intestine, and of sympatho-adrenal cells in the peripheral nervous system. Promotes cell cycle signaling arrest and inhibition of cellular proliferation. {ECO:0000269|PubMed:11842116, ECO:0000269|PubMed:16511571, ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:19124461}.

Haploinsufficiency Scores

• pHI: 0.126
• ghis: 0.605

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.635

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Insm1
• Phenotype: respiratory system 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); digestive/alimentary 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); cellular phenotype; growth/size/body region phenotype; taste/olfaction phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: insm1a
• Affected structure: retinal bipolar neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;negative regulation of protein phosphorylation;type B pancreatic cell differentiation;pancreatic A cell differentiation;type B pancreatic cell development;noradrenergic neuron development;cell cycle;negative regulation of cell population proliferation;regulation of gene expression;positive regulation of cell migration;endocrine pancreas development;norepinephrine biosynthetic process;regulation of protein complex assembly;positive regulation of cell differentiation;transdifferentiation;adrenal chromaffin cell differentiation;sympathetic ganglion development;positive regulation of cell cycle arrest;positive regulation of neural precursor cell proliferation
• Cellular component: nucleus;nucleoplasm;transcriptional repressor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;cyclin binding;chromatin DNA binding;histone deacetylase binding;metal ion binding