INSM1

protein-coding

INSM transcriptional repressor 1, the group of SNAG transcriptional repressors

Gene summary

Insulinoma-associated 1 (INSM1) gene is intronless and encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. This gene is a sensitive marker for neuroendocrine differentiation of human lung tumors. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002196.3

Inheritance

—

ClinVar variants

U:72B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr20:20,368,104-20,370,949

External References & Databases

Ensembl (ENSG00000173404)

Transcript & Mutation Effects

hg38 • Region Span ~2.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INSM1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002196.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			72 clinvar	2 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	72	2	1	75

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002196.3	RefSeq	NP_002187.1	1	MANE Select
ENST00000310227.3	Ensembl	ENSP00000312631.1	1	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
insm1a	Danio rerio	Structure: retinal bipolar neuron Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

insm1a

Danio rerio

Structure: retinal bipolar neuron

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

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

Cellular Component

nucleus
nucleoplasm
transcriptional repressor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310227
Coding exons: 1
Length: 2826
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.12	146	189	0.771	0.00000907	3110
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.635

Gene Damage Prediction

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