INSC

protein-coding

INSC spindle orientation adaptor protein, the group of Armadillo like helical domain containing

Gene summary

In Drosophila, neuroblasts divide asymmetrically into another neuroblast at the apical side and a smaller ganglion mother cell on the basal side. Cell polarization is precisely regulated by 2 apically localized multiprotein signaling complexes that are tethered by Inscuteable, which regulates their apical localization (Izaki et al., 2006 [PubMed 16458856]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001042536.3

Inheritance

—

ClinVar variants

U:99B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr11:15,112,424-15,247,208

External References & Databases

Ensembl (ENSG00000188487)

Transcript & Mutation Effects

hg38 • Region Span ~134.8 kb

Loading mutation effect viewer...

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 INSC variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001042536.3. 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			2 clinvar	1 clinvar		3
missense			96 clinvar	4 clinvar	1 clinvar	101
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	99	5	1	105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001042536.3	RefSeq	NP_001036001.1	12	MANE Select
ENST00000379556.8	Ensembl	ENSP00000368874.3	12	MANE Select
NM_001031853.5	RefSeq	NP_001027024.3	13	Standard
NM_001278313.2	RefSeq	NP_001265242.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nervous system development
asymmetric cell division
cell differentiation
regulation of protein stability

Molecular Function

protein binding
protein domain specific binding
protein binding, bridging

Cellular Component

plasma membrane
cell cortex
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379554
Coding exons: 13
Length: 134785
Individuals with no LoFs: 125110
Homozygous LoFs: 1
Heterozygous LoFs: 240
Defined: 125351
p: 0.000962

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.190	358	348	1.03	0.0000211	3722
Missense (PolyPhen)		123	116.78	1.0533		1234
Synonymous	0.611	132	141	0.935	0.00000864	1182
Loss of Function	0.203	28	29.2	0.959	0.00000150	318

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0049	0.0046	notable
Latino/Admixed American	0.00067	0.00067	rare
Ashkenazi Jewish	0.0038	0.0038	notable
East Asian	0.00073	0.00072	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00061	0.00060	rare
South Asian	0.00062	0.00059	rare
Other	0.0010	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as an adapter linking the Par3 complex to the GPSM1/GPSM2 complex (PubMed:16458856). Involved in spindle orientation during mitosis. May regulate cell proliferation and differentiation in the developing nervous system. May play a role in the asymmetric division of fibroblasts and participate in the process of stratification of the squamous epithelium (By similarity). {ECO:0000250|UniProtKB:Q3HNM7, ECO:0000305|PubMed:16458856}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.929
RVIS EVS: 0.89
RVIS percentile EVS: 89.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.141

Gene Damage Prediction

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