NISCH

nischarin

Basic information

Region (hg38): 3:52455117-52493068

Links

ENSG00000010322 ∙ NCBI:11188 ∙ OMIM:615507 ∙ HGNC:18006 ∙ Uniprot:Q9Y2I1 ∙ 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 NISCH gene.

• Inborn genetic diseases (50 variants)
• not provided (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NISCH 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				5	4	9
missense			47	4	4	55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	47	9	8

Variants in NISCH

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

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

Position	Type	Phenotype	Significance	ClinVar
3-52455654-C-G		not specified	Uncertain significance (May 11, 2022)
3-52455661-T-C		not specified	Uncertain significance (Nov 17, 2022)
3-52455693-G-A		not specified	Uncertain significance (Jan 17, 2024)
3-52458800-G-A		not specified	Uncertain significance (Feb 14, 2023)
3-52458843-A-G		not specified	Uncertain significance (Apr 07, 2022)
3-52470861-G-T		not specified	Uncertain significance (Nov 19, 2022)
3-52470877-G-A		not specified	Uncertain significance (Feb 07, 2023)
3-52471848-C-T			Likely benign (Jan 09, 2018)
3-52471936-G-A		not specified	Uncertain significance (Jun 26, 2023)
3-52472349-A-G		not specified	Uncertain significance (Jan 08, 2024)
3-52472351-C-T		not specified	Uncertain significance (Dec 19, 2022)
3-52472358-C-T		not specified	Uncertain significance (Jul 12, 2023)
3-52473778-G-A			Benign (Mar 29, 2018)
3-52476468-T-A		not specified	Uncertain significance (Mar 02, 2023)
3-52476505-T-C		not specified	Uncertain significance (Jun 11, 2021)
3-52476510-G-T		not specified	Uncertain significance (May 11, 2022)
3-52476525-G-A		not specified	Likely benign (Jun 27, 2022)
3-52476553-C-T		not specified	Uncertain significance (Jan 23, 2024)
3-52476576-G-G			Benign (Jun 16, 2018)
3-52478224-G-A		not specified	Uncertain significance (Aug 22, 2023)
3-52478251-A-G		not specified	Uncertain significance (Sep 27, 2021)
3-52478256-G-C		not specified	Uncertain significance (Oct 20, 2023)
3-52478461-C-T		not specified	Uncertain significance (Aug 11, 2021)
3-52478462-G-A		not specified	Uncertain significance (Apr 06, 2022)
3-52479825-A-G			Benign (May 30, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NISCH	protein_coding	protein_coding	ENST00000345716	21	37954

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00557	125723	0	24	125747	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.30	741	939	0.789	0.0000620	9769
Missense in Polyphen		182	299.18	0.60833		3126
Synonymous	-0.847	447	425	1.05	0.0000306	3116
Loss of Function	5.95	10	59.5	0.168	0.00000264	707

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000276
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures. {ECO:0000250, ECO:0000269|PubMed:10882231, ECO:0000269|PubMed:12868002, ECO:0000269|PubMed:15028619, ECO:0000269|PubMed:15028621, ECO:0000269|PubMed:15475348}.

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.554
• rvis_EVS: -2.31
• rvis_percentile_EVS: 1.2

Haploinsufficiency Scores

• pHI: 0.107
• hipred: Y
• hipred_score: 0.671
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.901

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nisch
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; skeleton 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); hearing/vestibular/ear phenotype; immune system phenotype

Gene ontology

• Biological process: glucose metabolic process;apoptotic process;regulation of blood pressure;Rac protein signal transduction;actin cytoskeleton organization;negative regulation of cell migration;regulation of synaptic transmission, GABAergic;norepinephrine secretion
• Cellular component: cytoplasm;early endosome;cytosol;plasma membrane;membrane;recycling endosome
• Molecular function: integrin binding;protein binding;protein kinase binding;phosphatidylinositol binding;identical protein binding