NCS1

neuronal calcium sensor 1, the group of EF-hand domain containing

Basic information

Region (hg38): 9:130172403-130237303

Previous symbols: [ "FREQ" ]

Links

ENSG00000107130 ∙ NCBI:23413 ∙ OMIM:603315 ∙ HGNC:3953 ∙ Uniprot:P62166 ∙ 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 NCS1 gene.

• not provided (3 variants)
• Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCS1 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			3			3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	3	1	1

Variants in NCS1

This is a list of pathogenic ClinVar variants found in the NCS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-130217928-C-A			Likely benign (Aug 21, 2018)
9-130219765-C-T		not specified	Uncertain significance (Sep 26, 2022)
9-130222698-A-G		not specified	Uncertain significance (Dec 13, 2021)
9-130222748-C-T			Benign (Feb 25, 2018)
9-130223091-G-A		not specified	Uncertain significance (Dec 28, 2023)
9-130223167-G-T			Benign (Jan 23, 2018)
9-130226473-G-C		not specified	Uncertain significance (Mar 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCS1	protein_coding	protein_coding	ENST00000372398	7	64727

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.664	0.335	125743	0	4	125747	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.22	43	108	0.399	0.00000679	1264
Missense in Polyphen		13	45.187	0.28769		512
Synonymous	0.972	40	48.6	0.823	0.00000368	343
Loss of Function	2.71	2	12.2	0.164	6.17e-7	141

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)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin (By similarity). Stimulates PI4KB kinase activity (By similarity). Involved in long-term synaptic plasticity through its interaction with PICK1 (By similarity). May also play a role in neuron differentiation through inhibition of the activity of N- type voltage-gated calcium channel (By similarity). {ECO:0000250}.
• Pathway: regulation of ck1/cdk5 by type 1 glutamate receptors (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.693
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ncs1
• 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); vision/eye phenotype

Gene ontology

• Biological process: regulation of neuron projection development;positive regulation of exocytosis;phosphatidylinositol-mediated signaling;calcium ion transmembrane transport;regulation of presynaptic cytosolic calcium ion concentration;regulation of synaptic vesicle exocytosis
• Cellular component: cytoplasm;Golgi apparatus;plasma membrane;postsynaptic density;cell junction;dendrite;dense core granule;intracellular membrane-bounded organelle;calyx of Held;postsynaptic membrane;perinuclear region of cytoplasm;glutamatergic synapse;presynaptic cytosol;postsynaptic cytosol
• Molecular function: magnesium ion binding;voltage-gated calcium channel activity;calcium ion binding;protein binding;protein kinase binding;voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels