KICS2

KICSTOR subunit 2, the group of KICSTOR complex

Basic information

Region (hg38): 12:64186316-64222296

Previous symbols: [ "C12orf66" ]

Links

ENSG00000174206 ∙ NCBI:144577 ∙ OMIM:617420 ∙ HGNC:26517 ∙ Uniprot:Q96MD2 ∙ 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 KICS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KICS2 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			1		2	3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	1	0	3

Variants in KICS2

This is a list of pathogenic ClinVar variants found in the KICS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-64193904-C-G			Benign (Dec 14, 2017)
12-64194115-G-A			Benign (Dec 14, 2017)
12-64215782-T-C			Benign (Dec 14, 2017)
12-64215847-C-T		not specified	Uncertain significance (Aug 02, 2021)
12-64222031-G-C		not specified	Conflicting classifications of pathogenicity (Mar 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KICS2	protein_coding	protein_coding	ENST00000398055	3	35981

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.442	0.557	124783	0	10	124793	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	180	247	0.729	0.0000125	2941
Missense in Polyphen		41	70.736	0.57962		974
Synonymous	1.34	85	102	0.832	0.00000545	867
Loss of Function	2.75	3	14.2	0.212	6.90e-7	177

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.000104	0.0000993
East Asian	0.00	0.00
Finnish	0.0000467	0.0000464
European (Non-Finnish)	0.00000888	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose. {ECO:0000269|PubMed:28199306}.

Intolerance Scores

• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.654
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: BC048403
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: cellular response to amino acid starvation;cellular response to glucose starvation;protein localization to lysosome;negative regulation of TORC1 signaling
• Cellular component: lysosomal membrane;KICSTOR complex