KICS2

protein-coding

KICSTOR subunit 2, the group of KICSTOR complex

Gene summary

Involved in several processes, including cellular response to amino acid starvation; cellular response to glucose starvation; and negative regulation of TORC1 signaling. Part of KICSTOR complex. Implicated in autosomal recessive intellectual developmental disorder 83. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C12orf66

MANE transcript

NM_152440.5

Inheritance

ClinVar variants

P:5U:3B:4

Top phenotype

Intellectual developmental disorder, autosomal recessive 83

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr12:64,186,316-64,222,296

External References & Databases

Ensembl (ENSG00000174206)

Transcript & Mutation Effects

hg38 • Region Span ~36.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KICS2 variants in ClinVar

3 Conditions Cataloged

Intellectual developmental disorder, autosomal recessive 83Total: 5

not providedTotal: 4

not specifiedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152440.5. 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	2 clinvar		3 clinvar	1 clinvar	2 clinvar	8
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	5	0	3	1	3	12

Highest pathogenic variant AF is 0.0000065715976

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152440.5	RefSeq	NP_689653.4	3	MANE Select
ENST00000398055.8	Ensembl	ENSP00000381132.4	3	MANE Select
NM_001300940.2	RefSeq	NP_001287869.2	4	Standard
NM_001300941.2	RefSeq	NP_001287870.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398055
Coding exons: 3
Length: 35981
Individuals with no LoFs: 124783
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 124793
p: 0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	180	247	0.729	0.0000125	2941
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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