SZT2

SZT2 subunit of KICSTOR complex, the group of MicroRNA protein coding host genes|KICSTOR complex

Basic information

Region (hg38): 1:43389882-43454247

Previous symbols: [ "C1orf84", "KIAA0467" ]

Links

ENSG00000198198 ∙ NCBI:23334 ∙ OMIM:615463 ∙ HGNC:29040 ∙ Uniprot:Q5T011 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 18 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 18 (Definitive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 18 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 18 (Strong), mode of inheritance: AR
• genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 18 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 18	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	21835308; 23932106
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SZT2 gene.

• not_provided (3175 variants)
• Inborn_genetic_diseases (734 variants)
• Developmental_and_epileptic_encephalopathy,_18 (624 variants)
• not_specified (112 variants)
• SZT2-related_disorder (77 variants)
• Self-limited_epilepsy_with_centrotemporal_spikes (11 variants)
• See_cases (3 variants)
• Encephalocele (2 variants)
• Severe_hydrocephalus (2 variants)
• Developmental_and_epileptic_encephalopathy (2 variants)
• Seizure (2 variants)
• Obesity (1 variants)
• Hereditary_spherocytosis_type_3 (1 variants)
• Global_developmental_delay (1 variants)
• Generalized_epilepsy (1 variants)
• Intellectual_disability (1 variants)
• Developmental_and_epileptic_encephalopathy,_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SZT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001365999.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			20	883	4	907
missense	7	7	1554	62	6	1636
nonsense	50	17	1			68
start loss						0
frameshift	62	12	3			77
splice donor/acceptor (+/-2bp)	3	34	13	1		51
Total	122	70	1591	946	10

Highest pathogenic variant AF is 0.000047088623

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SZT2	protein_coding	protein_coding	ENST00000562955	71	62769

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125598	0	150	125748	0.000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.60	1666	1.99e+3	0.836	0.000126	21596
Missense in Polyphen		719	957.36	0.75102		10436
Synonymous	0.228	768	776	0.990	0.0000437	7211
Loss of Function	8.52	61	187	0.327	0.0000117	1842

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000934	0.000909
Ashkenazi Jewish	0.000216	0.000198
East Asian	0.000880	0.000870
Finnish	0.000312	0.000231
European (Non-Finnish)	0.000686	0.000668
Middle Eastern	0.000880	0.000870
South Asian	0.00102	0.00101
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 (PubMed:28199306, PubMed:28199315). May play a role in the cellular response to oxidative stress (By similarity). {ECO:0000250|UniProtKB:A2A9C3, ECO:0000269|PubMed:28199306, ECO:0000269|PubMed:28199315}.

Recessive Scores

• pRec: 0.0920

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Gene ontology

• Biological process: central nervous system development;post-embryonic development;corpus callosum morphogenesis;cellular response to amino acid starvation;cellular response to glucose starvation;pigmentation;protein localization to lysosome;regulation of superoxide dismutase activity;negative regulation of TORC1 signaling
• Cellular component: lysosomal membrane;peroxisome;GATOR2 complex;KICSTOR complex;GATOR1 complex
• Molecular function: molecular_function;protein binding