AKT1S1

AKT1 substrate 1, the group of MTOR complex 1

Basic information

Region (hg38): 19:49869033-49878459

Links

ENSG00000204673 ∙ NCBI:84335 ∙ OMIM:610221 ∙ HGNC:28426 ∙ Uniprot:Q96B36 ∙ 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 AKT1S1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKT1S1 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				2	2	4
missense			30	1		31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	30	3	2

Variants in AKT1S1

This is a list of pathogenic ClinVar variants found in the AKT1S1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-49869930-T-C		not specified	Uncertain significance (Sep 27, 2021)
19-49869933-A-T		not specified	Uncertain significance (Nov 20, 2023)
19-49869953-G-C		not specified	Uncertain significance (Jun 29, 2023)
19-49869964-G-A		not specified	Uncertain significance (Mar 20, 2024)
19-49869976-C-G		not specified	Uncertain significance (Oct 13, 2023)
19-49869986-C-A		not specified	Uncertain significance (May 09, 2023)
19-49871584-C-G		not specified	Uncertain significance (Sep 14, 2021)
19-49871665-G-T		not specified	Uncertain significance (Mar 29, 2023)
19-49871695-G-T		not specified	Uncertain significance (Sep 20, 2024)
19-49871844-G-C		not specified	Uncertain significance (Mar 18, 2024)
19-49871866-C-T		not specified	Likely benign (Dec 19, 2023)
19-49871884-A-T		not specified	Uncertain significance (Oct 18, 2021)
19-49872931-A-G		not specified	Uncertain significance (Mar 20, 2024)
19-49872948-G-A			Benign (Oct 10, 2018)
19-49872952-G-T		not specified	Uncertain significance (Mar 16, 2022)
19-49872955-T-C		not specified	Uncertain significance (Mar 25, 2024)
19-49872977-C-T		not specified	Uncertain significance (Dec 06, 2023)
19-49873060-G-A		not specified	Uncertain significance (Feb 17, 2024)
19-49873070-G-A		not specified	Uncertain significance (Dec 07, 2024)
19-49873070-G-C		not specified	Uncertain significance (Aug 27, 2024)
19-49873106-C-T		not specified	Uncertain significance (Dec 28, 2022)
19-49873118-G-A		not specified	Uncertain significance (Jun 26, 2024)
19-49873131-C-T			Benign (Jul 16, 2018)
19-49873132-G-A		not specified	Uncertain significance (Jun 21, 2023)
19-49873150-T-C		not specified	Uncertain significance (Aug 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKT1S1	protein_coding	protein_coding	ENST00000391835	5	9422

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.111	0.863	125736	0	6	125742	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.642	134	157	0.856	0.00000995	1686
Missense in Polyphen		47	70.453	0.66711		810
Synonymous	0.712	63	70.6	0.892	0.00000490	603
Loss of Function	1.91	3	9.29	0.323	4.60e-7	109

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000619	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000164	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunit of mTORC1, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection. {ECO:0000269|PubMed:16174443, ECO:0000269|PubMed:17277771, ECO:0000269|PubMed:17386266}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Target Of Rapamycin (TOR) Signaling;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Steatosis AOP;Pathways in clear cell renal cell carcinoma;Senescence and Autophagy in Cancer;Disease;Signal Transduction;HSF1-dependent transactivation;Cellular responses to stress;mTORC1-mediated signalling;mTOR signalling;insulin Mam;Cellular responses to external stimuli;PIP3 activates AKT signaling;Cellular response to heat stress;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;AKT phosphorylates targets in the cytosol;Intracellular signaling by second messengers;mTOR signaling pathway;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);LKB1 signaling events (Consensus)

Recessive Scores

• pRec: 0.214

Intolerance Scores

• loftool: 0.503
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.640
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Akt1s1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of protein kinase activity;negative regulation of TOR signaling;regulation of apoptotic process;regulation of neuron apoptotic process;negative regulation of cell size;neurotrophin TRK receptor signaling pathway;regulation of cellular response to heat
• Cellular component: nucleoplasm;cytoplasm;cytosol;TORC1 complex
• Molecular function: protein binding