AKT3
AKT serine/threonine kinase 3, the group of Pleckstrin homology domain containing|AKT kinases
Basic information
Region (hg38): 1:243488232-243851079
Links
Phenotypes
GenCC
Source:
- megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (Strong), mode of inheritance: AD
- megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (Strong), mode of inheritance: Somatic mosaicism
- megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (Strong), mode of inheritance: AD
- megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (Strong), mode of inheritance: AD
- megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (Supportive), mode of inheritance: AD
- megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (Strong), mode of inheritance: AD
- overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (Definitive), mode of inheritance: AD
- microcephaly (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 | AD | 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 | Dermatologic; Neurologic | 22729224; 22729223; 23745724 |
ClinVar
This is a list of variants' phenotypes submitted to
- Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (84 variants)
- not provided (74 variants)
- Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 (20 variants)
- not specified (16 variants)
- Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 (15 variants)
- Inborn genetic diseases (7 variants)
- Bardet-Biedl syndrome (4 variants)
- Renal dysplasia and retinal aplasia (4 variants)
- AKT3-related condition (3 variants)
- Bardet-Biedl syndrome 16 (3 variants)
- SDCCAG8-related condition (3 variants)
- Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (3 variants)
- Senior-Loken syndrome 7 (3 variants)
- AKT3-Related Disorder (1 variants)
- See cases (1 variants)
- Global developmental delay;Macrocephaly;Capillary hemangioma;Polymicrogyria (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKT3 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 | 25 | 30 | ||||
| missense | 26 | 38 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 2 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region ? | 2 | 5 | 7 | |||
| non coding ? | 22 | 67 | 21 | 110 | ||
| Total | 4 | 6 | 54 | 94 | 25 |
Variants in AKT3
This is a list of pathogenic ClinVar variants found in the AKT3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-243488997-G-C | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Likely benign (May 19, 2022) | ||
| 1-243489008-C-T | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (Feb 03, 2022) | ||
| 1-243489010-C-T | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Likely benign (Dec 13, 2023) | ||
| 1-243489011-C-T | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Uncertain significance (Jul 13, 2023) | ||
| 1-243489015-C-T | not specified • Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (Nov 02, 2023) | ||
| 1-243489017-A-AAGGCAGCTGGATAAGCAC | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Uncertain significance (Jun 05, 2021) | ||
| 1-243489032-G-A | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Likely benign (Mar 15, 2023) | ||
| 1-243489041-G-A | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (Mar 26, 2020) | ||
| 1-243489049-C-T | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Uncertain significance (Aug 01, 2022) | ||
| 1-243489054-C-G | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Uncertain significance (Apr 06, 2022) | ||
| 1-243489056-G-A | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (Jan 02, 2022) | ||
| 1-243489059-G-A | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (Oct 23, 2023) | ||
| 1-243489062-G-C | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 • SDCCAG8-related disorder | Likely benign (Oct 09, 2023) | ||
| 1-243489066-C-G | Inborn genetic diseases | Uncertain significance (Mar 20, 2023) | ||
| 1-243489068-C-T | Likely benign (Jun 27, 2018) | |||
| 1-243489081-A-T | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Uncertain significance (Aug 09, 2022) | ||
| 1-243489083-C-T | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Likely benign (Oct 09, 2022) | ||
| 1-243489086-G-A | not specified • Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (Jul 09, 2022) | ||
| 1-243489089-T-C | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 | Likely benign (Sep 12, 2022) | ||
| 1-243489095-G-A | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 • Bardet-Biedl syndrome 16 • Senior-Loken syndrome 7 | Conflicting classifications of pathogenicity (Dec 07, 2023) | ||
| 1-243489095-GGA-G | not specified | Uncertain significance (Oct 03, 2022) | ||
| 1-243489098-G-A | Bardet-Biedl syndrome 16;Senior-Loken syndrome 7 • SDCCAG8-related disorder | Likely benign (Dec 07, 2023) | ||
| 1-243489101-G-A | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (Dec 14, 2021) | ||
| 1-243489106-G-A | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Uncertain significance (Aug 17, 2023) | ||
| 1-243489113-G-A | Senior-Loken syndrome 7;Bardet-Biedl syndrome 16 | Likely benign (May 20, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| AKT3 | protein_coding | protein_coding | ENST00000366539 | 13 | 362847 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000424 | 124833 | 0 | 1 | 124834 | 0.00000401 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.95 | 76 | 252 | 0.301 | 0.0000127 | 3181 |
| Missense in Polyphen | 18 | 106.87 | 0.16843 | 1408 | ||
| Synonymous | 0.173 | 79 | 81.0 | 0.976 | 0.00000391 | 841 |
| Loss of Function | 4.61 | 1 | 26.7 | 0.0374 | 0.00000134 | 354 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000293 | 0.0000293 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: AKT3 is one of 3 closely related serine/threonine- protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase- dependent apoptosis. {ECO:0000269|PubMed:18524868, ECO:0000269|PubMed:21191416}.;
- Disease
- DISEASE: Note=AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.; DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (MPPH2) [MIM:615937]: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. {ECO:0000269|PubMed:22500628, ECO:0000269|PubMed:22729223, ECO:0000269|PubMed:22729224, ECO:0000269|PubMed:23745724}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Platelet activation - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Regulation of lipolysis in adipocytes - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Melanoma - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Influenza A - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Carbohydrate digestion and absorption - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Human papillomavirus infection - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;VEGF Signaling Pathway;IGF-Core;Regulation of toll-like receptor signaling pathway;Integrin-mediated Cell Adhesion;Signaling Pathways in Glioblastoma;Signal Transduction of S1P Receptor;Focal Adhesion;Overview of nanoparticle effects;MAPK Signaling Pathway;Chemokine signaling pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Lipid Metabolism Pathway;miRNA regulation of prostate cancer signaling pathways;Endometrial cancer;PI3K-Akt Signaling Pathway;MET in type 1 papillary renal cell carcinoma;Chromosomal and microsatellite instability in colorectal cancer;Ras Signaling;EMT transition in Colorectal Cancer;ErbB Signaling Pathway;DNA Damage Response (only ATM dependent);Toll-like Receptor Signaling Pathway;Developmental Biology;Signaling by GPCR;RUNX2 regulates genes involved in cell migration;Transcriptional regulation by RUNX2;Disease;Signal Transduction;Gene expression (Transcription);Vesicle-mediated transport;VEGFA-VEGFR2 Pathway;Membrane Trafficking;Generic Transcription Pathway;Regulation of PTEN stability and activity;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;CTLA4 inhibitory signaling;Costimulation by the CD28 family;RNA Polymerase II Transcription;Activation of BAD and translocation to mitochondria ;Activation of BH3-only proteins;Intrinsic Pathway for Apoptosis;IGF signaling;Immune System;Apoptosis;Programmed Cell Death;Adaptive Immune System;Cyclin E associated events during G1/S transition ;AKT phosphorylates targets in the nucleus;insulin Mam;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;TP53 Regulates Metabolic Genes;S Phase;Downregulation of ERBB2:ERBB3 signaling;Downregulation of ERBB2 signaling;IL-7 signaling;Rab regulation of trafficking;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;PTEN Regulation;PIP3 activates AKT signaling;JAK STAT pathway and regulation;PDGF;G1/S Transition;EPO signaling;Regulation of TP53 Activity through Association with Co-factors;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Negative regulation of the PI3K/AKT network;Signaling by VEGF;Signaling by ERBB2;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;RAB GEFs exchange GTP for GDP on RABs;Cell Cycle;Signaling by Receptor Tyrosine Kinases;AKT phosphorylates targets in the cytosol;VEGF;Cell Cycle, Mitotic;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;Intracellular signaling by second messengers;Diseases of signal transduction;Regulation of beta-cell development;S1P3 pathway;Class I PI3K signaling events mediated by Akt;CD4 T cell receptor signaling-NFkB cascade;VEGFR2 mediated vascular permeability;AKT-mediated inactivation of FOXO1A;Regulation of gene expression in beta cells;insulin;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.250
Intolerance Scores
- loftool
- 0.341
- rvis_EVS
- -0.25
- rvis_percentile_EVS
- 35.42
Haploinsufficiency Scores
- pHI
- 0.517
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.627
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Akt3
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; 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); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system 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);
Gene ontology
- Biological process
- mitochondrial genome maintenance;positive regulation of endothelial cell proliferation;protein phosphorylation;signal transduction;peptidyl-serine phosphorylation;positive regulation of TOR signaling;intracellular signal transduction;positive regulation of blood vessel endothelial cell migration;positive regulation of cell size;brain morphogenesis;homeostasis of number of cells within a tissue;positive regulation of cell migration involved in sprouting angiogenesis;positive regulation of vascular endothelial cell proliferation;positive regulation of artery morphogenesis;negative regulation of cellular senescence
- Cellular component
- nucleus;cytoplasm;membrane
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding