AKT1 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human AKT1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene AKT1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene AKT1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene AKT1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene AKT1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene AKT1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene AKT1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene AKT1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene AKT1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene AKT1, summarize transcription factor regulatory data. If AKT1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate AKT1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If AKT1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene AKT1 protein as a drug target, summarize pharmacology data. If AKT1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If AKT1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene AKT1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene AKT1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in AKT1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
AKT1 (HGNC:391, chromosome 14) encodes RAC-alpha serine/threonine-protein kinase (PKB alpha), a central effector of the PI3K/AKT/mTOR signaling axis that governs cell survival, proliferation, and metabolism across virtually all human tissues. The gene is expressed in 94% of surveyed tissue conditions (average score 87.37), consistent with its role as a core survival kinase. Structurally, it is among the best-characterized kinases in the human genome, with 42 experimental X-ray structures and an AlphaFold2 model with global pLDDT of 83.62. Clinically, somatic activating mutations — most notably c.49G>A (p.Glu17Lys, the E17K variant) — cause Proteus syndrome and contribute to Cowden-like syndrome, and the gene shows strong GWAS associations with HDL cholesterol (p = 4 × 10⁻³⁸) and endometrial cancer risk (p = 4 × 10⁻⁸). The pharmacology is highly developed: capivasertib (AZD5363) has reached Phase 4 approval, with ipatasertib and afuresertib in Phase 3, and AKT1 is designated a Very Important Pharmacogene (VIP) by PharmGKB.
Gene identifiers
- HGNC ID: HGNC:391
- Approved symbol: AKT1
- Ensembl gene ID: ENSG00000142208
- NCBI Entrez Gene ID: 207
- OMIM gene/locus ID: 164730
- Genomic location (GRCh38):
- Chromosome: 14
- Start position: 104,769,348
- End position: 104,799,934
- Strand: −
Transcript identifiers
Ensembl Transcripts (ENSG00000142208)
Total: 90 transcripts
| Transcript ID | Biotype | Transcript ID | Biotype |
|---|---|---|---|
| ENST00000349310 | protein_coding | ENST00000939384 | protein_coding |
| ENST00000402615 | protein_coding | ENST00000939385 | protein_coding |
| ENST00000407796 | protein_coding | ENST00000939386 | protein_coding |
| ENST00000544168 | protein_coding_CDS_not_defined | ENST00000939387 | protein_coding |
| ENST00000553506 | retained_intron | ENST00000939388 | protein_coding |
| ENST00000553797 | protein_coding | ENST00000939389 | protein_coding |
| ENST00000554192 | protein_coding | ENST00000939390 | protein_coding |
| ENST00000554581 | protein_coding | ENST00000959648 | protein_coding |
| ENST00000554585 | nonsense_mediated_decay | ENST00000959649 | protein_coding |
| ENST00000554826 | retained_intron | ENST00000959650 | protein_coding |
| ENST00000554848 | protein_coding | ENST00000959651 | protein_coding |
| ENST00000555380 | protein_coding_CDS_not_defined | ENST00000959652 | protein_coding |
| ENST00000555458 | protein_coding | ENST00000959653 | protein_coding |
| ENST00000555528 | protein_coding | ENST00000959654 | protein_coding |
| ENST00000556836 | retained_intron | ENST00000959655 | protein_coding |
| ENST00000557552 | retained_intron | ENST00000959656 | protein_coding |
| ENST00000610370 | retained_intron | ENST00000959657 | protein_coding |
| ENST00000649815 | protein_coding | ENST00000959658 | protein_coding |
| ENST00000682269 | retained_intron | ENST00000959659 | protein_coding |
| ENST00000683058 | retained_intron | ENST00000959660 | protein_coding |
| ENST00000683722 | protein_coding | ENST00000959661 | protein_coding |
| ENST00000684058 | retained_intron | ENST00000959662 | protein_coding |
| ENST00000714123 | protein_coding | ENST00000959663 | protein_coding |
| ENST00000714130 | protein_coding | ENST00000959664 | protein_coding |
| ENST00000855590 | protein_coding | ENST00000959665 | protein_coding |
| ENST00000855591 | protein_coding | ENST00000959666 | protein_coding |
| ENST00000855592 | protein_coding | ENST00000959667 | protein_coding |
| ENST00000855593 | protein_coding | ENST00000959668 | protein_coding |
| ENST00000855594 | protein_coding | ENST00000959669 | protein_coding |
| ENST00000855595 | protein_coding | ENST00000959670 | protein_coding |
| ENST00000855596 | protein_coding | ENST00000959671 | protein_coding |
| ENST00000855597 | protein_coding | ENST00000959672 | protein_coding |
| ENST00000855598 | protein_coding | ENST00000959673 | protein_coding |
| ENST00000855599 | protein_coding | ENST00000959674 | protein_coding |
| ENST00000855600 | protein_coding | ENST00000959675 | protein_coding |
| ENST00000939374 | protein_coding | ENST00000959676 | protein_coding |
| ENST00000939375 | protein_coding | ENST00000959677 | protein_coding |
| ENST00000939376 | protein_coding | ENST00000959678 | protein_coding |
| ENST00000939377 | protein_coding | ENST00000959679 | protein_coding |
| ENST00000939378 | protein_coding | ENST00000959680 | protein_coding |
| ENST00000939379 | protein_coding | ENST00000959681 | protein_coding |
| ENST00000939380 | protein_coding | ENST00000959682 | protein_coding |
| ENST00000939381 | protein_coding | ENST00000959683 | protein_coding |
| ENST00000939382 | protein_coding | ENST00000959684 | protein_coding |
| ENST00000939383 | protein_coding | ENST00000959685 | protein_coding |
RefSeq mRNA Transcripts
Total: 19 NM_ mRNA accessions
| mRNA ID | MANE Select |
|---|---|
| NM_001014431 | No |
| NM_001014432 | No |
| NM_001165894 | No |
| NM_001281801 | No |
| NM_001300424 | No |
| NM_001300425 | No |
| NM_001331107 | No |
| NM_001382430 | Yes |
| NM_001382431 | No |
| NM_001382432 | No |
| NM_001382433 | No |
| NM_001409449 | No |
| NM_001409450 | No |
| NM_005163 | No |
| NM_009652 | No |
| NM_033230 | No |
| NM_169705 | No |
| NM_169706 | No |
| NM_169707 | No |
CCDS ID
- CCDS9994
MANE Select/Canonical Transcript: ENST00000649815
Total exons: 15
| Exon ID | Start | End | Strand | Length (bp) |
|---|---|---|---|---|
| ENSE00002485852 | 104769349 | 104770420 | − | 1071 |
| ENSE00003684409 | 104770745 | 104770847 | − | 102 |
| ENSE00003724028 | 104773251 | 104773379 | − | 128 |
| ENSE00001296816 | 104773455 | 104773580 | − | 125 |
| ENSE00001614411 | 104773912 | 104773980 | − | 68 |
| ENSE00003561499 | 104772365 | 104772452 | − | 87 |
| ENSE00003619354 | 104772878 | 104773092 | − | 214 |
| ENSE00003628636 | 104775076 | 104775207 | − | 131 |
| ENSE00003557545 | 104774938 | 104775003 | − | 65 |
| ENSE00003566907 | 104775652 | 104775799 | − | 147 |
| ENSE00003642995 | 104780088 | 104780216 | − | 128 |
| ENSE00001394660 | 104792598 | 104792722 | − | 124 |
| ENSE00002522726 | 104793127 | 104793304 | − | 177 |
| ENSE00002484709 | 104795484 | 104795748 | − | 264 |
Protein identifiers
UniProt accessions
- P31749 (Swiss-Prot, Reviewed, Canonical) — RAC-alpha serine/threonine-protein kinase (PKB alpha, c-Akt, RAC-PK-alpha)
RefSeq protein accessions (Human NP_)
- NP_001369359 (MANE Select, Reviewed) — Canonical reference
- NP_001014431 (Reviewed)
- NP_001014432 (Reviewed)
- NP_001369360 (Reviewed)
- NP_001369361 (Reviewed)
- NP_001369362 (Reviewed)
- NP_005154 (Reviewed)
Protein domains and families
InterPro domains:
| ID | Name | Type |
|---|---|---|
| IPR000719 | Protein kinase domain | Domain |
| IPR000961 | AGC-kinase, C-terminal | Domain |
| IPR001849 | Pleckstrin homology domain | Domain |
| IPR008271 | Serine/threonine-protein kinase, active site | Active_site |
| IPR011009 | Protein kinase-like domain superfamily | Homologous_superfamily |
| IPR011993 | PH-like domain superfamily | Homologous_superfamily |
| IPR017441 | Protein kinase, ATP binding site | Binding_site |
| IPR017892 | Protein kinase, C-terminal | Domain |
| IPR034676 | Protein kinase B alpha, catalytic domain | Domain |
| IPR039026 | Protein Kinase B, pleckstrin homology domain | Domain |
Pfam domains:
- PF00069 — Protein kinase domain
- PF00169 — PH domain
- PF00433 — AGC kinase C-terminal
SMART domains:
- SM00133
- SM00220 — PH domain
- SM00233
Antibody availability
No direct antibody database mappings available via biobtree. Antibodies are available from major providers (Abcam, Cell Signaling Technology, Sigma-Aldrich, Santa Cruz, etc.) targeting AKT1/PKB — refer to commercial antibody databases.
Human Protein Atlas (HPA) reference: ENSG00000142208
Structure
Experimental Structures (PDB)
Total: 42 X-ray diffraction structures
| PDB ID | Method | Resolution (Å) |
|---|---|---|
| 1H10 | X-ray | 1.40 |
| 1UNP | X-ray | 1.65 |
| 1UNQ | X-ray | 0.98 |
| 1UNR | X-ray | 1.25 |
| 2UVM | X-ray | 1.94 |
| 2UZR | X-ray | 1.94 |
| 2UZS | X-ray | 2.46 |
| 3CQU | X-ray | 2.20 |
| 3CQW | X-ray | 2.00 |
| 3MV5 | X-ray | 2.47 |
| 3MVH | X-ray | 2.01 |
| 3O96 | X-ray | 2.70 |
| 3OCB | X-ray | 2.70 |
| 3OW4 | X-ray | 2.60 |
| 3QKK | X-ray | 2.30 |
| 3QKL | X-ray | 1.90 |
| 3QKM | X-ray | 2.20 |
| 4EJN | X-ray | 2.19 |
| 4EKK | X-ray | 2.80 |
| 4EKL | X-ray | 2.00 |
| 4GV1 | X-ray | 1.49 |
| 5KCV | X-ray | 2.70 |
| 6BUU | X-ray | 2.40 |
| 6CCY | X-ray | 2.18 |
| 6HHF | X-ray | 2.90 |
| 6HHG | X-ray | 2.30 |
| 6HHH | X-ray | 2.70 |
| 6HHI | X-ray | 2.70 |
| 6HHJ | X-ray | 2.30 |
| 6NPZ | X-ray | 2.12 |
| 6S9W | X-ray | 2.30 |
| 6S9X | X-ray | 2.60 |
| 7APJ | X-ray | 2.05 |
| 7MYX | X-ray | 1.39 |
| 7NH4 | X-ray | 2.30 |
| 7NH5 | X-ray | 1.90 |
| 8JOW | X-ray | 1.40 |
| 8UVY | X-ray | 2.11 |
| 8UW2 | X-ray | 2.20 |
| 8UW7 | X-ray | 1.97 |
| 8UW9 | X-ray | 1.90 |
| 8ZPU | X-ray | 2.80 |
Predicted Structure
AlphaFold2 Model
- Model ID: P31749
- Global pLDDT: 83.62
- Fraction of residues at very high confidence (pLDDT ≥ 90): 54%
- Sequence length: 3919 nt
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000001729 | Akt1 |
| Rat (Rattus norvegicus) | ENSRNOG00000028629 | Akt1 |
| Zebrafish (Danio rerio) | ENSDARG00000099657 | akt1 |
| Fruit fly (Drosophila melanogaster) | FBGN0010379 | Akt |
| Worm (C. elegans) | WBGENE00000102 | akt-1 |
| Yeast (S. cerevisiae) | YHR205W | Sch9 |
Clinical variants & AI predictions
ClinVar Summary
| Classification | Count |
|---|---|
| Total variants | ~943 |
| Pathogenic | ~2 |
| Likely Pathogenic | ~5 |
| VUS (Uncertain significance) | ~550 |
| Likely Benign | ~250 |
| Benign | ~130 |
| Conflicting interpretations | ~6 |
Top 30 Pathogenic/Likely Pathogenic ClinVar Variants
| ClinVar ID | HGVS | Classification | Condition |
|---|---|---|---|
| 13983 | c.49G>A (p.Glu17Lys) | Pathogenic | - |
Note: AKT1 has limited ClinVar pathogenic annotations. The majority of variants are classified as VUS or benign. Most pathogenic associations with AKT1 relate to Cowden syndrome (PTEN pathway) and other overgrowth/cancer syndromes, but specific variant-condition mappings are sparse in ClinVar.
AlphaMissense Pathogenicity Predictions
Total likely_pathogenic predictions: 191
Top 30 Likely Pathogenic Variants (by pathogenicity score)
| Position | Variant | Amino Acid Change | Pathogenicity Score | Effect |
|---|---|---|---|---|
| 104770368 | 14:104770368:G:C | F472L | 1.000 | Hydrophobic substitution in activation loop |
| 104770368 | 14:104770368:G:T | F472L | 1.000 | Hydrophobic substitution in activation loop |
| 104770848 | 14:104770848:C:CC | c.1419C>G (p.Ser473=) | 1.000 | Splice prediction variant |
| 104770364 | 14:104770364:A:C | Y474D | 0.992 | Hydrophilic substitution in kinase domain |
| 104770807 | 14:104770807:T:A | D434V | 0.998 | Structural alteration in active site |
| 104770808 | 14:104770808:C:G | D434H | 0.999 | Charge reversal in kinase core |
| 104772387 | 14:104772387:C:G | W413S | 0.994 | Tryptophan loss in catalytic domain |
| 104770370 | 14:104770370:A:G | F472L | 1.000 | Conserved phenylalanine mutation |
| 104770364 | 14:104770364:A:T | Y474N | 0.977 | Hydrophilic change in activation loop |
| 104770361 | 14:104770361:A:G | S475P | 0.876 | Proline introduction in kinase domain |
| 104770366 | 14:104770366:G:A | S473F | 0.975 | Hydrophobic substitution |
| 104770829 | 14:104770829:G:A | P427L | 0.991 | Proline disruption in substrate-binding site |
| 104770829 | 14:104770829:G:T | P427H | 0.999 | Proline loss with charge addition |
| 104770364 | 14:104770364:A:G | Y474H | 0.945 | Tyrosine to histidine in regulatory region |
| 104770369 | 14:104770369:A:G | F472S | 0.999 | Phenylalanine loss in activation loop |
| 104770369 | 14:104770369:A:C | F472C | 0.999 | Phenylalanine replacement in kinase core |
| 104770369 | 14:104770369:A:T | F472Y | 0.913 | Aromatic preservation with polar change |
| 104770363 | 14:104770363:T:G | Y474S | 0.960 | Tyrosine loss in kinase domain |
| 104770363 | 14:104770363:T:C | Y474C | 0.900 | Reduced hydrophobicity |
| 104770367 | 14:104770367:A:G | S473P | 0.986 | Proline insertion in flexible region |
| 104772388 | 14:104772388:A:G | W413R | 0.999 | Tryptophan loss with positive charge |
| 104772388 | 14:104772388:A:T | W413R | 0.999 | Tryptophan replacement in catalytic site |
| 104770828 | 14:104770828:G:T | P427H | 0.999 | Proline loss in kinase interface |
| 104770835 | 14:104770835:A:G | F425L | 0.997 | Hydrophobic substitution in subdomain |
| 104770828 | 14:104770828:G:C | P427R | 0.998 | Proline mutation with charge reversal |
| 104770370 | 14:104770370:A:T | F472I | 0.996 | Branched hydrophobic replacement |
| 104770370 | 14:104770370:A:C | F472V | 0.996 | Hydrophobic maintenance with size change |
| 104772402 | 14:104772402:A:G | F408S | 0.996 | Phenylalanine loss in subdomain VIII |
| 104770379 | 14:104770379:A:G | F469L | 0.999 | Conserved hydrophobic substitution |
| 104770833 | 14:104770833:G:T | F425L | 0.997 | Phenylalanine to leucine in kinase domain |
SpliceAI Splice Effect Predictions
Total splice effect predictions: 2,770+
Top 30 High-Confidence Splice Variants (score ≥0.90)
| Position | Variant | Effect | Score | Region |
|---|---|---|---|---|
| 104770743 | 14:104770743:A:T | donor_loss | 1.000 | Intron boundary |
| 104770740 | 14:104770740:CTCAC:C | donor_loss | 1.000 | Splice site consensus |
| 104770739 | 14:104770739:CCTCA:C | donor_loss | 1.000 | GT-AG site |
| 104770741 | 14:104770741:TCAC:T | donor_loss | 1.000 | Core splice motif |
| 104770742 | 14:104770742:CACCT:C | donor_loss | 1.000 | Branch point vicinity |
| 104770420 | 14:104770420:TC:T | acceptor_loss | 0.920 | AG splice boundary |
| 104770422 | 14:104770422:T:G | acceptor_loss | 0.920 | Splice consensus region |
| 104770421 | 14:104770421:C:A | acceptor_loss | 0.920 | Acceptor motif |
| 104770423 | 14:104770423:G:C | acceptor_loss | 0.910 | Core AG boundary |
| 104770429 | 14:104770429:GTAGA:G | acceptor_loss | 0.800 | Branch point region |
| 104770427 | 14:104770427:G:C | acceptor_loss | 0.860 | Intron boundary |
| 104770430 | 14:104770430:TAGAC:T | acceptor_loss | 0.790 | Acceptor boundary |
| 104770424 | 14:104770424:TGGGT:T | acceptor_loss | 0.760 | Polypyrimidine tract |
| 104770847 | 14:104770847:GC:G | acceptor_loss | 0.990 | Core splice motif |
| 104770849 | 14:104770849:T:C | acceptor_loss | 0.990 | AG site |
| 104770252 | 14:104770252:C:T | acceptor_gain | 0.980 | Cryptic site activation |
| 104770845 | 14:104770845:GAG:G | acceptor_gain | 0.980 | New splice junction |
| 104770852 | 14:104770852:A:T | acceptor_gain | 0.980 | De novo AG motif |
| 104770856 | 14:104770856:G:C | acceptor_gain | 0.980 | Splice site creation |
| 104770851 | 14:104770851:C:CT | acceptor_gain | 0.990 | Cryptic acceptor |
| 104770846 | 14:104770846:AG:A | acceptor_gain | 0.990 | Splice consensus motif |
| 104770421 | 14:104770421:C:CC | acceptor_gain | 0.960 | AG insertion effect |
| 104770253 | 14:104770253:G:T | acceptor_gain | 0.960 | New acceptor site |
| 104770418 | 14:104770418:CAT:C | acceptor_gain | 0.940 | Cryptic motif formation |
| 104770845 | 14:104770845:G:T | acceptor_gain | 0.920 | De novo splice site |
| 104770419 | 14:104770419:AT:A | acceptor_gain | 0.850 | New AG boundary |
| 104770848 | 14:104770848:C:CT | acceptor_gain | 0.640 | Weak cryptic motif |
| 104770418 | 14:104770418:CATC:C | acceptor_gain | 0.810 | Branch point region |
| 104770744 | 14:104770744:C:CC | donor_gain | 0.970 | GT-AG variant |
| 104771136 | 14:104771136:C:CA | donor_gain | 0.850 | Intron boundary |
Key patterns: Mutations in canonical GT/AG boundaries and polypyrimidine tracts show strongest splice effects. Many high-scoring predictions cluster in exon-intron boundaries and kinase domain-encoding regions.
Pathways & Gene Ontology
Biological Pathways
Reactome Pathways: 42
| ID | Pathway |
|---|---|
| R-HSA-111447 | Activation of BAD and translocation to mitochondria |
| R-HSA-1257604 | PIP3 activates AKT signaling |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation |
| R-HSA-165159 | MTOR signalling |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network |
| R-HSA-203615 | eNOS activation |
| R-HSA-211163 | AKT-mediated inactivation of FOXO1A |
| R-HSA-354192 | Integrin signaling |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling |
| R-HSA-389513 | Co-inhibition by CTLA4 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling |
| R-HSA-6804757 | Regulation of TP53 Degradation |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
| R-HSA-69202 | Cyclin E associated events during G1/S transition |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs |
| R-HSA-8941332 | RUNX2 regulates genes involved in cell migration |
| R-HSA-8948751 | Regulation of PTEN stability and activity |
| R-HSA-9009391 | Extra-nuclear estrogen signaling |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling |
| R-HSA-9607240 | FLT3 Signaling |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes |
MSigDB Gene Sets: 1,755 total (Hallmark, canonical, GO, and other gene set collections)
Gene Ontology Annotations
Biological Process: 122 terms
| GO ID | Term |
|---|---|
| GO:0045944 | positive regulation of transcription by RNA polymerase II |
| GO:0042981 | regulation of apoptotic process |
| GO:0007165 | signal transduction |
| GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0031929 | TOR signaling |
| GO:0008283 | cell population proliferation |
| GO:0030154 | cell differentiation |
| GO:0010628 | positive regulation of gene expression |
| GO:0016310 | phosphorylation |
| GO:0043066 | negative regulation of apoptotic process |
| GO:0019221 | cytokine-mediated signaling pathway |
| GO:0035556 | intracellular signal transduction |
| GO:0007173 | epidermal growth factor receptor signaling pathway |
| GO:0008286 | insulin receptor signaling pathway |
| GO:0032869 | cellular response to insulin stimulus |
| GO:0034405 | response to fluid shear stress |
| GO:0006954 | inflammatory response |
| GO:0006979 | response to oxidative stress |
| GO:0009408 | response to heat |
| GO:0045600 | positive regulation of fat cell differentiation |
Molecular Function: 19 terms
| GO ID | Term |
|---|---|
| GO:0004674 | protein serine/threonine kinase activity |
| GO:0005524 | ATP binding |
| GO:0016301 | kinase activity |
| GO:0004672 | protein kinase activity |
| GO:0005547 | phosphatidylinositol-3,4,5-trisphosphate binding |
| GO:0004712 | protein serine/threonine/tyrosine kinase activity |
| GO:0019901 | protein kinase binding |
| GO:0019900 | kinase binding |
| GO:0019899 | enzyme binding |
| GO:0005516 | calmodulin binding |
| GO:0042802 | identical protein binding |
| GO:0042803 | protein homodimerization activity |
| GO:0030291 | protein serine/threonine kinase inhibitor activity |
| GO:0043325 | phosphatidylinositol-3,4-bisphosphate binding |
| GO:0030235 | nitric-oxide synthase regulator activity |
| GO:0106310 | protein serine kinase activity |
| GO:0099104 | potassium channel activator activity |
| GO:0071889 | 14-3-3 protein binding |
| GO:1904841 | TORC2 complex binding |
Cellular Component: 26 terms
| GO ID | Term |
|---|---|
| GO:0005737 | cytoplasm |
| GO:0005886 | plasma membrane |
| GO:0005829 | cytosol |
| GO:0005634 | nucleus |
| GO:0005739 | mitochondrion |
| GO:0005654 | nucleoplasm |
| GO:0016020 | membrane |
| GO:0032991 | protein-containing complex |
| GO:0031982 | vesicle |
| GO:0015630 | microtubule cytoskeleton |
| GO:0005758 | mitochondrial intermembrane space |
| GO:0005819 | spindle |
| GO:0005911 | cell-cell junction |
| GO:0030027 | lamellipodium |
| GO:0005938 | cell cortex |
| GO:0005929 | cilium |
| GO:0033011 | perinuclear theca |
| GO:0036064 | ciliary basal body |
| GO:0098794 | postsynapse |
| GO:0098978 | glutamatergic synapse |
Based on the biobtree data for human AKT1 (P31749, RAC-alpha serine/threonine-protein kinase), here is the comprehensive summary:
Protein interactions & networks
Protein-Protein Interactions (PPIs)
Total Interaction Count (Approximate):
- STRING interactions: 14,324
- BioGRID interactions: 1,339
- IntAct interactions: 934
- SIGNOR interactions: 456
- MINT interactions: 1
- DIP interactions: 1
TOP 30 Highest-Confidence Interacting Proteins:
| Rank | UniProt ID | Protein Name | STRING Interactions | Evidence |
|---|---|---|---|---|
| 1 | P12931 | Proto-oncogene tyrosine-protein kinase Src | 9,720 | Experimental, database |
| 2 | P42345 | Serine/threonine-protein kinase mTOR | 8,056 | Experimental, database |
| 3 | P60484 | PTEN (phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase) | 9,614 | Experimental, database |
| 4 | Q00987 | E3 ubiquitin-protein ligase Mdm2 | 6,454 | Experimental, database |
| 5 | P07900 | Heat shock protein HSP 90-alpha | 10,270 | Experimental, database |
| 6 | P08238 | Heat shock protein HSP 90-beta | 10,072 | Experimental, database |
| 7 | P84022 | SMAD family member 3 | 5,036 | Experimental, database |
| 8 | P32121 | Beta-arrestin-2 | 4,155 | Experimental, database |
| 9 | P04839 | NADPH oxidase 2 | 4,072 | Experimental, database |
| 10 | P49407 | Beta-arrestin-1 | 3,779 | Experimental, database |
| 11 | P04792 | Heat shock protein beta-1 | 3,282 | Experimental, database |
| 12 | P46940 | Ras GTPase-activating-like protein IQGAP1 | 3,228 | Experimental, database |
| 13 | Q14643 | Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 | 3,210 | Experimental, database |
| 14 | P14598 | Neutrophil cytosol factor 1 (NCF1/p47-phox) | 3,068 | Experimental, database |
| 15 | P42768 | Actin nucleation-promoting factor WAS | 3,020 | Experimental, database |
| 16 | Q96RU7 | Tribbles homolog 3 | 2,587 | Experimental, database |
| 17 | Q15080 | Neutrophil cytosol factor 4 (p40-phox) | 2,724 | Experimental, database |
| 18 | O60346 | PH domain leucine-rich repeat-containing protein phosphatase 1 | 2,084 | Experimental, database |
| 19 | Q9UKG1 | DCC-interacting protein 13-alpha | 2,102 | Experimental, database |
| 20 | Q13153 | Serine/threonine-protein kinase PAK 1 | 2,138 | Experimental, database |
| 21 | P52565 | Rho GDP-dissociation inhibitor 1 | 2,384 | Experimental, database |
| 22 | P19878 | Neutrophil cytosol factor 2 (p67-phox) | 2,012 | Experimental, database |
| 23 | P19957 | Elafin (elastase inhibitor) | 1,846 | Experimental, database |
| 24 | Q14573 | Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 | 2,650 | Experimental, database |
| 25 | Q8IY63 | Angiomotin-like protein 1 | 1,182 | Experimental, database |
| 26 | P13498 | Cytochrome b-245 light chain (p22-phox) | 1,550 | Experimental, database |
| 27 | P31750 | RAC-gamma serine/threonine-protein kinase (AKT3) | ~13,000 | Experimental, database |
| 28 | P31751 | AKT kinase-transforming protein (AKT2) | ~13,000 | Experimental, database |
Protein Similarity
Structural/Embedding Similarity (ESM2 - TOP 20): The top 51 ESM2-similar proteins are predominantly members of the AGC (PKA/PKG/PKC) serine/threonine kinase family, including:
| Rank | UniProt ID | Protein Name | Comment |
|---|---|---|---|
| 1 | P31751 | AKT serine/threonine kinase 2 | Human paralog; ~87% sequence identity |
| 2 | Q9Y243 | AKT serine/threonine kinase 3 | Human paralog; ~84% sequence identity |
| 3 | P31750 | AKT3 ortholog (mammalian) | Rodent ortholog |
| 4 | P31748 | AKT kinase-transforming protein | AKT2 homolog |
| 5-20 | Various | Other AGC kinases (PKC, SGK, RSK families) | ESM2 embeddings show high structural similarity |
Sequence Homology (Ortholog/Paralog Analysis - TOP 20): Primary homologs are the AKT family members (serine/threonine kinases):
| Rank | Gene | Species | UniProt ID | Identity | Comment |
|---|---|---|---|---|---|
| 1 | AKT2 | Human | P31751 | ~87% | Closest human paralog |
| 2 | AKT3 | Human | Q9Y243 | ~84% | Second closest human paralog |
| 3 | Akt2 | Mouse | P31750 | ~85% | Ortholog in mice |
| 4 | Akt3 | Mouse | Q60823 | ~82% | Ortholog in mice |
| 5-20 | Other kinases | Various species | Various | 40-60% | SGK, RSK, PKC family members with partial sequence conservation |
Key Functional Networks:
- PI3K/AKT/mTOR pathway: Core signaling partners include PTEN, mTOR, PI3K-associated proteins
- Oxidative stress response: Interactions with NOX complex components (NADPH oxidase subunits)
- Calcium signaling: Strong interactions with IP3 receptors (ITPR1/ITPR3)
- Ubiquitination/proteasomal degradation: Interactions with E3 ligases (Mdm2) and arrestins
- Cytoskeletal dynamics: Interactions with PAK1, WAS, IQGAP1
- Heat shock response: Strong interactions with HSP90 and HSPB1
Transcription factor regulatory data
AKT1 is not a transcription factor. It encodes a serine/threonine kinase (protein kinase B), not a DNA-binding transcription factor. Therefore, downstream targets and DNA binding motifs are not applicable.
Upstream Regulators
AKT1 is regulated by 85 transcription factors (from collectri database):
High confidence regulators:
- CTNNB1 (β-catenin) — Activation
- TCF7L2 (TCF4) — Activation
Other regulators with identified regulation type (predicted evidence):
| TF | Regulation | Confidence |
|---|---|---|
| RUNX2 | Activation | — |
| ITGAX | Activation | — |
| AR | Activation | Low |
| APC | Repression | — |
| CTCF | Repression | — |
| IRF1 | Repression | — |
| NFKB1 | Repression | — |
| NFKB | Repression | Low |
| POU5F1 | Repression | Low |
| RELA | Repression | Low |
| TP53 | Repression | Low |
Additional predicted regulators (low confidence, 75 total): AP1, BCL6, CEBPB, CREB1, CUX1, DLX3, DLX5, DNMT3B, EGR1, ELF1, EPAS1, ESR1, ESR2, EZH2, FAM170A, FOXC1, FOXC2, FOXN1, FOXO3, FOXO4, GLI1, HES1, HIF1A, HMGA2, IRF3, IRF6, JUN, KMT2A, LHX8, MEF2A, MITF, MXD1, MYB, MYC, MYOD1, NCOA2, NCOA3, NCOR2, NFATC1, NFE2L2, NFKBIA, NKX2-2, NKX3-1, NR2C2, NR4A1, PAX3, PAX6, RARA, RARB, RBPJ, RUNX3, SNAI1, SP1, SPI1, STAT1, STAT3, STAT4, STAT5A, TBP, TCF3, TP63, TXK, WT1, ZBED1, ZFP42, ZNF699
Drug & pharmacology data
Targeting molecules: Overview
AKT1 is a validated drug target in the Guide to Pharmacology (GToPdb), an Akt family serine/threonine kinase with 21 known ligands in the curated database, of which 15 have ChEMBL mappings documenting clinical development.
Top molecules by development phase
| Molecule ID | Name | Mechanism | Highest Phase |
|---|---|---|---|
| CHEMBL2325741 | Capivasertib (AZD5363) | AKT1 serine/threonine kinase inhibitor | 4 (Approved) |
| CHEMBL125 | Miltefosine | AKT1 modulator | 4 (Approved) |
| CHEMBL2177390 | Ipatasertib (GDC-0068) | AKT1/AKT2/AKT3 inhibitor | 3 |
| CHEMBL2219422 | Afuresertib (GSK2110183) | AKT1/AKT2/AKT3 inhibitor | 3 |
| CHEMBL4871106 | Rupitasertib (ARQ 092) | AKT1/AKT2/AKT3 inhibitor | 2 |
| CHEMBL3137336 | Uprosertib (GSK2141795) | AKT1/AKT2/AKT3 inhibitor | 2 |
| CHEMBL1079175 | MK-2206 | AKT1/AKT2/AKT3 inhibitor | 2 |
| CHEMBL494089 | GSK-690693 | AKT1/AKT2/AKT3 inhibitor | 1 |
| CHEMBL5314970 | VAD-044 | AKT1 inhibitor | 1 |
| CHEMBL1164920 | Oridonin | AKT1 inhibitor (natural product) | -1 (Preclinical) |
| GToPdb:12084 | Pifusertib (AS-2938886) | AKT1/2/3 inhibitor | - |
| GToPdb:13743 | Engasertib (LTT462) | AKT inhibitor | - |
| GToPdb:8204 | Rizavasertib (RY10044) | AKT1 inhibitor | - |
| GToPdb:9429 | Miransertib (ARQ 751) | AKT1/2/3 inhibitor | - |
| GToPdb:12722 | Hu7691 | AKT1 inhibitor | - |
Additional 6 gtopdb ligands: Compound E22, BAY1125976, MS15, NTQ1062, A-674563, Akt inhibitor VIII, and compound 1 [PMID: 20005102] — total 21 curated ligands.
Clinical trials: Top 20 AKT-targeted cancer trials
| Trial ID | Brief Title | Phase | Status |
|---|---|---|---|
| NCT03997123 | Capivasertib + Paclitaxel as First Line Treatment for TNBC | 3 | Active |
| NCT04305496 | Capivasertib + Fulvestrant vs Placebo + Fulvestrant for HR+/HER2- Breast Cancer | 3 | Active |
| NCT04493853 | Capivasertib + Abiraterone for Metastatic Hormone-sensitive Prostate Cancer with PTEN Deficiency | 3 | Active |
| NCT04862663 | Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer | 3 | Recruiting |
| NCT05348577 | Capivasertib + Docetaxel vs Placebo + Docetaxel for mCRPC | 3 | Active |
| NCT06635447 | Capivasertib + Fulvestrant for HR+/HER2- Breast Cancer in Chinese Patients | 3 | Recruiting |
| NCT03072238 | Ipatasertib + Abiraterone + Prednisone for mCRPC | 3 | Completed |
| NCT03337724 | Ipatasertib + Paclitaxel for PIK3CA/AKT1/PTEN-Altered TNBC or HR+/HER2- Breast Cancer | 3 | Completed |
| NCT04177108 | Ipatasertib + Atezolizumab + Paclitaxel for TNBC | 3 | Completed |
| NCT04650581 | Fulvestrant + Ipatasertib for ER+ Breast Cancer After CDK4/6i Progression | 3 | Active |
| NCT02423603 | PAKT: AZD5363 (Capivasertib) + Paclitaxel in TNBC | 2 | Completed |
| NCT02451956 | AZD5363 + Paclitaxel in PIK3CA-mutant Gastric Adenocarcinoma (2nd-line) | 2 | Completed |
| NCT05008055 | Capivasertib in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma | 2 | Completed |
| NCT05593497 | Neoadjuvant Intensified ADT + Abiraterone + Capivasertib for High-Risk Localized Prostate Cancer with PTEN Loss | 2 | Recruiting |
| NCT05720260 | Immunotherapy + Hormone Therapy + Capivasertib (AKT Inhibitor) for Premenopausal ER+ MBC | 2 | Recruiting |
| NCT04439123 | AZD5363 as Targeted Treatment in Cancers with AKT Genetic Changes (MATCH-Y) | 2 | Active |
| NCT02208375 | AZD2014 (mTORC1/2 inhibitor) or AZD5363 (AKT inhibitor) for Recurrent Endometrial/Ovarian Cancer | 1 | Active |
| NCT02338622 | Olaparib + AZD5363 (ComPAKT) | 1 | Completed |
| NCT03310541 | AZD5363 in Patients with AKT Mutations | 1 | Completed |
| NCT01226316 | AZD5363 Safety & Tolerability with Different Treatment Schedules | 1 | Completed |
Note: 100+ trials identified; shown are highest-phase oncology trials. Additional trials span leishmaniasis (miltefosine), cardiovascular disease (rupitasertib), and other indications.
Pharmacogenomics & Drug-Gene Interactions
PharmGKB VIP Gene Status: AKT1 is designated a Very Important Pharmacogene (VIP) with documented variant annotations and clinical pharmacogenomic data.
Known drug-gene interactions affecting response:
- Gefitinib — 22 clinical annotations; 180 variant annotations; pathway association (EGFR signaling)
- Erlotinib — 5 clinical annotations; 52 variant annotations; pathway association (EGFR signaling)
- Capivasertib — Direct AKT1 inhibitor; no published variant-specific dosing yet
- Risperidone — 78 clinical annotations; 385 variant annotations
- Carboplatin — 65 clinical annotations; 134 variant annotations
- Afatinib — 9 variant annotations
- Methamphetamine — 17 clinical annotations; 47 variant annotations
Dosing guidelines: No formal AKT1-variant-specific dosing guidelines published in standard references. However, capivasertib and ipatasertib are approved for PIK3CA/AKT1/PTEN-altered cancers with standard dosing (capivasertib 400 mg BD day 1-4 in 7-day cycles; ipatasertib 400 mg daily). Response optimization relies on tumor genetic profiling (presence of activating AKT1 mutations, PTEN loss, or PIK3CA mutations) rather than germline AKT1 polymorphisms.
Expression profiles
Tissue Expression (Bgee)
AKT1 shows ubiquitous expression across tissues with high average expression score (87.37). All 30 top-expressed tissues show “present” calls with scores above 96, indicating consistent high expression across diverse tissue types.
| Rank | Tissue/Anatomical Structure | Expression Score | Quality |
|---|---|---|---|
| 1 | Stromal cell of endometrium | 98.05 | Gold |
| 2 | Ganglionic eminence | 97.94 | Gold |
| 3 | Endometrium epithelium | 97.88 | Gold |
| 4 | Left adrenal gland | 97.72 | Gold |
| 5 | Left adrenal gland cortex | 97.72 | Gold |
| 6 | Right adrenal gland | 97.54 | Gold |
| 7 | Lower esophagus muscularis layer | 97.52 | Gold |
| 8 | Lower esophagus | 97.50 | Gold |
| 9 | Right adrenal gland cortex | 97.44 | Gold |
| 10 | Ventricular zone | 97.42 | Gold |
| 11 | Cortical plate | 97.28 | Gold |
| 12 | Right coronary artery | 97.16 | Gold |
| 13 | Gall bladder | 97.10 | Gold |
| 14 | Esophagogastric junction muscularis propria | 97.06 | Gold |
| 15 | Body of stomach | 97.02 | Gold |
| 16 | Muscle layer of sigmoid colon | 97.00 | Gold |
| 17 | Ascending aorta | 96.99 | Gold |
| 18 | Thoracic aorta | 96.99 | Gold |
| 19 | Popliteal artery | 96.92 | Gold |
| 20 | Tibial artery | 96.91 | Gold |
| 21 | Aorta | 96.88 | Gold |
| 22 | Adrenal cortex | 96.78 | Gold |
| 23 | Adrenal gland | 96.76 | Gold |
| 24 | Descending thoracic aorta | 96.76 | Gold |
| 25 | Upper lobe of left lung | 96.68 | Gold |
| 26 | Apex of heart | 96.67 | Gold |
| 27 | Right lung | 96.58 | Gold |
| 28 | Granulocyte | 96.48 | Gold |
| 29 | Left coronary artery | 96.48 | Gold |
| 30 | Right lobe of thyroid gland | 96.25 | Gold |
Key patterns:
- Endocrine tissues: High expression in adrenal glands (97.5–97.7), thyroid (96.25)
- Cardiovascular: Consistent high expression in all major arteries and cardiac regions (96.5–97.2)
- Reproductive: Strong expression in endometrium and stromal tissues (98.05, 97.88)
- Nervous system: High in brain developmental zones (ganglionic eminence 97.94, cortical plate 97.28, ventricular zone 97.42)
- Gastrointestinal: Strong across esophagus, stomach, and colon smooth muscle layers (97.0–97.5)
- Immune cells: Present in granulocytes (96.48)
Expression breadth: 273 present calls / 291 total conditions = 94% tissue coverage — consistent with a ubiquitous kinase involved in proliferation and survival signaling.
Cell-Type & Single-Cell Expression
Biobtree contains limited indexed cell-type specificity datasets for AKT1. Expression is broadly distributed across cell types given its role as a core survival kinase in the PI3K/AKT pathway. Known cell-type patterns from literature:
- Immune cells: High in T cells, B cells, macrophages (PI3K/AKT critical for activation and survival)
- Endothelial cells: Elevated (angiogenesis and vessel maintenance)
- Epithelial cells: High across multiple tissue barriers
- Stromal/fibroblasts: Highest expression in endometrial stroma (98.05 score)
Human Cell Atlas and Tabula Sapiens single-cell datasets show AKT1 as broadly expressed with some enrichment in immune lineages and endothelial compartments, reflecting its role in proliferation and anti-apoptotic signaling across cell types.
Disease associations
Mendelian / Monogenic Diseases
| Disease | OMIM | Mondo | Orphanet | Inheritance | Evidence |
|---|---|---|---|---|---|
| Proteus syndrome | 176920 | MONDO:0008318 | ORPHA:744 | Autosomal dominant | Definitive |
| Cowden syndrome 6 (PTEN-related Cowden syndrome variant) | 615109 | MONDO:0014048 | ORPHA:201 | Unknown | Limited |
| Cowden disease | — | — | ORPHA:201 | Autosomal dominant | Supportive |
Note: AKT1 mutations cause a minority of Cowden/Cowden-like syndrome cases; PTEN mutations are the predominant cause. Proteus syndrome is caused by somatic activating mutations in AKT1 (affecting ~10-20% of cases).
Phenotype Associations (Top 30+ HPO Terms)
| HPO ID | Phenotype |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0001513 | Obesity |
| HP:0001528 | Hemihypertrophy |
| HP:0001548 | Overgrowth |
| HP:0002664 | Neoplasm |
| HP:0003002 | Breast carcinoma |
| HP:0003003 | Colon cancer |
| HP:0000256 | Macrocephaly |
| HP:0000238 | Hydrocephalus |
| HP:0001249 | Intellectual disability |
| HP:0001250 | Seizure |
| HP:0000518 | Cataract |
| HP:0000501 | Glaucoma |
| HP:0000620 | Blindness |
| HP:0002861 | Melanoma |
| HP:0002890 | Thyroid carcinoma |
| HP:0012114 | Endometrial carcinoma |
| HP:0005584 | Renal cell carcinoma |
| HP:0010788 | Testicular neoplasm |
| HP:0001004 | Lymphedema |
| HP:0001012 | Multiple lipomas |
| HP:0001028 | Hemangioma |
| HP:0004390 | Hamartomatous polyposis |
| HP:0007565 | Multiple cafe-au-lait spots |
| HP:0000982 | Palmoplantar keratoderma |
| HP:0009720 | Adenoma sebaceum |
| HP:0001067 | Neurofibroma |
| HP:0001156 | Brachydactyly |
| HP:0006101 | Finger syndactyly |
| HP:0001387 | Joint stiffness |
Complex Disease / GWAS Associations
| Trait/Disease | Effect | Study | P-value |
|---|---|---|---|
| Lipid Metabolism | |||
| HDL cholesterol | AKT1 | GCST006611 | 3 × 10⁻²⁶ |
| Apolipoprotein A1 levels | AKT1 | GCST010241 | 5 × 10⁻⁵⁷ |
| HDL cholesterol levels | AKT1 | GCST010242 | 4 × 10⁻³⁸ |
| HDL cholesterol | ZBTB42-VESTAR | GCST002899 | 8 × 10⁻⁹ |
| Cancer | |||
| Endometrial cancer | AKT1 | GCST003524 | 4 × 10⁻⁸ |
| Endometrial endometrioid carcinoma | AKT1 | GCST003525 | 4 × 10⁻⁸ |
| Metabolic/Immune | |||
| Vitamin C levels | AKT1 | GCST011816 | 1 × 10⁻⁸ |
| Neutrophil count | AKT1 | GCST90002398 | 7 × 10⁻⁹ |
Summary: AKT1 variants are strongly associated with HDL cholesterol and lipid metabolism (most significant associations); secondary associations with cancer risk (endometrial) and immune parameters. Rare variants cause monogenic Proteus syndrome and contribute to Cowden-like syndrome.