AtlasWho We HelpOur ScienceProductsOutcomes
Log InAskSequence your genome↗
Gene
PIK3CA
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
- HGNC 8975↗(opens in a new tab)
- Ensembl gene ENSG00000121879↗(opens in a new tab)
- NCBI Gene 5290↗(opens in a new tab)
Summary
- Cytogenetic location
- 3q26.32
- Coordinates
- Chromosome 3: 179,148,357–179,240,093 (GRCh38)
- Exons
- 21 exons across 91.7 kb
- Protein
- 1,068 amino acids, 124.3 kDa
- Also known as
- PI3K
- MANE Select transcript
- ENST00000263967.4NM_006218.4
- Locus type
- Protein-coding
- Very high
- Confident
- Low
- Very low
AtlasWho We HelpOur ScienceProductsOutcomes
Log InAskSequence your genome↗
Share this page
This page as data
Add .json to the page's address, or ask for application/json, to read it as JSON.
library(jsonlite)
url <- "https://dantelabs.com/genes/pik3ca.json"
page <- fromJSON(url)
page$gene$namePIK3CA3q26.32
AtlasWho We HelpOur ScienceProductsOutcomes
Log InAskSequence your genome↗
Read PIK3CA, and the rest of your genome, with one test.
From $449Free shipping · Results in 6–8 weeks
Get my Genome TestCurated report relevant to this gene
MTOR Pathway Megalencephaly and Overgrowth Disorders
- Overgrowth and Cerebral Malformations due to MTOR Pathway Gene Changes
Caused by activating changes in AKT3, MTOR, PIK3CA or PIK3R2, genes of the PI3K-AKT-MTOR growth pathway. Changes either arise de novo in one copy of the gene in every cell, or after conception so that only some cells are affected (mosaicism).
- 5 GenCC submitters rate it definitive or strong
▶Actionability
Care involves brain imaging and monitoring for hydrocephalus, epilepsy treatment, which sometimes includes surgery, and developmental support. Alpelisib is approved for reducing overgrowth in PIK3CA-related overgrowth, but it is not known whether it helps the brain features. Most cases arise new, so recurrence risk is usually low, but genetic counselling is recommended.
How PIK3CA is laid out
- Coding sequence
- Untranslated region
- Intron
- Direction of transcription
- Known disease-causing sites
- Stretches short reads find hard
- Variants with a page
Exons of the gene's MANE Select transcript (release v1.5), from NCBI and EMBL-EBI, on the GRCh38 reference genome.
Chromosome bands from UCSC's GRCh38 ideogram (2022-10-29).
Nearby genes from Ensembl release 116, on GRCh38.
Exons make up 9.3 kb of the gene's 91.7 kb; 3,207 of those bases code for the protein.
Sequencing PIK3CA
45Hard
How hard PIK3CA is to sequence with short reads, out of 100
0 · Easy100 · Hard
Much of PIK3CA sits where short reads can miss or misplace a change.
What adds to it: the share of PIK3CA's exons in each kind of hard region
- MappabilityStretches where 100 or 250 bp reads cannot be placed uniquely, so a call there may be missing or wrong. On its own, a gene wholly in this kind of region would score 100.27%
- HomologySegmental duplications: copies elsewhere in the genome, such as paralogues and pseudogenes, at 90% identity or more. On its own, a gene wholly in this kind of region would score 60.37%
- Shared with chrYThe pseudoautosomal regions and the X-transposed region, where chrX and chrY carry the same or nearly the same sequence, so a read from one may be placed on the other. On its own, a gene wholly in this kind of region would score 60.0%
- Reference coverageGaps in the reference assembly nearby, where there is no sequence for reads to align to. On its own, a gene wholly in this kind of region would score 50.0%
- RepeatsTandem repeats and runs of one base, which reads slip on and may not span. On its own, a gene wholly in this kind of region would score 30.5.6%
- GC contentWindows under 25% or over 65% G and C, which library preparation covers thinly. On its own, a gene wholly in this kind of region would score 20.9.6%
A Dante Labs score from our own research, built on NIST's Genome in a Bottle maps of hard-to-sequence regions.How it's scoredEach bar is the share of PIK3CA's exon bases in that kind of difficult region. Any one kind can make a gene hard on its own, and each further kind adds less: 0 when no base is in any, 100 when every base is where reads cannot be placed uniquely.
73
positions in PIK3CA where ClinVar classes a change as pathogenic or likely pathogenic
11 of them (15%) fall in regions short reads find hard.
- Low mappabilityRegions where 100 bp or 250 bp reads cannot be placed uniquely. (11 sites)
- Segmental duplicationsCopies of at least 1 kb sharing at least 90% identity with another part of the genome (paralogues, pseudogenes); reads may align to the wrong copy. (11 sites)
A whole genome covers all 91.7 kb of PIK3CA, introns included, not only the 9.3 kb of exons.
Variants with a page (5)
The PIK3CA variants with a page here, most review stars first. Each page describes ClinVar's public record of the variant, never a result.
| Variant | HGVS c. | Exon or intron | Position (GRCh38) | ClinVar classification | Review status |
|---|---|---|---|---|---|
| E110del | c.328_330del | Exon 2 | 179,199,149 | Likely pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| E542K | c.1624G>A | Exon 10 | 179,218,294 | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| E726K | c.2176G>A | Exon 14 | 179,221,146 | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| G914R | c.2740G>A | Exon 19 | 179,230,077 | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| H1047R | c.3140A>G | Exon 21 | 179,234,297 | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
ClinVar pathogenic variants (90)
The PIK3CA variants ClinVar classifies pathogenic or likely pathogenic for any condition, reviewed by at least one submitter with criteria, and the most reviewed of them. It is ClinVar's public record of the gene, never a result.
- Pathogenic 42
- Pathogenic/likely pathogenic 7
- Likely pathogenic 41
| Variant | Conditions | ClinVar classification | Review status |
|---|---|---|---|
| NM_006218.4(PIK3CA):c.1624G>A (p.Glu542Lys) | overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| NM_006218.4(PIK3CA):c.2176G>A (p.Glu726Lys) | overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| NM_006218.4(PIK3CA):c.2740G>A (p.Gly914Arg) | overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg) | overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | Pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| NM_006218.4(PIK3CA):c.325GAA[1] (p.Glu110del) | overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | Likely pathogenic | ★★★★3 stars out of 4 reviewed by expert panel |
| NM_006218.4(PIK3CA):c.263G>A (p.Arg88Gln) | Cowden disease and 3 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.353G>A (p.Gly118Asp) | Cowden disease and 2 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1030G>A (p.Val344Met) | Cowden disease and 2 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1048G>A (p.Asp350Asn) | PIK3CA-related overgrowth spectrum | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1090G>A (p.Gly364Arg) | PIK3CA-related overgrowth spectrum and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1133G>A (p.Cys378Tyr) | Cowden disease and 3 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys) | CLOVES syndrome and 3 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) | CLOVES syndrome and 3 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1635G>T (p.Glu545Asp) | Cowden disease and 1 other | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr) | CLAPO syndrome and 15 others | Pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.323G>A (p.Arg108His) | Cowden disease and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.344G>C (p.Arg115Pro) | PIK3CA-related overgrowth spectrum | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1345C>A (p.Pro449Thr) | megalencephaly-capillary malformation-polymicrogyria syndrome | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.1637A>C (p.Gln546Pro) | PIK3CA-related overgrowth spectrum | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.2816A>G (p.Asp939Gly) | megalencephaly-capillary malformation-polymicrogyria syndrome | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.3012G>A (p.Met1004Ile) | PIK3CA-related overgrowth spectrum | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.3061T>C (p.Tyr1021His) | Cowden disease and 1 other | Pathogenic/likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.277C>T (p.Arg93Trp) | PIK3CA-related overgrowth spectrum and 1 other | Likely pathogenic | ★★★★2 stars out of 4 criteria provided, multiple submitters, no conflicts |
| NM_006218.4(PIK3CA):c.241G>A (p.Glu81Lys) | CLOVES syndrome and 2 others | Pathogenic | ★★★★1 star out of 4 criteria provided, single submitter |
| NM_006218.4(PIK3CA):c.278G>A (p.Arg93Gln) | Cowden syndrome 5 | Pathogenic | ★★★★1 star out of 4 criteria provided, single submitter |
See all 90 with every other PIK3CA variant in ClinVar → (opens in a new tab)
Genes linked to the same conditions
Traits linked to PIK3CA
The Human Phenotype Ontology lists these as features of the rare conditions PIK3CA can cause. Each trait's page lists the other genes linked to it.
Abnormality of the nervous system
- Epilepsy
- Glioblastoma multiforme
- Headache
- Hyperintensity of cerebral white matter on MRI
- Interictal EEG abnormality
- Intracranial meningioma
- Abnormal brain FDG positron emission tomography
- Abnormal shape of nervous system
Show 84 more traits
- Absent/small cerebellum
- Anxiety
- Attention deficit
- Behavioral abnormality
- Depression
- EEG with burst suppression
- EEG with focal sharp slow waves
- EEG with focal spikes
- EEG with polyspike wave complexes
- Focal cortical dysplasia
- Focal motor seizure
- Focal T2 hyperintense brainstem lesion
- Focal T2 hypointense brainstem lesion
- Focal T2 hypointense thalamic lesion
- Global developmental delay
- Hemihypsarrhythmia
- Hemimegalencephaly
- Intellectual disability
- Irritability
- Migraine
- More grooves in brain
- Nerve tumor
- Numbness
- Pins and needles feeling
- Rise in pressure inside skull
- Seizure affecting one half of brain
- Too much cerebrospinal fluid in the brain
- Ventriculomegaly
- Abnormal central motor function
- Abnormal central sensory function
- Abnormal gait
- Abnormal neuron shape
- Abnormal pyramidal sign
- Abnormal social behavior
- Abnormal speech pattern
- Abnormality of the cerebellum
- Aplasia/Hypoplasia of the corpus callosum
- Ataxia
- Benign neoplasm of the central nervous system
- Cancer of early nerve cells
- Chiari malformation
- Cognitive impairment
- Cranial nerve paralysis
- Difficulty articulating speech
- Difficulty sleeping
- Disorder of involuntary muscle movements
- Disturbed sensory perception
- Dysgraphia
- Epileptic spasm
- Fewer and broader ridges in brain
- Focal tonic seizure
- Gliosis
- Gray matter heterotopia
- Hallucinations
- Intellectual disability, mild
- Intellectual disability, severe
- Jerking
- Loss of developmental milestones
- Memory impairment
- Meningocele
- Multiple mucosal neuromas
- Myelomeningocele
- Paralysis or weakness of one side of body
- Pauses in breathing while sleeping
- Repeated seizures without recovery between them
- Spinal cord lesion
- Spinal dysraphism
- Spinal meningioma
- Split spine
- Sudden loss of muscle tone
- Tethered cord
- Trigeminal neuralgia
- Weakness of one side of body
- Astrocytoma
- Brain stem compression
- Can't control feelings
- Excessive daytime sleepiness
- Ganglioneuroma
- Noncancerous growth of membranes covering brain
- Spasms on one side of the face
- Transient global amnesia
- Cavum septum pellucidum
- Enlarged brain
- Intention tremor
Abnormality of head or neck
- Capillary malformation of the lip
- Dimple chin
- Enlargement of half of face
- Facial asymmetry
- Adenoma sebaceum
- Big calvaria
- Narrow eyelid opening
- Wide mouth
Show 34 more traits
- Abnormality of head shape
- Abnormality of the skull
- Abnormally large tongue
- Big lower jaw
- Big maxilla
- Deviated nasal septum
- Early eruption of teeth
- Enlargement of parotid gland
- Frontal bossing
- Full cheeks
- High forehead
- Prominence of cheekbone
- Abnormality of the sense of smell
- Abnormally small head
- Absence of adult teeth
- Adhesion of the temporomandibular joint
- Bad bite
- Bell's palsy
- Cancer of salivary gland
- Depressed nasal bridge
- Increased size of tooth
- Webbed neck
- Neoplasm of the tongue
- Broad forehead
- Decreased size of maxilla
- Downward slanting of the opening between the eyelids
- Enlargement of skull bones
- Eye folds
- Grooved tongue
- High palate
- Little lower jaw
- Narrow mouth
- Progressively abnormally enlarging cranium
- Smooth philtrum
Abnormality of the cardiovascular system
- Cerebral cavernous malformation
- Strawberry birthmark
- Venous malformation
- Arteriovenous malformation
- Lymphangioma
- Poorly functioning veins
- Strawberry mark
- Telangiectasia of the skin
Show 27 more traits
- Visceral angiomatosis
- Abnormal lymphatic vessel morphology
- Abnormality of the cerebral blood vessels
- Blood clot in artery of lung
- Collection of dilated blood vessels that forms mass
- Cutis marmorata
- Enlarged tonsils
- Varicose veins
- Vascular skin abnormality
- Abnormal cardiovascular system morphology
- Abnormal heart rate
- Abnormal tricuspid valve morphology
- Abnormal vein
- Abnormality of lung artery
- Abnormality of the lymphatic system
- An opening in the wall separating the top two chambers of the heart
- Cardiac diverticulum
- Cardiac failure
- Choroidal hemangioma
- Disruption of blood oxygen supply to brain
- Increased spleen size
- Patent ductus arteriosus
- Peripheral arteriovenous fistula
- Retinal cavernous hemangioma
- Fainting spell
- Abnormality of the cardiovascular system
- Hole in heart wall separating two lower heart chambers
Abnormality of the endocrine system
- Decreased circulating ACTH concentration
- Decreased circulating follicle stimulating hormone concentration
- Decreased circulating luteinizing hormone level
- Decreased serum estradiol
- Decreased serum testosterone level
- Hypogonadotropic hypogonadism
- Increased circulating prolactin concentration
- Low blood cortisol level
Show 16 more traits
- Low thyroid gland function due to abnormal pituitary gland
- Secondary growth hormone deficiency
- Abnormal hypothalamus physiology
- Enlarged pituitary gland
- Hypothalamic hypothyroidism
- Neoplasm of the anterior pituitary
- Neoplasm of the thyroid gland
- Noncancerous tumor in pituitary gland
- Reduced circulating prolactin concentration
- Adrenal calcification
- Neoplasm of the posterior pituitary
- Enlarged thyroid gland in neck
- Overactive thyroid
- Thyroid adenoma
- Thyroid gland inflammation
- Underactive thyroid
Abnormality of the genitourinary system
- Abnormal absence of menstruation
- Difficulty getting a full erection
- Small kidneys
- Abnormality of the menstrual cycle
- Absent/small kidney
- Cystic kidney disease
- Endometrial carcinoma
- Enlarged kidney
Show 16 more traits
- Epididymal cyst
- Hydrocele testis
- Kidney cancer
- Malignant genitourinary tract tumor
- Nephroblastoma
- Ovarian cancer
- Ovarian serous cystadenoma
- Testicular lipomatosis
- Urinary tract neoplasm
- Loss of bladder control
- Cancer starting in small tubes in kidneys
- Dysgerminoma
- Ovarian cyst
- Ovarian papillary adenocarcinoma
- Transitional cell carcinoma of the bladder
- Uterine leiomyosarcoma
Abnormality of limbs
- Asymmetric overgrowth
- Finger overgrowth
- Left and right leg differ in length or width
- Duplication of bones of the toes
- Extra finger
- Finger syndactyly
- Fused toes
- Unequal size of arms
Show 14 more traits
- Broad palm
- Bulbous tips of toes
- Gap between 1st and 2nd toes
- Overgrowth of one arm
- Overgrowth of one leg
- Ulnar deviation of the hand
- Cutaneous syndactyly
- Decreased arm strength
- Dislocated kneecap
- Lower limb muscle weakness
- More than five fingers or toes on hands or feet
- Webbed 2nd-4th toes
- Thickening of the outer layer of the skin of the palms and soles
- Webbed fingers or toes
Abnormality of the digestive system
- Abdominal pain
- Constipation
- Malabsorption
- Colon cancer
- Nausea and vomiting
- Rectal tumor
- Stomach tumor
- Accumulation of fluid in the abdomen
Show 13 more traits
- Cancer of the pancreas
- Enlarged liver
- Episodic vomiting
- Growths in inner lining of intestine
- Hepatocellular carcinoma
- Liver cancer
- Pancreatic adenocarcinoma
- Colonic diverticula
- Hamartomatous polyposis
- Hereditary nonpolyposis colorectal carcinoma
- Micronodular cirrhosis
- Stomach cancer
- Subacute progressive viral hepatitis
Abnormality of blood and blood-forming tissues
- Bleeding in brain
- Gastrointestinal bleeding
- Blood clot in vein
- Abnormal blood clot
- Blood tumor
- Hypercoagulability
- Internal bleeding
- Microcytic anemia
Show 2 more traits
External links
Gene records
Transcript
Protein
Where this comes from
- HGNC: the gene's symbol, name, other symbols and location.
- MANE Select v1.5, from NCBI and EMBL-EBI: the transcript, its exons and coding sequence.
- GenCC and ClinGen, released 2026-10-21: which conditions the gene is linked to, and how strongly.
- The ACMG secondary findings list, SF v3.2.
- ClinVar and the GIAB stratifications: known disease-causing sites, and the regions short reads find hard.
- The Genome in a Bottle genome stratifications, from NIST: the sequencing difficulty score.
- The Human Phenotype Ontology, release 2026-09-01: the traits linked to the gene. Find out more at hpo.jax.org.
- Data release 2026.10.21-c791e85a.
Cite this page
Dante Labs. (n.d.). PIK3CA gene: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. Retrieved 23 October 2026, from https://dantelabs.com/genes/pik3ca
Dante Labs. PIK3CA gene: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [Internet]. [cited 23 October 2026]. Available from: https://dantelabs.com/genes/pik3ca
AtlasWho We HelpOur ScienceProductsOutcomes
Log InAskSequence your genome↗
One test. A lifetime of answers.
From $449Free shipping · Results in 6–8 weeks