GeneBe

MAPT

protein-coding

microtubule associated protein tau, the group of Protein phosphatase 1 regulatory subunits

Gene summary

This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy. [provided by RefSeq, Jul 2008]

Previous symbols:
  • DDPAC
  • MAPTL

MANE transcript

NM_001377265.1

Inheritance

AD, AR

ClinVar variants

P:33U:183B:143

Top phenotype

Supranuclear palsy, progressive, 1; Frontotemporal dementia 1; Parkinson-dementia syndrome; Pick disease

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr17:45,894,527-46,028,334

External References & Databases

Ensembl (ENSG00000186868)NCBI Gene (4137)OMIM (157140)HGNC:6893GenCCUniProt (P10636)AlphaFoldClinVar (MAPT)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~133.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Pick diseaseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008243

Submitter: Genomics England PanelApp

progressive supranuclear palsy-parkinsonism syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009839

Submitter: Labcorp Genetics (formerly Invitae)

supranuclear palsy, progressive, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010997

Submitter: Genomics England PanelApp

late-onset Parkinson diseaseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008199

Submitter: Genomics England PanelApp

progressive supranuclear palsy-parkinsonism syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009839

Submitter: Genomics England PanelApp

semantic dementiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010857

Submitter: Genomics England PanelApp

Pick diseaseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008243

Submitter: Labcorp Genetics (formerly Invitae)

late-onset Parkinson diseaseLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0008199

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Supranuclear palsy, progressive, 1; Frontotemporal dementia 1; Parkinson-dementia syndrome; Pick diseaseAD/AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 1416801; 7936288; 7936241; 7977375; 9029080; 9781517; 9789048; 10202939; 9443491; 9641683; 9708963; 9932968; 10072441; 10412802; 10534245; 10388790; 11134398; 11117542; 11445645; 11710889; 11601501; 11220749; 12177383; 12056930; 14595660; 12913211; 14991829; 15792962; 16195395; 10388790; 16278856; 17923640; 17310038; 18703462; 19884571; 19884572; 19786698; 21295377; 21555888; 21558644; 21943955; 22109955; 22482453; 22699846Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAPT variants in ClinVar

23 Conditions Cataloged
Frontotemporal dementiaTotal: 277
not providedTotal: 202
not specifiedTotal: 60
MAPT-related disorderTotal: 58
MAPT-Related Spectrum DisordersTotal: 25
Inborn genetic diseasesTotal: 24
Pick diseaseTotal: 19
Supranuclear palsy, progressive, 1Total: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001377265.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
5
clinvar
103
clinvar
3
clinvar
 113
missense
17
clinvar
14
clinvar
166
clinvar
33
clinvar
3
clinvar
 233
nonsense
3
clinvar
1
clinvar
 4
start loss
0
frameshift
6
clinvar
 6
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total18151831376359

Highest pathogenic variant AF is 0.000034105396

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 100 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001377265.1RefSeqNP_001364194.112MANE Select
ENST00000262410.10EnsemblENSP00000262410.612MANE Select
NM_001123066.4RefSeqNP_001116538.214Standard
NM_001123067.4RefSeqNP_001116539.110Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Alzheimer,s disease - Homo sapiens (human)
  • MAPK signaling pathway - Homo sapiens (human)
  • Taxane Pathway, Pharmacokinetics
  • IL-5 Signaling Pathway
  • Regulation of Microtubule Cytoskeleton

Biological Process

  • microtubule cytoskeleton organization
  • microglial cell activation
  • internal protein amino acid acetylation
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • cell-cell signaling

Molecular Function

  • DNA binding
  • AT DNA binding
  • double-stranded DNA binding
  • single-stranded DNA binding
  • RNA binding

Cellular Component

  • extracellular region
  • nucleus
  • cytoplasm
  • mitochondrion
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000344290
Coding exons
14
Length
133953
Individuals with no LoFs
125737
Homozygous LoFs
0
Heterozygous LoFs
11
Defined
125748
p
0.0000437
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.523804730.8030.00003004959
Missense (PolyPhen)110172.950.636041803
Synonymous0.01572042040.9990.00001521652
Loss of Function3.28927.60.3260.00000136357

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.0000550.000054rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000260.000018rare
South Asian0.000140.00013rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N- terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311}.;
Disease
DISEASE: Note=In Alzheimer disease, the neuronal cytoskeleton in the brain is progressively disrupted and replaced by tangles of paired helical filaments (PHF) and straight filaments, mainly composed of hyperphosphorylated forms of TAU (PHF-TAU or AD P- TAU). O-GlcNAcylation is greatly reduced in Alzheimer disease brain cerebral cortex leading to an increase in TAU/MAPT phosphorylations. {ECO:0000269|PubMed:14517953, ECO:0000269|PubMed:26086902}.; DISEASE: Frontotemporal dementia (FTD) [MIM:600274]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269|PubMed:10208578, ECO:0000269|PubMed:10214944, ECO:0000269|PubMed:10374757, ECO:0000269|PubMed:10489057, ECO:0000269|PubMed:10553987, ECO:0000269|PubMed:10802785, ECO:0000269|PubMed:11071507, ECO:0000269|PubMed:11117541, ECO:0000269|PubMed:11278002, ECO:0000269|PubMed:11585254, ECO:0000269|PubMed:11889249, ECO:0000269|PubMed:11906000, ECO:0000269|PubMed:11921059, ECO:0000269|PubMed:12473774, ECO:0000269|PubMed:12509859, ECO:0000269|PubMed:14517953, ECO:0000269|PubMed:15883319, ECO:0000269|PubMed:16240366, ECO:0000269|PubMed:26086902, ECO:0000269|PubMed:9629852, ECO:0000269|PubMed:9641683, ECO:0000269|PubMed:9736786, ECO:0000269|PubMed:9789048, ECO:0000269|PubMed:9973279}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pick disease of the brain (PIDB) [MIM:172700]: A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration. {ECO:0000269|PubMed:10604746, ECO:0000269|PubMed:11089577, ECO:0000269|PubMed:11117542, ECO:0000269|PubMed:11601501, ECO:0000269|PubMed:11891833}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in MAPT are a cause of corticobasal degeneration (CBD). It is marked by extrapyramidal signs and apraxia and can be associated with memory loss. Neuropathologic features may overlap Alzheimer disease, progressive supranuclear palsy, and Parkinson disease.; DISEASE: Progressive supranuclear palsy 1 (PSNP1) [MIM:601104]: Characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613. {ECO:0000269|PubMed:10534245, ECO:0000269|PubMed:11220749, ECO:0000269|PubMed:12325083, ECO:0000269|PubMed:14991828, ECO:0000269|PubMed:14991829, ECO:0000269|PubMed:16157753}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Parkinson-dementia syndrome (PARDE) [MIM:260540]: A syndrome characterized by parkinsonism, tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.927

Intolerance Scores

LoFtool
0.0668
RVIS EVS
2.18
RVIS percentile EVS
98.09

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.850

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyHighMediumHigh
CancerHighHighHigh
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