MAPT

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

Basic information

Region (hg38): 17:45894526-46028334

Previous symbols: [ "DDPAC", "MAPTL" ]

Links

ENSG00000186868 ∙ NCBI:4137 ∙ OMIM:157140 ∙ HGNC:6893 ∙ Uniprot:P10636 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• supranuclear palsy, progressive, 1 (Strong), mode of inheritance: AD
• late-onset Parkinson disease (Strong), mode of inheritance: AD
• Pick disease (Strong), mode of inheritance: AD
• semantic dementia (Strong), mode of inheritance: AD
• progressive supranuclear palsy-parkinsonism syndrome (Moderate), mode of inheritance: AR
• Pick disease (Strong), mode of inheritance: AD
• late-onset Parkinson disease (Limited), mode of inheritance: Unknown
• progressive supranuclear palsy-parkinsonism syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Supranuclear palsy, progressive, 1; Frontotemporal dementia; Parkinson-dementia syndrome; Pick disease	AD/AR	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	Neurologic	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; 22699846

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAPT gene.

• Frontotemporal dementia (208 variants)
• not provided (200 variants)
• MAPT-Related Spectrum Disorders (145 variants)
• Syndromic intellectual disability (27 variants)
• not specified (24 variants)
• Inborn genetic diseases (12 variants)
• MAPT-related condition (10 variants)
• Pick disease (4 variants)
• Frontotemporal dementia;Supranuclear palsy, progressive, 1;Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Pick disease (3 variants)
• Progressive supranuclear ophthalmoplegia;Pick disease;Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Frontotemporal dementia (2 variants)
• Parkinson disease, late-onset (2 variants)
• Progressive supranuclear ophthalmoplegia (2 variants)
• Supranuclear palsy, progressive, 1;Frontotemporal dementia;Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Pick disease (2 variants)
• Frontotemporal dementia;Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Pick disease;Supranuclear palsy, progressive, 1 (1 variants)
• Alzheimer disease (1 variants)
• Progressive supranuclear ophthalmoplegia;Frontotemporal dementia;Pick disease (1 variants)
• Early-onset dementia of unclear type (1 variants)
• Progressive supranuclear ophthalmoplegia;Frontotemporal dementia;Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Pick disease (1 variants)
• Pick disease;Supranuclear palsy, progressive, 1;Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Frontotemporal dementia (1 variants)
• Pick disease;Progressive supranuclear palsy-parkinsonism syndrome;Parkinson disease, late-onset;Frontotemporal dementia;Supranuclear palsy, progressive, 1 (1 variants)
• Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Pick disease;Frontotemporal dementia;Supranuclear palsy, progressive, 1 (1 variants)
• Frontotemporal dementia;Memory impairment;Mental deterioration (1 variants)
• Multiple system atrophy (1 variants)
• Supranuclear palsy, progressive, 1 (1 variants)
• Progressive supranuclear palsy-parkinsonism syndrome (1 variants)
• Dementia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPT 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	1		4	78	8	91
missense	7	8	93	21	12	141
nonsense			1			1
start loss						0
frameshift			4			4
inframe indel	1					1
splice donor/acceptor (+/-2bp)						0
splice region		2	4	1		7
non coding	2	2	70	50	83	207
Total	11	10	172	149	103

Highest pathogenic variant AF is 0.0000131

Variants in MAPT

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

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

Position	Type	Phenotype	Significance	ClinVar
17-45894527-G-C		MAPT-Related Spectrum Disorders	Uncertain significance (Jan 13, 2018)
17-45894541-G-T		MAPT-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
17-45894563-G-A		MAPT-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
17-45894571-C-A		MAPT-Related Spectrum Disorders	Benign (Jan 12, 2018)
17-45894659-TC-T		MAPT-Related Spectrum Disorders	Benign (Jun 14, 2016)
17-45894678-G-T		MAPT-Related Spectrum Disorders	Uncertain significance (Jan 13, 2018)
17-45894810-C-G		Frontotemporal dementia	Benign (Jan 19, 2024)
17-45961999-C-T			Benign (Aug 10, 2018)
17-45962044-A-G			Benign (Aug 11, 2018)
17-45962106-C-T			Likely benign (Sep 26, 2018)
17-45962150-G-T			Benign (Aug 11, 2018)
17-45962325-A-G		not specified • MAPT-Related Spectrum Disorders	Benign (Aug 11, 2018)
17-45962341-G-T		Frontotemporal dementia	Uncertain significance (Apr 18, 2022)
17-45962347-C-A		Frontotemporal dementia • Supranuclear palsy, progressive, 1;Frontotemporal dementia;Parkinson disease, late-onset;Progressive supranuclear palsy-parkinsonism syndrome;Pick disease	Uncertain significance (Nov 04, 2021)
17-45962350-C-T		MAPT-Related Spectrum Disorders • Frontotemporal dementia	Conflicting classifications of pathogenicity (Jun 27, 2022)
17-45962351-G-A		Frontotemporal dementia • MAPT-Related Spectrum Disorders	Conflicting classifications of pathogenicity (Mar 21, 2022)
17-45962351-G-T		Supranuclear palsy, progressive, 1	Pathogenic (Sep 13, 2017)
17-45962355-G-A		Frontotemporal dementia	Likely benign (Nov 21, 2020)
17-45962362-G-A		Frontotemporal dementia	Uncertain significance (Sep 14, 2022)
17-45962368-A-C		Frontotemporal dementia	Uncertain significance (Apr 12, 2022)
17-45962373-A-G		Frontotemporal dementia	Likely benign (Sep 14, 2021)
17-45962376-T-C		Frontotemporal dementia	Likely benign (Aug 30, 2022)
17-45962379-C-T		Frontotemporal dementia	Likely benign (Oct 13, 2023)
17-45962384-G-T		Parkinson disease, late-onset • Frontotemporal dementia • Progressive supranuclear ophthalmoplegia • Pick disease	Uncertain significance (Feb 11, 2019)
17-45962387-C-T		Frontotemporal dementia	Benign/Likely benign (Oct 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPT	protein_coding	protein_coding	ENST00000344290	14	133953

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00603	0.994	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.52	380	473	0.803	0.0000300	4959
Missense in Polyphen		110	172.95	0.63604		1803
Synonymous	0.0157	204	204	0.999	0.0000152	1652
Loss of Function	3.28	9	27.6	0.326	0.00000136	357

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000554	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000176
Middle Eastern	0.0000554	0.0000544
South Asian	0.000137	0.000131
Other	0.000163	0.000163

dbNSFP

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.
• Pathway: Alzheimer,s disease - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Taxane Pathway, Pharmacokinetics;IL-5 Signaling Pathway;Regulation of Microtubule Cytoskeleton;Alzheimers Disease;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Kit receptor signaling pathway;Copper homeostasis;MAPK Signaling Pathway;IL-2 Signaling Pathway;Notch Signaling Pathway;bioactive peptide induced signaling pathway;deregulation of cdk5 in alzheimers disease;Caspase-mediated cleavage of cytoskeletal proteins;Apoptotic cleavage of cellular proteins;Apoptotic execution phase;Apoptosis;Programmed Cell Death;LPA receptor mediated events;Reelin signaling pathway;Signaling mediated by p38-gamma and p38-delta;LKB1 signaling events (Consensus)

Recessive Scores

• pRec: 0.927

Intolerance Scores

• loftool: 0.0668
• rvis_EVS: 2.18
• rvis_percentile_EVS: 98.09

Haploinsufficiency Scores

• pHI: 0.271
• hipred: Y
• hipred_score: 0.565
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.850

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mapt
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye 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); 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; hematopoietic 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• 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;memory;response to lead ion;regulation of signaling receptor activity;regulation of autophagy;negative regulation of gene expression;negative regulation of mitochondrial membrane potential;rRNA metabolic process;axonal transport of mitochondrion;central nervous system neuron development;regulation of microtubule polymerization or depolymerization;regulation of microtubule polymerization;positive regulation of microtubule polymerization;cytoplasmic microtubule organization;neuron projection development;positive regulation of superoxide anion generation;regulation of chromosome organization;negative regulation of kinase activity;stress granule assembly;cellular response to heat;cellular response to reactive oxygen species;positive regulation of axon extension;microtubule polymerization;astrocyte activation;regulation of synaptic plasticity;intracellular distribution of mitochondria;generation of neurons;synapse organization;regulation of calcium-mediated signaling;protein complex oligomerization;axon development;regulation of microtubule cytoskeleton organization;plus-end-directed organelle transport along microtubule;regulation of mitochondrial fission;negative regulation of mitochondrial fission;supramolecular fiber organization;axonal transport;regulation of cellular response to heat;regulation of long-term synaptic depression;positive regulation of neuron death;positive regulation of protein localization to synapse;neurofibrillary tangle assembly;negative regulation of establishment of protein localization to mitochondrion;positive regulation of cellular protein localization;negative regulation of tubulin deacetylation;positive regulation of diacylglycerol kinase activity;amyloid fibril formation;cellular response to nerve growth factor stimulus;cellular response to brain-derived neurotrophic factor stimulus;regulation of response to DNA damage stimulus
• Cellular component: extracellular region;nucleus;cytoplasm;mitochondrion;cytosol;microtubule;plasma membrane;microtubule cytoskeleton;membrane;nuclear speck;axon;dendrite;growth cone;axolemma;nuclear periphery;cytoplasmic ribonucleoprotein granule;somatodendritic compartment;neuron projection;neuronal cell body;dendritic spine;cell body;main axon;membrane raft;tubulin complex;glial cell projection;neurofibrillary tangle;axon cytoplasm
• Molecular function: DNA binding;AT DNA binding;double-stranded DNA binding;single-stranded DNA binding;RNA binding;actin binding;protein binding;microtubule binding;SH3 domain binding;enzyme binding;protein kinase binding;protein binding, bridging;apolipoprotein binding;dynactin binding;phosphatidylinositol binding;identical protein binding;protein homodimerization activity;sequence-specific DNA binding;receptor ligand activity;chaperone binding;protein phosphatase 2A binding;Hsp90 protein binding;lipoprotein particle binding;histone-dependent DNA binding;microtubule lateral binding;phosphatidylinositol bisphosphate binding