MAPT

Chr 17ADMultiAR

microtubule associated protein tau

Also known as: DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1, MTBT2, PPND

NCBI Gene: 4137ENSG00000186868UniProt: P10636OMIM: 157140

This gene encodes tau protein, which promotes microtubule assembly and stability in neurons and functions as a linker between axonal microtubules and neural plasma membrane components. Mutations cause frontotemporal dementia with or without parkinsonism, progressive supranuclear palsy, and Pick disease, following autosomal dominant inheritance. The gene shows relatively low constraint against loss-of-function variants (LOEUF 0.57), and these disorders typically present in adulthood as neurodegenerative conditions affecting movement and cognition.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/Multi/ARLOEUF 0.575 OMIM phenotypes
Clinical Summary— MAPT
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 217 VUS of 500 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — MAPT
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.006
Z-score 3.28
OE 0.33 (0.20–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.52Z-score
OE missense 0.80 (0.74–0.87)
380 obs / 473.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.20–0.57)
0≤0.351.4
Missense OE0.80 (0.74–0.87)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 9 / 27.6Missense obs/exp: 380 / 473.1Syn Z: 0.02
DN
0.5966th %ile
GOF
0.6248th %ile
LOF
0.56top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOF1 literature citation
LOF1 literature citation

Literature Evidence

GOFThus, the R5L mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism.PMID:12325083
LOFTau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expressionPMID:28424350

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic12
VUS217
Likely Benign158
Benign55
Conflicting24
24
Pathogenic
12
Likely Pathogenic
217
VUS
158
Likely Benign
55
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
23
0
24
Likely Pathogenic
0
6
6
0
12
VUS
6
163
46
2
217
Likely Benign
0
24
44
90
158
Benign
0
3
48
4
55
Conflicting
—24
Total619716796490

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MAPT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
DementiaCognitive DeclineAlzheimer Disease

Investigating Neurocognitive Disorders Epidemiology

RECRUITING
NCT06375213King Chulalongkorn Memorial HospitalStarted 2023-08-24
Plasma tau phosphorylated at Thr217Neurocognitive examination
Mild Cognitive Impairment (MCI)AgingOral Microbiome

Elderberry Functional Gum and Cognitive & Oral Health in Older Adults

NOT YET RECRUITING
NCT07054645Phase NABurdur Mehmet Akif Ersoy UniversityStarted 2025-11-01
Elderberry Anthocyanin Chewing GumPlacebo Chewing Gum
Alzheimer DiseaseInactivityPreventive Therapy

The Link Between Physical Activity and Brain Health in Healthy Adults

RECRUITING
NCT07025070Technical University of MadridStarted 2024-11-25
Huntington's Disease (HD)

Biology-Driven Cognitive Profiling in Huntington's Disease

ACTIVE NOT RECRUITING
NCT07503743Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauStarted 2021-09-01
Frontotemporal Lobar Degeneration (FTLD)Progressive Supranuclear Palsy (PSP)Corticobasal Degeneration (CBD)

ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)

RECRUITING
NCT04363684Mayo ClinicStarted 2020-03-01
Parkinson DiseaseGBA Gene MutationGaucher Disease

The GBA Multimodal Study in Parkinson's Disease

RECRUITING
NCT04101968Pacific Parkinson's Research CentreStarted 2019-05-01
PET scanneuroQWERTY
Frontotemporal Lobar DegenerationAlzheimer DiseaseCognitively Normal

PET Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Using [18F]-PI-2620

RECRUITING
NCT05456503Phase PHASE3University of PennsylvaniaStarted 2022-09-19
[18F]-PI-2620
Concussion, BrainMild Traumatic Brain Injury

Risk Stratification in Children With Concussion

RECRUITING
NCT05825027Duke UniversityStarted 2023-05-23
COVID-19

A Two Year Longitudinal Clinical Study of Neurocognitive and Psychiatric Symptoms in Post COVID-19 Patients

ACTIVE NOT RECRUITING
NCT06298006Region Örebro CountyStarted 2022-02-22
Follow-up
Parkinson Disease

Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson's Disease

ACTIVE NOT RECRUITING
NCT04553185University of ExeterStarted 2018-11-28
Study procedure
Neurodegenerative DisordersParkinson DiseaseAlzheimer Disease

An Innovative Method in SAliva Samples for the Early Differential Diagnosis of High-impact NeuroDegenerative Diseases Through Raman Spectroscopy

ENROLLING BY INVITATION
NCT06875739Fondazione Don Carlo Gnocchi OnlusStarted 2025-02-14
Neurodegenerative DiseaseBehavioral Variant Frontotemporal Dementia (bvFTD)Primary Progressive Aphasia(PPA)

Tracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases

ENROLLING BY INVITATION
NCT07567664Phase NAIRCCS San RaffaeleStarted 2017-06-01
3 Tesla MRI without contrast mediumBlood sample for genetic analysisCerebrospinal fluid sampling (CSF)
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Multi-omic phenotyping of MAPT V337M neurons reveals early changes in axonogenesis and tau phosphorylation.
Mohl GA et al.·NPJ Dement
2026
NDST3 suppression restores lysosomal acidification and ameliorates amyloid-β and MAPT/tau pathology in Alzheimer's disease.
Ge C et al.·Transl Neurodegener
2026Open Access
Generation of three hiPSC clones from a frontotemporal dementia (FTD) patient with a heterozygous MAPT mutation p.K298_H299insQ (c.896_897insACA).
Hirose T et al.·Stem Cell Res
2026
CCL18 binding to MAPT promotes chronic obstructive pulmonary disease by inhibiting autophagy and triggering cell senescence.
Chen H et al.·Tissue Cell
2026
Differential genome-wide association analysis of schizophrenia and post-traumatic stress disorder identifies opposing effects at the MAPT/CRHR1 locus.
Cheng ZS.·Front Genet
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients