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 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]

GeneReviewsOMIMResearchGenerating clinical summary…
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
38 unique Pathogenic / Likely Pathogenic· 258 VUS of 610 total submissions
💊
Clinical Trials
11 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 ↗

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 OE?0.33 (0.20–0.57)
0≤0.351.4
Missense OE?0.80 (0.74–0.87)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 9 / 27.6Missense obs/exp: 380 / 473.1Syn Z: 0.02

This gene — mechanism propensity

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 · 71% of P/LP are missense
LOF1 literature citation

Literature Evidence

GOFThus, the R5L mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism.1
LOFTau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 12325083 ↗
  2. 2.PMID 28424350 ↗

ClinVar Variant Classifications

610 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic12
VUS258
Likely Benign170
Benign94
Conflicting31
26
Pathogenic
12
Likely Pathogenic
258
VUS
170
Likely Benign
94
Benign
31
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
18
6
1
26
Likely Pathogenic
0
9
2
1
12
VUS
10
174
72
2
258
Likely Benign
0
25
47
98
170
Benign
0
11
73
10
94
Conflicting
—31
Total11237200112591

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

View in ClinVar →

59 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap MAPT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MAPT · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
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
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
Alzheimer DiseaseInactivityPreventive Therapy

The Link Between Physical Activity and Brain Health in Healthy Adults

RECRUITING
NCT07025070Technical University of MadridStarted 2024-11-25
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
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
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 ETSStarted 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)
DementiaCognitive DeclineAlzheimer Disease

Investigating Neurocognitive Disorders Epidemiology

RECRUITING
NCT06375213King Chulalongkorn Memorial HospitalStarted 2023-08-24
Plasma tau phosphorylated at Thr217Neurocognitive examination

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