MAP1B

Chr 5AD

microtubule associated protein 1B

NCBI Gene: 4131ENSG00000131711UniProt: P46821

Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing

Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 83MIM #619808
AD
Periventricular nodular heterotopia 9MIM #618918
AD
100
ClinVar variants
4
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MAP1B
🧬
Gene-Disease Validity (ClinGen)
periventricular nodular heterotopia · ADStrong

Strong evidence — appropriate for clinical testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 82 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.13LOEUF
pLI 1.000
Z-score 7.72
OE 0.06 (0.03–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.51Z-score
OE missense 0.80 (0.76–0.85)
1051 obs / 1306.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.03–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.76–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 5 / 79.1Missense obs/exp: 1051 / 1306.4Syn Z: -0.05

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic2
VUS82
Likely Benign14
2
Pathogenic
2
Likely Pathogenic
82
VUS
14
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
1
0
2
Likely Pathogenic
1
0
1
0
2
VUS
0
82
0
0
82
Likely Benign
0
10
1
3
14
Benign
0
0
0
0
0
Total29233100

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

View in ClinVar →

Protein Context — Lollipop Plot

MAP1B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Deafness, autosomal dominant 83

MIM #619808

Molecular basis of disorder known

Autosomal dominant

Periventricular nodular heterotopia 9

MIM #618918

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — MAP1B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genomic and phenotypic delineation of congenital microcephaly.
Shaheen R et al.·Genet Med
2019
Autoimmune Vestibulocerebellar Syndromes.
Narayan RN et al.·Semin Neurol
2020Review
Paraneoplastic neuropathies and peripheral nerve hyperexcitability disorders.
Shelly S et al.·Handb Clin Neurol
2024Review
Novel MAP1B loss-of-function variant associated with periventricular nodular heterotopia 9 and literature review on genotype-phenotype associations of MAP1B.
Zhou C et al.·Neurol Sci
2025Review
TDP-43 and Cytoskeletal Proteins in ALS.
Oberstadt M et al.·Mol Neurobiol
2018Review
Single-cell and machine learning-based pyroptosis-related gene signature predicts prognosis and immunotherapy response in glioblastoma.
Fang L et al.·Front Immunol
2025
Identification and bioinformatic characterization of a serum miRNA signature for early detection of laryngeal squamous cell carcinoma.
Falco M et al.·J Transl Med
2024
Microtubule-associated protein 1B: Novel paraneoplastic biomarker.
Gadoth A et al.·Ann Neurol
2017
Therapeutic implications of cancer-associated fibroblast heterogeneity: insights from single-cell and multi-omics analysis.
Wang Y et al.·Front Immunol
2025
Functional Consequences of Keratan Sulfate Sulfation in Electrosensory Tissues and in Neuronal Regulation.
Melrose J·Adv Biosyst
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools