MAP2

Chr 2

microtubule associated protein 2

Also known as: MAP-2, MAP2A, MAP2B, MAP2C

NCBI Gene: 4133 ENSG00000078018 UniProt: P11137

This gene encodes microtubule-associated protein 2 (MAP2), a neuron-specific cytoskeletal protein that stabilizes microtubules and determines dendritic shape during neuronal development. Mutations cause autosomal dominant neurodevelopmental disorders affecting the brain. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The products of similar genes in rat and mouse are neuron-specific cytoskeletal proteins that are enriched in dentrites, implicating a role in determining and stabilizing dentritic shape during neuron development. A number of alternatively spliced variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2010]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.10

Clinical Summary— MAP2

⚡

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

203 VUS of 260 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 6.95

OE 0.03 (0.01–0.10)

Highly constrained

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

Missense Constraint?

0.88Z-score

OE missense 0.92 (0.87–0.97)

885 obs / 962.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.10)

0≤0.351.4

Missense OE?0.92 (0.87–0.97)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 2 / 60.1Missense obs/exp: 885 / 962.2Syn Z: -0.58

This gene — mechanism propensity

0.3196th %ile

GOF

0.3690th %ile

LOF

0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.10

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

ClinVar Variant Classifications

260 submitted variants in ClinVar

ClinVar

Classification Summary

VUS203

Likely Benign26

Benign12

203

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	202	0	0	203
Likely Benign	0	13	0	13	26
Benign	0	5	1	6	12
Total	1	220	1	19	241

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap MAP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →