MAP1B

Chr 5AD

microtubule associated protein 1B

Also known as: DFNA83, FUTSCH, MAP5, PPP1R102, PVNH9

NCBI Gene: 4131 ENSG00000131711 UniProt: P46821 OMIM: 157129

MAP1B encodes a microtubule-associated protein that facilitates tubulin modification and is required for proper microtubule dynamics during neuronal differentiation and neurite extension. Mutations cause autosomal dominant deafness and periventricular nodular heterotopia, a brain malformation affecting neuronal migration. This gene is extremely intolerant to loss-of-function variants, reflecting its critical role in nervous system development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, 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 product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1B heavy chain and LC1 light chain. Gene knockout studies of the mouse microtubule-associated protein 1B gene suggested an important role in development and function of the nervous system. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.132 OMIM phenotypes

Clinical Summary— MAP1B

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Gene-Disease Validity (ClinGen)

periventricular nodular heterotopia · ADStrong

Strong evidence — appropriate for clinical testing

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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.

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ClinVar Variants

40 unique Pathogenic / Likely Pathogenic· 418 VUS of 648 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MAP1B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.06 (0.03–0.13)

0≤0.351.4

Missense OE?0.80 (0.76–0.85)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 5 / 79.1Missense obs/exp: 1051 / 1306.4Syn Z: -0.05

This gene — mechanism propensity

0.2598th %ile

GOF

0.3392th %ile

LOF

0.80top 5%

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

LOFprediction above median · 95% of P/LP variants are LoF · LOEUF 0.13

DN1 literature citation

Literature Evidence

DNBecause the gene targeting event in these mice produced a gene encoding a 571-amino acid truncated product of MAP1B, it seems likely that the phenotypes seen arise from the truncated MAP1B product acting in a dominant-negative fashion, rather than a loss of MAP1B function.1

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.PMID 9199175 ↗

ClinVar Variant Classifications

648 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic21

VUS418

Likely Benign152

Benign21

Conflicting4

Pathogenic

Likely Pathogenic

418

VUS

152

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	1	0	0	19
Likely Pathogenic	20	1	0	0	21
VUS	4	412	2	0	418
Likely Benign	0	69	3	80	152
Benign	0	9	0	12	21
Conflicting	—				4
Total	42	492	5	92	635

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap MAP1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →