MAP6

Chr 11

microtubule associated protein 6

Also known as: MAP6-N, MTAP6, N-STOP, STOP

NCBI Gene: 4135 ENSG00000171533 UniProt: Q96JE9

The protein stabilizes microtubules and regulates axonal transport and dendrite morphogenesis in neurons. Mutations cause autosomal recessive intellectual disability with macrocephaly, seizures, and spasticity. The gene shows moderate constraint against loss-of-function variants, and affected individuals typically present with developmental delays and neurological symptoms in early childhood.

ResearchSummary from RefSeq, UniProt

This gene encodes a microtubule-associated protein. The encoded protein is a calmodulin-binding and calmodulin-regulated protein that is involved in microtubule stabilization. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.57

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.395

Z-score 2.67

OE 0.22 (0.10–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.39Z-score

OE missense 0.79 (0.72–0.88)

280 obs / 353.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.10–0.57)

0≤0.351.4

Missense OE?0.79 (0.72–0.88)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 3 / 13.6Missense obs/exp: 280 / 353.3Syn Z: 1.00

Background carrier burden — how many people carry a rare variant somewhere in MAP6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 61

1,049 rare PASS variants

Rare truncating (LoF)

1 in 1,800

101 rare PASS variants

Rare synonymous (reference)

1 in 75

465 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAP6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 86	1 in 1,800
South Asian	~43k	1 in 52	1 in 940
Remaining (unassigned)	~30k	1 in 53	1 in 2,700
European (Finnish)	~27k	1 in 130	≈ 1 in 6,100
Admixed American	~22k	1 in 47	1 in 570
African / African American	~21k	1 in 65	≈ 1 in 5,600
East Asian	~20k	1 in 71	1 in 840
Ashkenazi Jewish	~13k	1 in 220	1 in 1,900
Middle Eastern	~2,884	1 in 63	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 4.? see exons ↓