MTA2

Chr 11

metastasis associated 1 family member 2

Also known as: MTA1L1, PID

NCBI Gene: 9219 ENSG00000149480 UniProt: O94776

This gene encodes a component of the NuRD nucleosome remodeling deacetylase complex that functions as a transcriptional coregulator and participates in chromatin remodeling. Mutations cause neurodevelopmental disorder with severe intellectual disability, absent language, and distinctive facial features, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, reflecting its critical role in normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that has been identified as a component of NuRD, a nucleosome remodeling deacetylase complex identified in the nucleus of human cells. It shows a very broad expression pattern and is strongly expressed in many tissues. It may represent one member of a small gene family that encode different but related proteins involved either directly or indirectly in transcriptional regulation. Their indirect effects on transcriptional regulation may include chromatin remodeling. It is closely related to another member of this family, a protein that has been correlated with the metastatic potential of certain carcinomas. These two proteins are so closely related that they share the same types of domains. These domains include two DNA binding domains, a dimerization domain, and a domain commonly found in proteins that methylate DNA. One of the proteins known to be a target protein for this gene product is p53. Deacetylation of p53 is correlated with a loss of growth inhibition in transformed cells supporting a connection between these gene family members and metastasis. [provided by RefSeq, May 2011]

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

0.36

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.36LOEUF

pLI 0.745

Z-score 4.66

OE 0.20 (0.12–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.13Z-score

OE missense 0.56 (0.50–0.63)

224 obs / 399.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.20 (0.12–0.36)

0≤0.351.4

Missense OE?0.56 (0.50–0.63)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 8 / 39.7Missense obs/exp: 224 / 399.9Syn Z: -0.85

Background carrier burden — how many people carry a rare variant somewhere in MTA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

590 rare PASS variants

Rare truncating (LoF)

1 in 4,500

50 rare PASS variants

Rare synonymous (reference)

1 in 170

330 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTA2. 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 200	1 in 10,000
South Asian	~43k	1 in 140	1 in 8,600
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 10,000
European (Finnish)	~27k	1 in 950	1 in 3,000
Admixed American	~22k	1 in 190	1 in 1,700
African / African American	~21k	1 in 150	1 in 2,900
East Asian	~20k	1 in 160	1 in 4,000
Ashkenazi Jewish	~13k	1 in 580	1 in 1,400
Middle Eastern	~2,884	1 in 160	≈ 1 in 2,900

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): All 18 coding exons well covered in gnomAD exomes and genomes.? see exons ↓