MT1A

Chr 16

metallothionein 1A

Also known as: MT-1A, MT-IA, MT1, MT1S, MTC

NCBI Gene: 4489 ENSG00000205362 UniProt: P04731 OMIM: 156350

Metallothionein 1A encodes a small, cysteine-rich protein that binds heavy metals and functions as an antioxidant to protect against oxidative stress and heavy metal toxicity. The gene is not highly constrained against loss-of-function variants (pLI = 0.004, LOEUF = 1.9), and no Mendelian diseases have been definitively associated with MT1A mutations in humans. Mouse studies suggest metallothioneins may play roles in metal homeostasis, immune function, and metabolic regulation.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions. The conserved cysteine residues co-ordinate metal ions using mercaptide linkages. These proteins act as anti-oxidants, protect against hydroxyl free radicals, are important in homeostatic control of metal in the cell, and play a role in detoxification of heavy metals. Disruption of two metallothionein genes in mouse resulted in defects in protection against heavy metals, oxidative stress, immune reactions, carcinogens, and displayed obesity. [provided by RefSeq, Sep 2017]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.91

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.91LOEUF

pLI 0.004

Z-score -0.34

OE 1.23 (0.50–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.08Z-score

OE missense 0.96 (0.72–1.29)

31 obs / 32.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.23 (0.50–1.91)

0≤0.351.4

Missense OE?0.96 (0.72–1.29)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 3 / 2.4Missense obs/exp: 31 / 32.3Syn Z: -0.08

Background carrier burden — how many people carry a rare variant somewhere in MT1A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 2,700

73 rare PASS variants

Rare truncating (LoF)

1 in 11,000

18 rare PASS variants

Rare synonymous (reference)

1 in 2,800

24 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MT1A; this gene does not show strong loss-of-function constraint by this measure. 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 2,600	1 in 7,900
South Asian	~43k	1 in 3,300	1 in 7,200
Remaining (unassigned)	~30k	1 in 2,300	1 in 6,000
European (Finnish)	~27k	1 in 5,300	none seen
Admixed American	~22k	1 in 2,800	≈ 1 in 22,000
African / African American	~21k	1 in 770	≈ 1 in 5,600
East Asian	~20k	1 in 2,500	≈ 1 in 20,000
Ashkenazi Jewish	~13k	none seen	≈ 1 in 6,500
Middle Eastern	~2,884	≈ 1 in 1,400	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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓