MT4

protein-coding

metallothionein 4, the group of Metallothioneins

Gene summary

Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including cellular response to zinc ion; detoxification of copper ion; and intracellular zinc ion homeostasis. Predicted to act upstream of or within intracellular monoatomic cation homeostasis. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032935.3

Inheritance

—

ClinVar variants

U:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.43

Max pathogenic AF

—

Genomic locus

chr16:56,565,073-56,568,957

External References & Databases

Ensembl (ENSG00000102891)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MT4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032935.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			13 clinvar			13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	14	0	0	14

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032935.3	RefSeq	NP_116324.2	3	MANE Select
ENST00000219162.4	Ensembl	ENSP00000219162.3	3	MANE Select
ENST00001136995.1	Ensembl	ENSP00000801632.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Copper homeostasis
Zinc homeostasis
Response to metal ions
Cellular responses to external stimuli
Metallothioneins bind metals

Biological Process

cellular zinc ion homeostasis
biological_process
detoxification of copper ion
cellular response to cadmium ion
cellular response to copper ion

Molecular Function

metal ion binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219162
Coding exons: 3
Length: 3909
Individuals with no LoFs: 125123
Homozygous LoFs: 0
Heterozygous LoFs: 152
Defined: 125275
p: 0.000607

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.360	40	34.1	1.17	0.00000169	405
Missense (PolyPhen)		7	5.7659	1.214		59
Synonymous	-0.383	12	10.4	1.15	5.30e-7	92
Loss of Function	-0.746	5	3.49	1.43	1.46e-7	49

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.0038	0.0036	notable
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Seems to bind zinc and copper. Could play a special role in regulating zinc metabolism during the differentiation of stratified epithelia.;

Recessive Scores

pRec: 0.253

Intolerance Scores

RVIS EVS: 0.66
RVIS percentile EVS: 84.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0211

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium