MTF1

protein-coding

metal regulatory transcription factor 1

Gene summary

This gene encodes a transcription factor that induces expression of metallothioneins and other genes involved in metal homeostasis in response to heavy metals such as cadmium, zinc, copper, and silver. The protein is a nucleocytoplasmic shuttling protein that accumulates in the nucleus upon heavy metal exposure and binds to promoters containing a metal-responsive element (MRE). [provided by RefSeq, Jul 2008]

MANE transcript

NM_005955.3

Inheritance

ClinVar variants

U:68B:13

Top phenotype

Autism spectrum disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr1:37,809,574-37,859,592

External References & Databases

Ensembl (ENSG00000188786)

Transcript & Mutation Effects

hg38 • Region Span ~50.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001071

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTF1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 68

not providedTotal: 8

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005955.3. 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			4 clinvar	7 clinvar	1 clinvar	12
missense			63 clinvar	3 clinvar	2 clinvar	68
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	68	10	3	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005955.3	RefSeq	NP_005946.2	10	MANE Select
ENST00000373036.5	Ensembl	ENSP00000362127.3	10	MANE Select
ENST00000880495.1	Ensembl	ENSP00000550554.1	10	Standard
ENST00000880495.2	Ensembl	ENSP00000550554.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Copper homeostasis
Zinc homeostasis
MTF1 activates gene expression
Response to metal ions
Cellular responses to external stimuli

Biological Process

regulation of transcription by RNA polymerase II
response to oxidative stress
central nervous system development
response to metal ion
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
proximal promoter sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373036
Coding exons: 10
Length: 50054
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125748
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.54	272	418	0.650	0.0000219	4903
Missense (PolyPhen)		61	149	0.40939		1748
Synonymous	0.481	159	167	0.953	0.00000951	1547
Loss of Function	4.50	5	32.8	0.152	0.00000190	350

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates the metallothionein I promoter. Binds to the metal responsive element (MRE). {ECO:0000269|PubMed:8065932}.;

Recessive Scores

pRec: 0.0966

Intolerance Scores

LoFtool: 0.211
RVIS EVS: 0.0000761
RVIS percentile EVS: 53.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.578

Gene Damage Prediction

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