MTF1

Chr 1

metal regulatory transcription factor 1

Also known as: MTF-1, ZRF

NCBI Gene: 4520 ENSG00000188786 UniProt: Q01538 OMIM: 600172

This gene encodes a transcription factor that regulates metallothionein expression and metal homeostasis in response to heavy metals, and also binds to promoters of genes encoding central nervous system proteolipid proteins. The gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.32), suggesting mutations would likely cause severe developmental phenotypes. However, no specific disease associations or inheritance patterns have been established for this gene based on the provided information.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.32

Clinical Summary— MTF1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

61 VUS of 85 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.969

Z-score 4.50

OE 0.15 (0.08–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.54Z-score

OE missense 0.65 (0.59–0.72)

272 obs / 418.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.32)

0≤0.351.4

Missense OE?0.65 (0.59–0.72)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 5 / 32.8Missense obs/exp: 272 / 418.2Syn Z: 0.48

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedMTF1-related intellectual disabilityLOFAD

This gene — mechanism propensity

0.4190th %ile

GOF

0.2994th %ile

LOF

0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.32

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

VUS61

Likely Benign7

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	60	0	61
Likely Benign	0	3	4	7
Benign	0	2	1	3
Total	1	65	5	71

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

5 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap MTF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →