MTF1

Chr 1

metal regulatory transcription factor 1

Also known as: MTF-1, ZRF

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.32
Clinical SummaryMTF1
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.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 64 VUS of 94 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.969
Z-score 4.50
OE 0.15 (0.080.32)
Highly constrained

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

Missense Constraint
2.54Z-score
OE missense 0.65 (0.590.72)
272 obs / 418.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.080.32)
00.351.4
Missense OE0.65 (0.590.72)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 5 / 32.8Missense obs/exp: 272 / 418.2Syn Z: 0.48
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMTF1-related intellectual disabilityLOFAD
DN
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

94 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS64
Likely Benign8
Benign3
4
Pathogenic
1
Likely Pathogenic
64
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
1
60
3
0
64
Likely Benign
0
3
1
4
8
Benign
0
2
0
1
3
Total1659580

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

View in ClinVar →

Protein Context — Lollipop Plot

MTF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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