MELTF

Chr 3

melanotransferrin

Also known as: CD228, MAP97, MFI2, MTF1, MTf

This protein is a cell-surface glycoprotein that binds and transports iron into cells, with structural similarity to the transferrin family of iron-binding proteins. Mutations cause melanotransferrin deficiency, which is inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants, suggesting complete loss may be tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
88
P/LP submissions
P/LP missense
1.13
LOEUF
DN
Mechanism· predicted
Clinical SummaryMELTF
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
87 unique Pathogenic / Likely Pathogenic· 30 VUS of 155 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 0.94
OE 0.83 (0.611.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.01Z-score
OE missense 1.00 (0.931.08)
469 obs / 468.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.83 (0.611.13)
00.351.4
Missense OE1.00 (0.931.08)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 28 / 33.9Missense obs/exp: 469 / 468.1Syn Z: -0.80
DN
0.6455th %ile
GOF
0.6247th %ile
LOF
0.2874th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

155 submitted variants in ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic3
VUS30
Benign1
Conflicting1
84
Pathogenic
3
Likely Pathogenic
30
VUS
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
84
Likely Pathogenic
3
VUS
30
Likely Benign
0
Benign
1
Conflicting
1
Total119

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MELTF · protein map & ClinVar variants

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

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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