MELTF

Chr 3

melanotransferrin

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

NCBI Gene: 4241 ENSG00000163975 UniProt: P08582 OMIM: 155750

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a cell-surface glycoprotein found on melanoma cells. The protein shares sequence similarity and iron-binding properties with members of the transferrin superfamily. The importance of the iron binding function has not yet been identified. This gene resides in the same region of chromosome 3 as members of the transferrin superfamily. Alternative splicing results in two transcript variants. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.13

Clinical Summary— MELTF

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 VUS of 48 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 0.94

OE 0.83 (0.61–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.93–1.08)

469 obs / 468.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.61–1.13)

0≤0.351.4

Missense OE?1.00 (0.93–1.08)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 28 / 33.9Missense obs/exp: 469 / 468.1Syn Z: -0.80

This gene — mechanism propensity

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

48 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	13	13
Likely Benign	0	0
Benign	1	1
Total	14	14

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 52) ClinVar copy-number / structural variants overlap MELTF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →