MFSD1

Chr 3

major facilitator superfamily domain containing 1

Also known as: Minerva, SLC72A1, SMAP4

NCBI Gene: 64747 ENSG00000118855 UniProt: Q9H3U5 OMIM: 619976

Enables dipeptide uniporter activity. Involved in dipeptide transmembrane transport from lysosomal lumen to cytosol. Is active in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.25

Clinical Summary— MFSD1

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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

78 VUS of 118 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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?

1.25LOEUF

pLI 0.000

Z-score 0.48

OE 0.91 (0.67–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.00 (0.91–1.11)

280 obs / 278.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.91 (0.67–1.25)

0≤0.351.4

Missense OE?1.00 (0.91–1.11)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 27 / 29.8Missense obs/exp: 280 / 278.9Syn Z: -0.92

This gene — mechanism propensity

0.6452th %ile

GOF

0.6345th %ile

LOF

0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

118 submitted variants in ClinVar

ClinVar

Classification Summary

VUS78

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	69	9	0	78
Likely Benign	2	1	1	4
Benign	0	0	0	0
Total	71	10	1	82

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap MFSD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →