MFSD12

Chr 19

major facilitator superfamily domain containing 12

Also known as: C19orf28, PP3501, SLC59B1

The protein is a cysteine transporter that imports cysteine into melanosomes and lysosomes, regulating skin pigmentation and cellular redox homeostasis. Mutations cause oculocutaneous albinism type 9, an autosomal recessive disorder affecting pigmentation in the eyes, skin, and hair. The gene shows tolerance to loss-of-function variants (LOEUF 1.42), consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.42
Clinical SummaryMFSD12
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.42LOEUF
pLI 0.000
Z-score -0.11
OE 1.02 (0.751.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.74Z-score
OE missense 1.43 (1.321.54)
459 obs / 321.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.02 (0.751.42)
00.351.4
Missense OE1.43 (1.321.54)
00.61.4
Synonymous OE1.40
01.21.6
LoF obs/exp: 26 / 25.4Missense obs/exp: 459 / 321.0Syn Z: -3.91
DN
0.6646th %ile
GOF
0.6833th %ile
LOF
0.3065th %ile

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

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MFSD12 · 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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