MFGE8

Chr 15

milk fat globule EGF and factor V/VIII domain containing

Also known as: BA46, EDIL1, HMFG, HsT19888, MFG-E8, MFGM, OAcGD3S, SED1

This gene encodes a preproprotein that is proteolytically processed to form multiple protein products. The major encoded protein product, lactadherin, is a membrane glycoprotein that promotes phagocytosis of apoptotic cells. This protein has also been implicated in wound healing, autoimmune disease, and cancer. Lactadherin can be further processed to form a smaller cleavage product, medin, which comprises the major protein component of aortic medial amyloid (AMA). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.90
Clinical SummaryMFGE8
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?
0.90LOEUF
pLI 0.000
Z-score 1.90
OE 0.53 (0.330.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.36Z-score
OE missense 1.07 (0.961.19)
237 obs / 221.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.53 (0.330.90)
00.351.4
Missense OE?1.07 (0.961.19)
00.61.4
Synonymous OE?1.12
01.21.6
LoF obs/exp: 10 / 18.9Missense obs/exp: 237 / 221.7Syn Z: -0.92

This gene — mechanism propensity

DN
0.7327th %ile
GOF
0.7125th %ile
LOF
0.2775th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MFGE8 · 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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