MFGE8

protein-coding

milk fat globule EGF and factor V/VIII domain containing

Gene summary

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]

Previous symbols:

SPAG10

MANE transcript

NM_005928.4

Inheritance

—

ClinVar variants

U:72B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr15:88,898,683-88,913,468

External References & Databases

Ensembl (ENSG00000140545)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MFGE8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005928.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	4 clinvar	7
missense			68 clinvar	6 clinvar	2 clinvar	76
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	72	9	6	87

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005928.4	RefSeq	NP_005919.2	8	MANE Select
ENST00000268150.13	Ensembl	ENSP00000268150.8	8	MANE Select
NM_001114614.3	RefSeq	NP_001108086.1	7	Standard
NM_001310319.2	RefSeq	NP_001297248.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Extracellular vesicle-mediated signaling in recipient cells
Glucocorticoid Receptor Pathway
Nuclear Receptors Meta-Pathway
Ebola Virus Pathway on Host
Ebola Virus Pathway on Host

Biological Process

angiogenesis
phagocytosis, recognition
phagocytosis, engulfment
cell adhesion
single fertilization

Molecular Function

phosphatidylserine binding
integrin binding
extracellular matrix structural constituent
phosphatidylethanolamine binding

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum lumen
external side of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000268150
Coding exons: 8
Length: 14727
Individuals with no LoFs: 125543
Homozygous LoFs: 1
Heterozygous LoFs: 204
Defined: 125748
p: 0.000815

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.365	237	222	1.07	0.0000150	2530
Missense (PolyPhen)		107	96.761	1.1058		1103
Synonymous	-0.919	107	95.6	1.12	0.00000691	756
Loss of Function	1.90	10	18.9	0.529	9.19e-7	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00023	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.0059	0.0059	notable
European (Non-Finnish)	0.00029	0.00029	rare
South Asian	0.00082	0.00082	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization (By similarity). Contributes to phagocytic removal of apoptotic cells in many tissues. Specific ligand for the alpha-v/beta-3 and alpha-v/beta-5 receptors. Also binds to phosphatidylserine-enriched cell surfaces in a receptor-independent manner. Zona pellucida-binding protein which may play a role in gamete interaction. {ECO:0000250, ECO:0000269|PubMed:19204935}.;

Intolerance Scores

LoFtool: 0.0884
RVIS EVS: -0.53
RVIS percentile EVS: 20.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.657

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium