MFGE8

Summary

MFGE8 (milk fat globule EGF and factor V/VIII domain containing, HGNC:7036) is a protein-coding gene on chromosome 15q26.1, encoding Lactadherin (Q08431). Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing.

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.

Source: NCBI Gene 4240 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 94 total
• Druggable target: yes
• MANE Select transcript: NM_005928

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7036
Approved symbol	MFGE8
Name	milk fat globule EGF and factor V/VIII domain containing
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	SED1, EDIL1, BA46, OAcGD3S, HsT19888, MFG-E8, hP47
Ensembl gene	ENSG00000140545
Ensembl biotype	protein_coding
OMIM	602281
Entrez	4240

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 20 protein_coding, 7 retained_intron, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000268150, ENST00000268151, ENST00000542878, ENST00000557944, ENST00000558018, ENST00000558029, ENST00000558352, ENST00000558773, ENST00000559143, ENST00000559259, ENST00000559770, ENST00000559997, ENST00000560553, ENST00000560937, ENST00000566497, ENST00000613965, ENST00000617199, ENST00000695566, ENST00000695567, ENST00000695568, ENST00000695569, ENST00000695570, ENST00000695774, ENST00000853374, ENST00000853375, ENST00000853376, ENST00000853377, ENST00000853378, ENST00000853379, ENST00000939054, ENST00000939055, ENST00000939056, ENST00000965377

RefSeq mRNA: 5 — MANE Select: NM_005928 NM_001114614, NM_001310319, NM_001310320, NM_001310321, NM_005928

CCDS: CCDS10347, CCDS45345, CCDS81918, CCDS92057, CCDS92058

Canonical transcript exons

ENST00000268150 — 8 exons

Exon	Start	End
ENSE00002571753	88898683	88899532
ENSE00003488641	88907195	88907376
ENSE00003498009	88906626	88906778
ENSE00003593238	88913247	88913379
ENSE00003610982	88909792	88909923
ENSE00003618632	88905757	88905901
ENSE00003647380	88899656	88899811
ENSE00003687128	88901551	88901735

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.5981 / max 1128.7990, expressed in 1664 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151417	50.9439	1646
151412	1.2380	548
151416	0.7302	458
151415	0.4721	290
151411	0.2139	76

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	99.91	gold quality
ascending aorta	UBERON:0001496	99.88	gold quality
thoracic aorta	UBERON:0001515	99.88	gold quality
right coronary artery	UBERON:0001625	99.84	gold quality
aorta	UBERON:0000947	99.76	gold quality
left coronary artery	UBERON:0001626	99.74	gold quality
popliteal artery	UBERON:0002250	99.72	gold quality
tibial artery	UBERON:0007610	99.72	gold quality
stromal cell of endometrium	CL:0002255	99.68	gold quality
coronary artery	UBERON:0001621	99.68	gold quality
left uterine tube	UBERON:0001303	99.60	gold quality
apex of heart	UBERON:0002098	99.52	gold quality
body of uterus	UBERON:0009853	99.51	gold quality
endocervix	UBERON:0000458	99.41	gold quality
mucosa of stomach	UBERON:0001199	99.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.30	gold quality
lower esophagus	UBERON:0013473	99.28	gold quality
left ovary	UBERON:0002119	99.27	gold quality
ectocervix	UBERON:0012249	99.26	gold quality
right ovary	UBERON:0002118	99.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.23	gold quality
tibial nerve	UBERON:0001323	99.22	gold quality
right lung	UBERON:0002167	99.20	gold quality
right atrium auricular region	UBERON:0006631	99.07	gold quality
omental fat pad	UBERON:0010414	99.05	gold quality
peritoneum	UBERON:0002358	99.02	gold quality
gastrocnemius	UBERON:0001388	98.89	gold quality
heart left ventricle	UBERON:0002084	98.83	gold quality
right uterine tube	UBERON:0001302	98.74	gold quality
skin of leg	UBERON:0001511	98.70	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	2006.45
E-GEOD-137537	yes	1835.34
E-GEOD-134144	yes	1685.74
E-HCAD-11	yes	1521.92
E-MTAB-10018	yes	316.03
E-MTAB-6701	yes	137.41
E-MTAB-10287	yes	78.60
E-MTAB-8410	yes	57.18
E-MTAB-7316	yes	51.32
E-HCAD-1	yes	39.13
E-GEOD-135922	yes	31.28
E-MTAB-6678	yes	27.08
E-HCAD-31	yes	18.82
E-GEOD-93593	yes	16.46
E-HCAD-13	yes	12.51

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IL1B	Repression
SOCS3	Activation
TNF	Repression

Upstream regulators (CollecTRI, top): CEBPB, ESR1, FOXO3, SPI1, TP53, TP63

miRNA regulators (miRDB)

47 targeting MFGE8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-423-5P	98.69	67.48	1522

Literature-anchored findings (GeneRIF, showing 40)

• Truncated fragment of medin, the hexapeptide, NFGSVQ can form typical amyloid fibrils. (PMID:15478463)
• Might prove useful in the treatment of prolonged ischemia. (PMID:16115445)
• Lactadherin) is expressed in normal and atherosclerotic human arteries. (PMID:17420351)
• The trans-activator (TA) isoforms of p63 activate MFGE8 transcription though a p53/p63 motif at -370, which was confirmed by a chromatin immunoprecipitation experiment. (PMID:17637751)
• Identification of the last 18-19 amino acid residues as constituting the amyloid-promoting region of medin. (PMID:17679143)
• aggregated medin induced death of aortic smooth muscle cells in vitro. Cells incubated together with medin increased the production of matrix metalloproteinase-2, a protease that degrades elastin and collagen and subsequently weakens the vessel wall. (PMID:17906662)
• analysis of membrane-interactive loops of Lact-C2 (PMID:18160406)
• Some childhood-onset and adult SLE patients carried a significant level of MFG-E8 in their blood samples. (PMID:18303131)
• Lactadherin promoted phagocytosis of phosphatidylserine-expressing RBCs by macrophages in a concentration-dependent manner. (PMID:18647368)
• findings delineate pleiotropic roles for MFG-E8 in the tumor microenvironment and raise the possibility that systemic MFG-E8 blockade might prove therapeutic for melanoma patients (PMID:18974133)
• SED1 is expressed on the surface of acrosome-intact human sperm and in the anterior caput of the human epididymis, similar to that seen in mouse (PMID:18990388)
• molecular architecture of fibrils formed by the peptide AMed42-49 representing residues 42-49 of the 50 amino acid polypeptide medin (PMID:19196164)
• arterial MFG-E8 significantly increases with aging and is a pivotal relay element within the angiotensin II/MCP-1/VSMC invasion signaling cascade. (PMID:19443842)
• Results suggest that the impairment of phagocytic clearance of apoptotic cells through phosphotidylserine-dependent MFG-E8 system may lead to the development of human systemic lupus erythematosus. (PMID:19502262)
• intronic mutation in the human MFG-E8 gene can lead to the development of SLE. (PMID:20213738)
• overexpression of MFGE8 during bladder tumor development, correlated with expression of genes involved in cell adhesion or migration and in immune responses. (PMID:20956946)
• MFG-E8 is expressed in triple-negative breast cancers as a target gene of the p63 pathway, but may serve a suppressive function in ER(+) and erbB2(+) breast cancers. (PMID:21127199)
• Prolactin has a modulatory role for as a stromal/epithelial paracrine factor controlling MFG-E8. This is the first report on MFG-E8 protein localization to the human endometrial epithelium and its up-regulation during the window of implantation. (PMID:21177637)
• We conclude that MFG-E8-dependent signaling stimulates cell proliferation and the acquisition of mesenchymal properties and contributes to mammary carcinoma development. (PMID:21841820)
• serum lactadherin is correlated with poor blood glucose control and diabetic vascular complications. (PMID:22018779)
• in vitro studies showed that medin amyloid-like fibrils promote the aggregation of protein amyloid A into fibrils (PMID:22070546)
• Decreased colonic MFGE8 expression in patients with ulcerative colitis may be associated with mucosal inflammatory activity and clinical disease activity through basal cell apoptosis and preventing tissue healing in the pathogenesis of ulcerative colitis (PMID:22204000)
• The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” age-related macular Degeneration and their age-matched controls. (PMID:22438901)
• a key role of MFG-E8 release from apoptotic endothelial cells in macrophage reprogramming (PMID:22558449)
• MFG-E8 expression in the endometrial epithelium as well as in chorionic villi suggests its possible role in endometrial reorganization during the receptive phase and in events related to normal pregnancy in mammals (PMID:22770563)
• Milk fat globule-epidermal growth factor 8 has proapoptotic activity, suggesting participation in endometrial remodeling via an epithelial-stromal cell paracrine effect. (PMID:22921913)
• our data argue that MFGE8 is not likely involved in the phagocytic clearance of neuronal debris associated with nigrostriatal pathway injury. (PMID:23194669)
• NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine (PMID:23262193)
• MFG-E8-dependent promotion of apoptotic cell clearance is a novel anti-inflammatory facet of glucocorticoid treatment (PMID:23832117)
• Our results strongly suggested that MFG-E8 is a promising biomarker for the diagnosis, prognosis, and therapy target of opisthorchiasis-associated cholangiocarcinoma (PMID:24122204)
• Lactadherin may decrease inflammation by inhibiting secretory phospholipase A2 activity on pre-apoptotic leukemia cells. (PMID:24194865)
• TNF-alpha up-regulates endometrial epithelial cell migration and MFG-E8 production. (PMID:24262600)
• Blockage of MFG-E8 in endometrial tumor cells diminishes trophoblaast cell attachment. (PMID:24424369)
• MFG-E8 could be used as a biomarker for diagnosis and monitoring of disease activity in certain systemic lupus erythematosus patients (PMID:24554711)
• MFG-E8 had a negative association with hs-CRP and a positive association with LDL-c. The serum level of MFG-E8 was negatively associated with the severity of coronary artery stenosis and the risk of clinical events. (PMID:24561551)
• medin adopts a predominantly beta-sheet conformation with some unstructured elements. (PMID:24602872)
• MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis. (PMID:24838098)
• Exogenously added MFG-E8 inhibits receptor activator NF-kappaB ligand-induced osteoclastogenesis of human osteoclast precursors. (PMID:24958900)
• promotes tumor progression in oral squamous cell carcinoma (PMID:25264705)
• Studied the therapeutic effect of rhMFG-E8 in mouse models of IBD. Treatment with rhMFG-E8 significantly attenuated colitis in both models in a dose-dependent way. (PMID:25751740)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfge8a	ENSDARG00000015349
danio_rerio	mfge8b	ENSDARG00000045803
mus_musculus	Mfge8	ENSMUSG00000030605
rattus_norvegicus	Mfge8	ENSRNOG00000017510

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Lactadherin — Q08431 (reviewed: Q08431)

Alternative names: Breast epithelial antigen BA46, HMFG, MFGM, Milk fat globule-EGF factor 8, SED1

All UniProt accessions (8): A0A8Q3SI86, A0A8Q3SIU8, A0A8Q3SIX6, A0A8Q3SIZ9, A0A8Q3WKS4, Q08431, H0YKB5, H0YKS8

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization. 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. Main constituent of aortic medial amyloid.

Subcellular location. Membrane. Secreted. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane.

Tissue specificity. Mammary epithelial cell surfaces and aortic media. Overexpressed in several carcinomas.

Post-translational modifications. Medin has a ragged N-terminus with minor species starting at Pro-264 and Gly-273.

Domain organisation. The F5/8 type C 2 domain mediates high-affinity binding to phosphatidylserine-containing membranes.

Miscellaneous. It is unsure whether Met-1 or an upstream Met is the initiator as the upstream Met corresponds to polymorphism rs1879326.

Isoforms (4)

UniProt ID	Names	Canonical?
Q08431-1	1	yes
Q08431-2	2
Q08431-3	3
Q08431-4	4

RefSeq proteins (5): NP_001108086, NP_001297248, NP_001297249, NP_001297250, NP_005919* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR000742	EGF	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR050633	Neuropilin_MCO_CoagFactor	Family

Pfam: PF00008, PF00754

UniProt features (27 total): disulfide bond 6, glycosylation site 5, chain 3, splice variant 3, domain 3, sequence variant 2, sequence conflict 2, signal peptide 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9U02	ELECTRON MICROSCOPY	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08431-F1	87.86	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 42

Disulfide bonds (6): 27–38, 32–55, 57–66, 70–225, 212–216, 230–387

Glycosylation sites (5): 238, 325, 329, 350, 228

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-977225	Amyloid fiber formation
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 252 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOCC_CELL_SURFACE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_APOPTOTIC_CELL_CLEARANCE, MEF2_02, GOBP_VESICLE_MEDIATED_TRANSPORT, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GOBP_BLOOD_VESSEL_MORPHOGENESIS, NADLER_OBESITY_UP

GO Biological Process (4): angiogenesis (GO:0001525), cell adhesion (GO:0007155), single fertilization (GO:0007338), apoptotic cell clearance (GO:0043277)

GO Molecular Function (3): phosphatidylserine binding (GO:0001786), integrin binding (GO:0005178), extracellular matrix structural constituent (GO:0005201)

GO Cellular Component (11): acrosomal membrane (GO:0002080), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), external side of plasma membrane (GO:0009897), membrane (GO:0016020), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), extracellular vesicle (GO:1903561), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of proteins	3
Post-translational protein modification	1
Developmental Lineages of the Mammary Gland	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
plasma membrane	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cellular process	1
fertilization	1
phagocytosis	1
phospholipid binding	1
anion binding	1
modified amino acid binding	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
structural molecule activity	1
extracellular matrix	1
acrosomal vesicle	1
secretory granule membrane	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cell surface	1
side of membrane	1
external encapsulating structure	1
extracellular vesicle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1
vacuole	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

2148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFGE8	ITGAV	P06756	976
MFGE8	GAS6	Q14393	927
MFGE8	MERTK	Q12866	815
MFGE8	EGF	P01133	809
MFGE8	ICAM1	P05362	797
MFGE8	BTNL3	Q6UXE8	783
MFGE8	BTN2A2	Q8WVV5	782
MFGE8	ERMAP	Q96PL5	782
MFGE8	BTNL8	Q6UX41	778
MFGE8	BTN1A1	Q13410	777
MFGE8	BTN3A3	O00478	777
MFGE8	ITGB5	P18084	777
MFGE8	BTN2A1	P78408	777
MFGE8	BTNL9	Q6UXG8	772
MFGE8	BTN3A2	P78410	771

IntAct

69 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
	PLOD2	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ADAM10	TSPAN9	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
MYC	PDZD2	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SLURP1	MANBA	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
MFGE8	ITGB5	psi-mi:“MI:0914”(association)	0.350
VEGFD	RPSA2	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ITM2C		psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): MFGE8 (Affinity Capture-MS), MFGE8 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), ITGB5 (Affinity Capture-MS), ITGB5 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), MFGE8 (Affinity Capture-MS), MFGE8 (Co-fractionation), MFGE8 (Co-fractionation), MFGE8 (Affinity Capture-MS), MFGE8 (Affinity Capture-MS), MFGE8 (Affinity Capture-MS), MFGE8 (Proximity Label-MS), MFGE8 (Proximity Label-MS), MFGE8 (Proximity Label-MS)

ESM2 similar proteins: D3ZTD8, O15537, O35276, O35375, O35474, O42163, O43405, O43854, O60462, O75882, P02469, P07224, P07225, P07942, P18614, P21956, P48740, P55245, P56199, P70490, P79385, P98064, P98118, Q01279, Q01635, Q08431, Q13591, Q28520, Q2VWQ2, Q3V3R4, Q5E9T6, Q5EA64, Q5R7K9, Q62217, Q62507, Q63604, Q6IS24, Q7TT15, Q8CHN8, Q8R4G0

Diamond homologs: A2RUV9, A5A6K7, O14786, O17754, O18806, O35276, O35375, O35474, O43854, O54858, O54991, O60462, O75976, O88783, O89001, P00451, P02886, P02887, P02888, P04836, P12259, P12263, P14384, P15087, P15169, P16870, P21956, P28824, P29068, P37892, P39041, P42787, P70490, P78357, P79385, P79795, P83852, P97333, P97846, P98092

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
MFGE8	“up-regulates quantity by expression”	SOCS3	“transcriptional regulation”
MFGE8	“up-regulates activity”	STAT3
MFGE8	“up-regulates quantity by expression”	GRK2
MFGE8	“down-regulates quantity by repression”	IL1B	“transcriptional regulation”
MFGE8	“down-regulates quantity by repression”	TNF	“transcriptional regulation”
MFGE8	“up-regulates activity”	“Av/b3 integrin”	binding
MFGE8	“up-regulates activity”	“Av/b5 integrin”	binding
MFGE8	down-regulates	Fibrosis
MFGE8	“down-regulates activity”	p38
MFGE8	“down-regulates activity”	NfKb-p65/p50

Disease & clinical

Clinical variants and AI predictions

ClinVar

94 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	9
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1989 predictions. Top by Δscore:

Variant	Effect	Δscore
15:88899529:AGAT:A	acceptor_gain	1.0000
15:88899532:TCTAG:T	acceptor_loss	1.0000
15:88899533:C:CC	acceptor_gain	1.0000
15:88899533:CTA:C	acceptor_loss	1.0000
15:88899652:CCA:C	donor_loss	1.0000
15:88899654:A:AC	donor_gain	1.0000
15:88899655:C:CC	donor_gain	1.0000
15:88899655:C:G	donor_loss	1.0000
15:88899655:CCTTA:C	donor_gain	1.0000
15:88899659:A:AC	donor_gain	1.0000
15:88899660:C:CC	donor_gain	1.0000
15:88899660:CTG:C	donor_gain	1.0000
15:88899689:AGT:A	donor_gain	1.0000
15:88906621:CCTA:C	donor_loss	1.0000
15:88906622:CTAC:C	donor_loss	1.0000
15:88906623:TA:T	donor_loss	1.0000
15:88906624:A:T	donor_loss	1.0000
15:88906777:ACC:A	acceptor_loss	1.0000
15:88906780:T:A	acceptor_loss	1.0000
15:88907189:GCATA:G	donor_loss	1.0000
15:88907190:CATAC:C	donor_loss	1.0000
15:88907191:ATACC:A	donor_loss	1.0000
15:88907192:TA:T	donor_loss	1.0000
15:88907373:CATT:C	acceptor_gain	1.0000
15:88907375:TT:T	acceptor_gain	1.0000
15:88907377:C:CA	acceptor_loss	1.0000
15:88907377:C:CC	acceptor_gain	1.0000
15:88909786:A:AC	donor_gain	1.0000
15:88909787:C:CC	donor_gain	1.0000
15:88909787:CTCA:C	donor_gain	1.0000

AlphaMissense

2548 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:88899456:C:G	R368P	0.999
15:88907231:C:A	W117C	0.999
15:88907231:C:G	W117C	0.999
15:88899417:C:G	R381P	0.998
15:88899768:T:G	Q305P	0.998
15:88901587:C:A	W278C	0.998
15:88901587:C:G	W278C	0.998
15:88905786:C:G	R219P	0.998
15:88906735:T:G	Q144P	0.998
15:88907233:A:G	W117R	0.998
15:88907233:A:T	W117R	0.998
15:88909800:C:G	C66S	0.998
15:88909801:A:T	C66S	0.998
15:88909833:C:G	C55S	0.998
15:88909834:A:T	C55S	0.998
15:88909884:C:G	C38S	0.998
15:88909885:A:T	C38S	0.998
15:88909902:C:G	C32S	0.998
15:88909903:A:T	C32S	0.998
15:88901589:A:G	W278R	0.997
15:88901589:A:T	W278R	0.997
15:88907196:T:G	Q129P	0.997
15:88909799:A:C	C66W	0.997
15:88909832:G:C	C55W	0.997
15:88899692:C:A	W330C	0.996
15:88899692:C:G	W330C	0.996
15:88899718:C:G	A322P	0.996
15:88899737:A:C	F315L	0.996
15:88899737:A:T	F315L	0.996
15:88899739:A:G	F315L	0.996

dbSNP variants (sampled 300 via entrez): RS1000071544 (15:88909533 G>A), RS1000123394 (15:88913632 G>C), RS1000176744 (15:88902036 C>T), RS1000233337 (15:88901769 G>A,C), RS1000237487 (15:88913416 G>A,T), RS1000730037 (15:88912678 A>G), RS1001454496 (15:88902004 G>C), RS1001740595 (15:88907827 C>G), RS1001795449 (15:88912568 T>G), RS1001796647 (15:88907917 G>C), RS1001845449 (15:88900826 T>C), RS1001904039 (15:88913304 G>A,C), RS1002356261 (15:88913049 GC>G), RS1002475719 (15:88906644 A>T), RS1002633644 (15:88915098 T>G)

Disease associations

OMIM: gene MIM:602281 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST003116_4	Coronary artery disease	4.000000e-08
GCST004750_10	Squamous cell lung carcinoma	9.000000e-06
GCST004787_61	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	1.000000e-07
GCST006585_949	Blood protein levels	4.000000e-26
GCST007096_9	Pulse pressure	2.000000e-08
GCST008839_83	Height	2.000000e-12
GCST010479_38	Coronary artery disease	4.000000e-10
GCST010866_64	Coronary artery disease	2.000000e-26
GCST010867_13	Coronary artery disease	9.000000e-18
GCST012305_9	Major depressive disorder x sex interaction	5.000000e-06
GCST90011900_118	Serum alkaline phosphatase levels	7.000000e-16
GCST90013406_57	Liver enzyme levels (alkaline phosphatase)	7.000000e-20
GCST90020028_1461	Hip circumference adjusted for BMI	2.000000e-10
GCST90020028_1462	Hip circumference adjusted for BMI	8.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0008343	sex interaction measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713343 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Doxorubicin	affects expression, increases expression	3
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
potassium perchlorate	increases expression	1
trichostatin A	decreases expression	1
o,p’-DDT	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
tamibarotene	increases expression	1
delta-aminolevulinic acid methyl ester	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
procyanidin B2	decreases expression, increases activity, increases expression, affects response to substance, affects localization (+1 more)	1
licochalcone B	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1
Dasatinib	increases expression	1
Resveratrol	affects localization, decreases reaction, decreases expression, increases activity, increases expression (+1 more)	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.