MEGF6

Summary

MEGF6 (multiple EGF like domains 6, HGNC:3232) is a protein-coding gene on chromosome 1p36.32, encoding Multiple epidermal growth factor-like domains protein 6 (O75095).

Predicted to enable calcium ion binding activity and scavenger receptor activity. Predicted to be involved in vesicle-mediated transport. Predicted to be located in extracellular region.

Source: NCBI Gene 1953 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 391 total — 2 pathogenic
• MANE Select transcript: NM_001409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3232
Approved symbol	MEGF6
Name	multiple EGF like domains 6
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162591
Ensembl biotype	protein_coding
OMIM	604266
Entrez	1953

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 20 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000294599, ENST00000356575, ENST00000461795, ENST00000475790, ENST00000485002, ENST00000491842, ENST00000494257, ENST00000697102, ENST00000909778, ENST00000909779, ENST00000909780, ENST00000920604, ENST00000920605, ENST00000920606, ENST00000920607, ENST00000920608, ENST00000920609, ENST00000920610, ENST00000954838, ENST00000954839, ENST00000954840, ENST00000954841, ENST00000954842, ENST00000954843

RefSeq mRNA: 2 — MANE Select: NM_001409 NM_001409, NM_001410718

CCDS: CCDS41237, CCDS90845

Canonical transcript exons

ENST00000356575 — 37 exons

Exon	Start	End
ENSE00001066619	3505208	3505342
ENSE00001066620	3508558	3508689
ENSE00001066621	3505422	3505556
ENSE00001066622	3509870	3509992
ENSE00001066623	3506108	3506236
ENSE00001066625	3509075	3509245
ENSE00001123243	3510783	3510902
ENSE00001123248	3511550	3511687
ENSE00001123255	3512006	3512128
ENSE00001123261	3514550	3514672
ENSE00001123265	3515402	3515527
ENSE00001123278	3524124	3524246
ENSE00001123340	3500966	3501094
ENSE00001123347	3501177	3501308
ENSE00001123358	3501796	3501921
ENSE00001123378	3500633	3500764
ENSE00001123490	3498371	3498499
ENSE00001206786	3499588	3499716
ENSE00001206792	3499796	3499924
ENSE00001321857	3507795	3507923
ENSE00001402691	3579825	3579929
ENSE00001477187	3498698	3498826
ENSE00001477188	3499138	3499266
ENSE00001477189	3595338	3595447
ENSE00001477190	3602466	3602600
ENSE00001477191	3611138	3611508
ENSE00001942491	3487951	3490589
ENSE00003466602	3493996	3494124
ENSE00003527961	3494371	3494499
ENSE00003561382	3497233	3497361
ENSE00003586751	3490912	3490959
ENSE00003639331	3495890	3496018
ENSE00003662297	3496988	3497119
ENSE00003675428	3493771	3493899
ENSE00003676409	3494613	3494741
ENSE00003677545	3492639	3492767
ENSE00003691615	3496655	3496783

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7946 / max 220.0089, expressed in 1178 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9946	3.4018	948
9947	1.5730	390
9945	0.3401	178
9944	0.1597	66
9948	0.1565	63
9942	0.1115	58
9943	0.0521	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	97.61	gold quality
descending thoracic aorta	UBERON:0002345	97.21	gold quality
ascending aorta	UBERON:0001496	97.14	gold quality
thoracic aorta	UBERON:0001515	97.10	gold quality
left coronary artery	UBERON:0001626	95.60	gold quality
skin of abdomen	UBERON:0001416	95.34	gold quality
aorta	UBERON:0000947	95.28	gold quality
left uterine tube	UBERON:0001303	94.98	gold quality
coronary artery	UBERON:0001621	94.84	gold quality
skin of leg	UBERON:0001511	94.74	gold quality
popliteal artery	UBERON:0002250	94.06	gold quality
tibial artery	UBERON:0007610	94.05	gold quality
zone of skin	UBERON:0000014	92.20	gold quality
omental fat pad	UBERON:0010414	90.71	gold quality
peritoneum	UBERON:0002358	90.66	gold quality
vagina	UBERON:0000996	90.31	gold quality
minor salivary gland	UBERON:0001830	90.17	gold quality
upper lobe of left lung	UBERON:0008952	89.88	gold quality
right lung	UBERON:0002167	89.82	gold quality
gall bladder	UBERON:0002110	89.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.41	gold quality
pericardium	UBERON:0002407	89.09	gold quality
upper lobe of lung	UBERON:0008948	88.34	gold quality
mouth mucosa	UBERON:0003729	87.68	gold quality
tendon of biceps brachii	UBERON:0008188	87.37	gold quality
upper leg skin	UBERON:0004262	87.27	gold quality
right ovary	UBERON:0002118	87.11	gold quality
left ovary	UBERON:0002119	87.10	gold quality
saliva-secreting gland	UBERON:0001044	87.09	gold quality
ectocervix	UBERON:0012249	87.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting MEGF6, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4498	99.47	67.42	2360

Literature-anchored findings (GeneRIF, showing 2)

• MEGF6 accelerated Colorectal Cancer cell growth and inhibited apoptosis, and promoted Colorectal Cancer metastasis by inducing the Epithelial-to-Mesenchymal Transition. (PMID:29719292)
• A role for the MEGF6 gene in predisposition to osteoporosis. (PMID:33026655)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	egfem1	ENSDARG00000005216
mus_musculus	Megf6	ENSMUSG00000057751
rattus_norvegicus	Megf6	ENSRNOG00000000156

Paralogs (3): MEGF10 (ENSG00000145794), MEGF11 (ENSG00000157890), GAS6 (ENSG00000183087)

Protein

Protein identifiers

Multiple epidermal growth factor-like domains protein 6 — O75095 (reviewed: O75095)

Alternative names: Epidermal growth factor-like protein 3

All UniProt accessions (4): A0A8V8TL19, O75095, H7C557, H7C5N9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Isoforms (2)

UniProt ID	Names	Canonical?
O75095-1	1	yes
O75095-2	2

RefSeq proteins (2): NP_001397647, NP_001400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002049	LE_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011489	EMI_domain	Domain
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR049883	NOTCH1_EGF-like	Domain
IPR052108	MEGF/SIB	Family

Pfam: PF00053, PF07645, PF12662, PF14670

UniProt features (120 total): disulfide bond 72, domain 28, sequence variant 9, splice variant 5, glycosylation site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75095-F1	70.56	0.00

Functional residue map

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

Disulfide bonds (72): 1387–1399, 1393–1406, 1408–1417, 1473–1485, 1479–1492, 1494–1503, 48–111, 77–83, 110–123, 128–139, 133–147, 149–158, 165–176, 172–185, 187–200, 242–255, 248–268, 270–283, 289–300, 296–309 …

Glycosylation sites (2): 252, 739

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): PEREZ_TP63_TARGETS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, CHANDRAN_METASTASIS_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOZGIT_ESR1_TARGETS_UP, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, PEREZ_TP53_AND_TP63_TARGETS, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, ROSS_AML_WITH_PML_RARA_FUSION, CERVERA_SDHB_TARGETS_1_UP, GOMF_SCAVENGER_RECEPTOR_ACTIVITY, GOMF_CARGO_RECEPTOR_ACTIVITY, chr1p36

GO Biological Process (1): vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): calcium ion binding (GO:0005509), scavenger receptor activity (GO:0005044), protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
cellular process	1
metal ion binding	1
cargo receptor activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEGF6	WRAP73	Q9P2S5	877
MEGF6	ZBTB40	Q9NUA8	763
MEGF6	MFAP5	Q13361	714
MEGF6	CCDC136	Q96JN2	588
MEGF6	IFT122	Q9HBG6	549
MEGF6	CD3D	P04234	504
MEGF6	H7BZ11	H7BZ11	479
MEGF6	CCDC27	Q2M243	452
MEGF6	RITA1	Q96K30	451
MEGF6	USP17L18	D6R9N7	447
MEGF6	CRIM1	Q9NZV1	431
MEGF6	MORN1	Q5T089	426
MEGF6	CTNNAL1	Q9UBT7	416
MEGF6	CELSR2	Q9HCU4	412
MEGF6	CREG1	O75629	410

IntAct

17 interactions, top by confidence:

A	B	Type	Score
MEGF6	EGFR	psi-mi:“MI:0915”(physical association)	0.550
MEGF6	ATXN7	psi-mi:“MI:0915”(physical association)	0.510
MEGF6	CACNA1A	psi-mi:“MI:0915”(physical association)	0.510
ATXN7	MEGF6	psi-mi:“MI:0915”(physical association)	0.510
MEGF6	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
MEGF6	MBD1	psi-mi:“MI:0915”(physical association)	0.370
MEGF6	NUFIP2	psi-mi:“MI:0915”(physical association)	0.370
MEGF6	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
	MEGF6	psi-mi:“MI:0915”(physical association)	0.370
CDH5	MYO1C	psi-mi:“MI:2364”(proximity)	0.270
CRKL	MEGF6	psi-mi:“MI:0915”(physical association)	0.000
ATN1	MEGF6	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	MEGF6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): MEGF6 (Affinity Capture-RNA), MEGF6 (Affinity Capture-MS), MEGF6 (Affinity Capture-MS), MEGF6 (Two-hybrid), MEGF6 (Two-hybrid), MEGF6 (Two-hybrid), MEGF6 (Two-hybrid), MEGF6 (Affinity Capture-RNA), MEGF6 (PCA), MEGF6 (Two-hybrid), MEGF6 (Two-hybrid), MEGF6 (Two-hybrid), MEGF6 (Two-hybrid), MEGF6 (Two-hybrid)

ESM2 similar proteins: A0JM12, A1A5Y0, A2VCU8, A4FV93, A6BM72, A6QR11, B2LW77, D3ZUK3, E9QJQ6, O70534, O75095, O88281, P07174, P15800, P23142, P55268, P80370, P97607, Q14162, Q2VWQ2, Q5ND28, Q5R3Z7, Q5VY43, Q60519, Q61220, Q61292, Q62918, Q62919, Q6DIB5, Q6UXH1, Q6UY11, Q75N90, Q7ZXL5, Q80T14, Q80T91, Q80V70, Q86XX4, Q8C088, Q8K1E3, Q8MJJ9

Diamond homologs: A0A1U9VX91, A2AJ76, O08999, O43897, O57382, O57460, O75095, P13497, P35556, P98063, P98070, P98133, Q00918, Q14766, Q61555, Q62381, Q75N90, Q7KVA1, Q8C088, Q8CG19, Q8JI28, Q9DER7, Q9TV36, A1A5Y0, A2VCU8, A4IGL7, A5A8Y8, A6QR11, B5DFC9, O88322, P07996, P10493, P14585, P35441, P35448, P82279, P98118, Q14112, Q20911, Q24025

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	301
Likely benign	36
Benign	17

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
625767	GRCh37/hg19 1p36.33-36.32(chr1:568708-3662949)	Pathogenic
638116	GRCh37/hg19 1p36.33-36.23(chr1:82154-7637060)x1	Pathogenic

SpliceAI

8396 predictions. Top by Δscore:

Variant	Effect	Δscore
1:3490906:CCTTA:C	donor_loss	1.0000
1:3490907:CTTAC:C	donor_loss	1.0000
1:3490908:TTA:T	donor_loss	1.0000
1:3490909:TAC:T	donor_loss	1.0000
1:3490910:ACCT:A	donor_loss	1.0000
1:3490911:CC:C	donor_loss	1.0000
1:3490958:ACCT:A	acceptor_loss	1.0000
1:3490959:CCTG:C	acceptor_loss	1.0000
1:3490960:CTGGA:C	acceptor_loss	1.0000
1:3490961:T:C	acceptor_loss	1.0000
1:3498370:CGG:C	donor_gain	1.0000
1:3498370:CGGCT:C	donor_gain	1.0000
1:3505341:CT:C	acceptor_gain	1.0000
1:3506106:A:AC	donor_gain	1.0000
1:3506107:C:CC	donor_gain	1.0000
1:3507743:T:TA	donor_gain	1.0000
1:3507744:C:A	donor_gain	1.0000
1:3507765:T:TA	donor_gain	1.0000
1:3507793:ACCAT:A	donor_gain	1.0000
1:3507794:CCATC:C	donor_gain	1.0000
1:3507802:A:AC	donor_gain	1.0000
1:3507803:C:CC	donor_gain	1.0000
1:3507816:TGA:T	donor_gain	1.0000
1:3507920:CAAG:C	acceptor_gain	1.0000
1:3507922:AG:A	acceptor_gain	1.0000
1:3507923:GC:G	acceptor_loss	1.0000
1:3507924:C:CA	acceptor_loss	1.0000
1:3507924:C:CC	acceptor_gain	1.0000
1:3508556:A:AC	donor_gain	1.0000
1:3508557:C:CC	donor_gain	1.0000

AlphaMissense

10118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:3506170:C:G	C619S	0.996
1:3506171:A:T	C619S	0.996
1:3501289:C:A	W778C	0.995
1:3501289:C:G	W778C	0.995
1:3506194:C:G	C611S	0.995
1:3506195:A:T	C611S	0.995
1:3506116:C:G	C637S	0.992
1:3506116:C:T	C637Y	0.992
1:3506117:A:T	C637S	0.992
1:3506233:C:G	C598S	0.992
1:3506234:A:T	C598S	0.992
1:3512011:C:G	C324S	0.992
1:3512012:A:T	C324S	0.992
1:3506188:C:G	C613S	0.991
1:3506189:A:T	C613S	0.991
1:3514555:C:G	C283S	0.991
1:3514556:A:T	C283S	0.991
1:3524213:C:G	C172S	0.991
1:3524214:A:T	C172S	0.991
1:3505526:C:G	C650S	0.990
1:3505527:A:T	C650S	0.990
1:3506126:C:A	G634C	0.990
1:3506171:A:G	C619R	0.990
1:3507803:C:G	C594S	0.990
1:3507804:A:T	C594S	0.990
1:3511627:C:G	C346S	0.990
1:3511628:A:T	C346S	0.990
1:3511660:C:G	C335S	0.990
1:3511661:A:T	C335S	0.990
1:3524201:C:G	C176S	0.990

dbSNP variants (sampled 300 via entrez): RS1000004876 (1:3503695 ATGTATGTG>A), RS1000011796 (1:3584688 G>C), RS1000065158 (1:3524431 T>C), RS1000080764 (1:3487938 A>G), RS1000112118 (1:3590839 A>G,T), RS1000144355 (1:3605808 G>T), RS1000152590 (1:3488142 T>C), RS1000156577 (1:3516309 G>A), RS1000170178 (1:3569625 C>T), RS1000171616 (1:3544225 ACC>A), RS1000221024 (1:3569444 G>A), RS1000228385 (1:3506920 G>A), RS1000230209 (1:3548854 C>A,T), RS1000279575 (1:3528806 G>A), RS1000306962 (1:3541241 G>A)

Disease associations

OMIM: gene MIM:604266 | disease phenotypes: MIM:607872

GenCC curated gene-disease

Mondo (1): chromosome 1p36 deletion syndrome (MONDO:0011929)

Orphanet (1): 1p36 deletion syndrome (Orphanet:1606)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006416_4	Chronic central serous retinopathy	6.000000e-07
GCST011382_6	Systemic mastocytosis	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009363	chronic central serous retinopathy

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535362	Chromosome 1p36 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment, increases expression	4
sodium arsenite	affects methylation, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Tobacco Smoke Pollution	decreases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression, increases methylation	2
Aflatoxin B1	decreases expression, affects methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation, decreases methylation	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)