MEGF11

Summary

MEGF11 (multiple EGF like domains 11, HGNC:29635) is a protein-coding gene on chromosome 15q22.31, encoding Multiple epidermal growth factor-like domains protein 11 (A6BM72). May regulate the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion.

Predicted to be involved in homotypic cell-cell adhesion and retina layer formation. Predicted to be located in basolateral plasma membrane.

Source: NCBI Gene 84465 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 200 total
• MANE Select transcript: NM_001385028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29635
Approved symbol	MEGF11
Name	multiple EGF like domains 11
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1781, DKFZp434L121
Ensembl gene	ENSG00000157890
Ensembl biotype	protein_coding
OMIM	612454
Entrez	84465

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000288745, ENST00000395614, ENST00000409699, ENST00000422354, ENST00000455812, ENST00000469917, ENST00000474398, ENST00000478590, ENST00000478721, ENST00000484618, ENST00000489275, ENST00000490495, ENST00000493192, ENST00000562154, ENST00000564573, ENST00000858878

RefSeq mRNA: 9 — MANE Select: NM_001385028 NM_001385028, NM_001385029, NM_001385030, NM_001385031, NM_001385032, NM_001385033, NM_001387150, NM_001387151, NM_032445

CCDS: CCDS10213, CCDS92026, CCDS92027

Canonical transcript exons

ENST00000395614 — 26 exons

Exon	Start	End
ENSE00003505541	65898728	65898934
ENSE00003516047	66128306	66128411
ENSE00003519926	65970553	65970689
ENSE00003535542	65909740	65909806
ENSE00003596777	65895299	65898094
ENSE00003600338	65906085	65906141
ENSE00003666088	65915470	65915598
ENSE00003713154	65916148	65916276
ENSE00003713485	65928425	65928527
ENSE00003716893	66119086	66119186
ENSE00003719757	65917966	65918094
ENSE00003719836	65982242	65982488
ENSE00003726307	65916828	65916956
ENSE00003728825	65913737	65913973
ENSE00003729909	65980778	65980898
ENSE00003731427	65957547	65957721
ENSE00003733555	65922338	65922472
ENSE00003738020	65964908	65965120
ENSE00003742128	65929720	65929883
ENSE00003744212	65930823	65930943
ENSE00003744998	65912082	65912200
ENSE00003747630	66123899	66124000
ENSE00003747941	66094402	66094494
ENSE00003749598	65922823	65922969
ENSE00003752415	65909034	65909135
ENSE00003921038	66253605	66253750

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 94.16.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4419 / max 134.5065, expressed in 238 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150585	1.1099	193
150587	0.2147	96
150586	0.0804	42
150579	0.0226	11
150574	0.0092	3
150573	0.0026	2
150575	0.0025	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	94.16	gold quality
cerebellum	UBERON:0002037	94.11	gold quality
cerebellar cortex	UBERON:0002129	94.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.33	gold quality
amygdala	UBERON:0001876	85.41	gold quality
hypothalamus	UBERON:0001898	84.14	gold quality
Ammon’s horn	UBERON:0001954	83.77	gold quality
cerebellar vermis	UBERON:0004720	82.18	silver quality
anterior cingulate cortex	UBERON:0009835	80.92	gold quality
cortical plate	UBERON:0005343	80.65	gold quality
right uterine tube	UBERON:0001302	80.43	gold quality
substantia nigra	UBERON:0002038	80.29	gold quality
left testis	UBERON:0004533	80.16	gold quality
right testis	UBERON:0004534	79.88	gold quality
temporal lobe	UBERON:0001871	78.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.30	gold quality
midbrain	UBERON:0001891	78.20	gold quality
brain	UBERON:0000955	77.80	gold quality
right frontal lobe	UBERON:0002810	77.39	gold quality
spinal cord	UBERON:0002240	76.97	gold quality
adenohypophysis	UBERON:0002196	76.86	gold quality
testis	UBERON:0000473	76.68	gold quality
nucleus accumbens	UBERON:0001882	76.68	gold quality
pons	UBERON:0000988	76.04	gold quality
cerebral cortex	UBERON:0000956	75.83	gold quality
caudate nucleus	UBERON:0001873	75.83	gold quality
forebrain	UBERON:0001890	75.70	gold quality
tibia	UBERON:0000979	75.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.98	silver quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1274.05
E-HCAD-35	yes	73.81
E-GEOD-84465	yes	29.10
E-HCAD-25	yes	23.86
E-GEOD-93593	yes	5.34
E-ANND-3	no	4.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

204 targeting MEGF11, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 2)

• Overexpression of multiple epidermal growth factor like domains 11 rescues anoikis survival through tumor cells-platelet interaction in triple negative breast Cancer cells. (PMID:35398017)
• Prenatal phthalate exposure and cord blood DNA methylation. (PMID:37120575)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	megf11	ENSDARG00000062686
mus_musculus	Megf11	ENSMUSG00000036466
rattus_norvegicus	Megf11	ENSRNOG00000010634

Paralogs (3): MEGF10 (ENSG00000145794), MEGF6 (ENSG00000162591), GAS6 (ENSG00000183087)

Protein

Protein identifiers

Multiple epidermal growth factor-like domains protein 11 — A6BM72 (reviewed: A6BM72)

All UniProt accessions (6): A0A087WT97, A0A087X003, A0A0A0MS64, A6BM72, C9JYE7, H3BR81

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion. Mosaics provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements.

Subunit / interactions. Homomer. Does not interact with MEGF10.

Subcellular location. Cell membrane. Basolateral cell membrane.

Similarity. Belongs to the MEGF family.

Isoforms (4)

UniProt ID	Names	Canonical?
A6BM72-1	1	yes
A6BM72-2	2
A6BM72-3	3
A6BM72-4	4

RefSeq proteins (9): NP_001371957, NP_001371958, NP_001371959, NP_001371960, NP_001371961, NP_001371962, NP_001374079, NP_001374080, NP_115821 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002049	LE_dom	Domain
IPR011489	EMI_domain	Domain
IPR013032	EGF-like_CS	Conserved_site
IPR052485	MEGF_diff_regulators	Family
IPR057138	EGF_PEAR1L-like	Domain

Pfam: PF00053, PF12661, PF23106, PF23301

UniProt features (81 total): disulfide bond 44, domain 15, splice variant 7, sequence variant 6, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6BM72-F1	74.12	0.04

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 (44): 28–89, 54–63, 88–99, 103–118, 120–129, 146–154, 148–161, 163–172, 185–197, 191–204, 206–215, 228–240, 234–247, 249–258, 271–283, 277–290, 292–301, 314–326, 320–333, 335–344 …

Glycosylation sites (2): 270, 531

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_CELL_CELL_ADHESION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, RICKMAN_METASTASIS_DN, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, IRF1_Q6, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_RETINA_LAYER_FORMATION, GOBP_HOMOTYPIC_CELL_CELL_ADHESION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_BASEMENT_MEMBRANE, GOBP_SENSORY_ORGAN_MORPHOGENESIS, GOBP_CELL_SUBSTRATE_ADHESION, MODULE_48, GOBP_RETINA_DEVELOPMENT_IN_CAMERA_TYPE_EYE

GO Biological Process (2): retina layer formation (GO:0010842), homotypic cell-cell adhesion (GO:0034109)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): basolateral plasma membrane (GO:0016323), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neural retina development	1
anatomical structure formation involved in morphogenesis	1
retina morphogenesis in camera-type eye	1
cell-cell adhesion	1
binding	1
basal plasma membrane	1
plasma membrane region	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEGF11	IFT122	Q9HBG6	723
MEGF11	CCDC136	Q96JN2	609
MEGF11	CCDC117	Q8IWD4	596
MEGF11	EGF	P01133	595
MEGF11	VEPH1	Q14D04	532
MEGF11	ATN1	P54259	472
MEGF11	GULP1	Q9UBP9	465
MEGF11	METTL21C	Q5VZV1	449
MEGF11	RITA1	Q96K30	447
MEGF11	LMAN1L	Q9HAT1	443
MEGF11	DMRT3	Q9NQL9	427
MEGF11	NTNG1	Q9Y2I2	422
MEGF11	NINL	Q9Y2I6	418
MEGF11	GLT1D1	Q96MS3	418
MEGF11	OR8U1	Q8NH10	410

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MEGF11	NUFIP2	psi-mi:“MI:0915”(physical association)	0.560
MEGF11	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
NUFIP2	MEGF11	psi-mi:“MI:0915”(physical association)	0.000
ATN1	MEGF11	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): MEGF11 (Proximity Label-MS), MEGF11 (Protein-RNA), MEGF11 (Two-hybrid), MEGF11 (Two-hybrid), MEGF11 (Two-hybrid)

ESM2 similar proteins: A0JM12, A1A5Y0, A2VCU8, A6BM72, A6QR11, E9QJQ6, O42182, O70534, O88281, P23142, P35555, P35953, P80370, P97607, P98133, P98155, P98156, P98165, P98166, Q08879, Q09163, Q28832, Q2VWQ2, Q5R3Z7, Q5VY43, Q61220, Q61554, Q61555, Q62918, Q62919, Q6DIB5, Q7ZXL5, Q80T14, Q80T91, Q80V70, Q86XX4, Q8C088, Q8R4Y4, Q8VIK5, Q90827

Diamond homologs: A0JM12, A6BM72, A8XMW6, E9QJQ6, Q5ND28, Q5RBP1, Q5VY43, Q6DIB5, Q6UXI9, Q80T91, Q8AVH7, Q8VIK5, Q91V88, Q96KG7, Q9W0A0, Q9XWD6, Q99944, Q8IUX8, Q9JJZ5, P59222, Q14162, Q6AZ60, Q96GP6, A2AJ76, A2RUV0, A2VCU8, A5A8Y8, A6QR11, A8WGB1, B3EWY9, B5DFC9, G3I6Z6, G3V928, O42182, O73775, O75095, O77469, O88322, P10493, P21783

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	182
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

7056 predictions. Top by Δscore:

Variant	Effect	Δscore
15:65906157:A:C	acceptor_gain	1.0000
15:65913731:CCTTA:C	donor_loss	1.0000
15:65913732:CTTAC:C	donor_loss	1.0000
15:65913733:TTA:T	donor_loss	1.0000
15:65913734:TACC:T	donor_loss	1.0000
15:65913735:ACCTG:A	donor_loss	1.0000
15:65913736:C:CA	donor_loss	1.0000
15:65913858:CACAA:C	acceptor_gain	1.0000
15:65913969:GGCAG:G	acceptor_gain	1.0000
15:65913970:GCAG:G	acceptor_gain	1.0000
15:65913971:CAG:C	acceptor_gain	1.0000
15:65913971:CAGC:C	acceptor_gain	1.0000
15:65913972:AG:A	acceptor_gain	1.0000
15:65913972:AGCT:A	acceptor_loss	1.0000
15:65913973:GCTG:G	acceptor_loss	1.0000
15:65913974:C:CC	acceptor_gain	1.0000
15:65913974:C:T	acceptor_loss	1.0000
15:65913975:T:A	acceptor_loss	1.0000
15:65915595:CATC:C	acceptor_gain	1.0000
15:65915599:CTGT:C	acceptor_loss	1.0000
15:65915600:T:C	acceptor_loss	1.0000
15:65916146:A:AC	donor_gain	1.0000
15:65916147:C:CC	donor_gain	1.0000
15:65916147:CT:C	donor_gain	1.0000
15:65916147:CTCTG:C	donor_gain	1.0000
15:65928523:CCATC:C	acceptor_gain	1.0000
15:65928524:CATC:C	acceptor_gain	1.0000
15:65928524:CATCC:C	acceptor_gain	1.0000
15:65928525:ATC:A	acceptor_gain	1.0000
15:65928525:ATCC:A	acceptor_loss	1.0000

AlphaMissense

7558 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:65915478:C:G	C822S	0.999
15:65915479:A:T	C822S	0.999
15:65982469:C:A	W138C	0.999
15:65982469:C:G	W138C	0.999
15:66094424:C:A	W124C	0.999
15:66094424:C:G	W124C	0.999
15:66119124:C:G	C88S	0.999
15:66119125:A:G	C88R	0.999
15:66119125:A:T	C88S	0.999
15:66123911:C:G	C63S	0.999
15:66123912:A:G	C63R	0.999
15:66123912:A:T	C63S	0.999
15:66123938:C:G	C54S	0.999
15:66123939:A:G	C54R	0.999
15:66123939:A:T	C54S	0.999
15:66128311:C:A	W31C	0.999
15:66128311:C:G	W31C	0.999
15:65915477:A:C	C822W	0.998
15:65915478:C:A	C822F	0.998
15:65915478:C:T	C822Y	0.998
15:65915479:A:G	C822R	0.998
15:65915510:A:C	C811W	0.998
15:65915511:C:G	C811S	0.998
15:65915512:A:G	C811R	0.998
15:65915512:A:T	C811S	0.998
15:65915518:C:A	G809C	0.998
15:65916835:G:C	C736W	0.998
15:65980781:C:A	W253C	0.998
15:65980781:C:G	W253C	0.998
15:65982258:C:A	G209C	0.998

dbSNP variants (sampled 300 via entrez): RS1000006473 (15:65985287 T>C), RS1000009234 (15:66236284 T>C), RS1000013188 (15:66122802 A>G), RS1000020435 (15:65899017 A>T), RS1000026551 (15:66026001 C>T), RS1000031763 (15:66116910 A>T), RS1000044482 (15:66242161 C>A,G,T), RS1000052262 (15:66154950 C>A,T), RS1000058982 (15:66066612 C>T), RS1000062804 (15:66178887 T>C), RS1000070961 (15:65914119 C>A), RS1000084331 (15:65905101 C>T), RS1000101368 (15:66217423 C>G), RS1000104281 (15:65895090 A>G), RS1000112955 (15:66101880 G>A,T)

Disease associations

OMIM: gene MIM:612454 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010988_202	Adult body size	2.000000e-08
GCST012090_7	Major depressive disorder (MTAG)	4.000000e-08
GCST012335_1	Hodgkin’s lymphoma	1.000000e-12
GCST012490_165	Femur bone mineral density x serum urate levels interaction	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	4
Benzo(a)pyrene	affects methylation, decreases methylation	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic	affects methylation	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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