MEGF9

Summary

MEGF9 (multiple EGF like domains 9, HGNC:3234) is a protein-coding gene on chromosome 9q33.2, encoding Multiple epidermal growth factor-like domains protein 9 (Q9H1U4).

Predicted to be located in basement membrane and membrane.

Source: NCBI Gene 1955 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_001080497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3234
Approved symbol	MEGF9
Name	multiple EGF like domains 9
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106780
Ensembl biotype	protein_coding
OMIM	604268
Entrez	1955

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000373930, ENST00000863479, ENST00000863480

RefSeq mRNA: 1 — MANE Select: NM_001080497 NM_001080497

CCDS: CCDS48010

Canonical transcript exons

ENST00000373930 — 6 exons

Exon	Start	End
ENSE00000723913	120600811	120605641
ENSE00000723914	120607741	120608010
ENSE00000723915	120612396	120612539
ENSE00000723919	120622616	120622755
ENSE00000723923	120659374	120659575
ENSE00001461944	120713758	120714470

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8211 / max 1665.9787, expressed in 1694 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102299	13.7165	1673
102297	0.9438	320
102298	0.5084	203
102300	0.2137	81
102296	0.1768	59
102295	0.1625	53
102294	0.0994	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	98.95	gold quality
trigeminal ganglion	UBERON:0001675	98.35	gold quality
dorsal root ganglion	UBERON:0000044	97.42	gold quality
monocyte	CL:0000576	97.25	gold quality
mononuclear cell	CL:0000842	97.23	gold quality
leukocyte	CL:0000738	96.98	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.97	gold quality
lateral globus pallidus	UBERON:0002476	96.87	gold quality
subthalamic nucleus	UBERON:0001906	96.85	gold quality
substantia nigra pars compacta	UBERON:0001965	96.48	gold quality
trabecular bone tissue	UBERON:0002483	96.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.24	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.24	gold quality
inferior vagus X ganglion	UBERON:0005363	95.68	gold quality
CA1 field of hippocampus	UBERON:0003881	95.60	gold quality
superior vestibular nucleus	UBERON:0007227	95.41	gold quality
pigmented layer of retina	UBERON:0001782	95.22	gold quality
medulla oblongata	UBERON:0001896	95.17	gold quality
pons	UBERON:0000988	94.90	gold quality
postcentral gyrus	UBERON:0002581	94.71	gold quality
globus pallidus	UBERON:0001875	94.64	gold quality
blood	UBERON:0000178	94.53	gold quality
hair follicle	UBERON:0002073	94.40	gold quality
parietal lobe	UBERON:0001872	94.27	gold quality
cortical plate	UBERON:0005343	94.26	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.24	gold quality
orbitofrontal cortex	UBERON:0004167	94.15	gold quality
medial globus pallidus	UBERON:0002477	94.02	gold quality
corpus callosum	UBERON:0002336	93.74	gold quality
inferior olivary complex	UBERON:0002127	93.58	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	20.44
E-ANND-3	yes	16.56
E-MTAB-9067	yes	13.38
E-MTAB-9801	yes	6.87
E-MTAB-7303	no	168.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

183 targeting MEGF9, 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-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-7110-3P	100.00	73.18	2486
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-150-5P	99.99	66.69	1976
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693

Literature-anchored findings (GeneRIF, showing 2)

• miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-alpha, CCNJ, and MEGF9. (PMID:24098452)
• miR-7/EGFR/MEGF9 axis regulates cartilage degradation in osteoarthritis via PI3K/AKT/mTOR signaling pathway. (PMID:34629037)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Megf9	ENSMUSG00000039270
rattus_norvegicus	Megf9	ENSRNOG00000005932

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN1 (ENSG00000065320), NTN4 (ENSG00000074527), ATRN (ENSG00000088812), LAMB4 (ENSG00000091128), LAMB1 (ENSG00000091136), LAMA1 (ENSG00000101680), MEGF8 (ENSG00000105429), ATRNL1 (ENSG00000107518), LAMA4 (ENSG00000112769), LAMA5 (ENSG00000130702), LAMC1 (ENSG00000135862), NTN5 (ENSG00000142233), HSPG2 (ENSG00000142798), TMEFF2 (ENSG00000144339), NTN3 (ENSG00000162068), NTNG1 (ENSG00000162631), EGFLAM (ENSG00000164318), LAMB2 (ENSG00000172037), AGRN (ENSG00000188157), NTNG2 (ENSG00000196358), LAMA2 (ENSG00000196569), LAMB3 (ENSG00000196878), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Multiple epidermal growth factor-like domains protein 9 — Q9H1U4 (reviewed: Q9H1U4)

Alternative names: Epidermal growth factor-like protein 5

All UniProt accessions (1): Q9H1U4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Polymorphism. The poly-Ala stretch (positions 24 to 31) may be polymorphic and varies from 6 to 8 Ala residues.

RefSeq proteins (1): NP_001073966* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002049	LE_dom	Domain
IPR050440	Laminin/Netrin_ECM	Family
IPR056863	LMN_ATRN_NET-like_EGF	Domain

Pfam: PF00053, PF24973

UniProt features (46 total): disulfide bond 20, glycosylation site 11, domain 5, compositionally biased region 4, topological domain 2, signal peptide 1, chain 1, region of interest 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1U4-F1	67.32	0.35

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 (20): 204–217, 206–224, 226–235, 238–251, 254–266, 256–272, 274–283, 286–298, 301–310, 303–317, 320–329, 332–346, 349–360, 351–371, 374–383, 386–397, 400–415, 402–422, 425–434, 437–449

Glycosylation sites (11): 40, 182, 205, 218, 245, 267, 305, 428, 468, 481, 500

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 229 (showing top): GCM_PTPRD, MODULE_45, HALMOS_CEBPA_TARGETS_UP, MODULE_66, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, SCHLOSSER_SERUM_RESPONSE_DN, MASSARWEH_RESPONSE_TO_ESTRADIOL, CLAUS_PGR_POSITIVE_MENINGIOMA_DN, BASAKI_YBX1_TARGETS_DN, GOCC_BASEMENT_MEMBRANE, MODULE_11, HUANG_DASATINIB_RESISTANCE_DN, GCM_PTK2

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): basement membrane (GO:0005604), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular matrix	1
cellular anatomical structure	1

Protein interactions and networks

STRING

400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEGF9	EGF	P01133	591
MEGF9	CCNJ	Q5T5M9	571
MEGF9	DLK2	Q6UY11	483
MEGF9	EGFL6	Q8IUX8	449
MEGF9	EGFL8	Q99944	439
MEGF9	SLC67A1-AS	Q8N1D0	394
MEGF9	ENPEP	Q07075	370
MEGF9	CSNK2A2	P19784	358
MEGF9	ZBTB38	Q8NAP3	355
MEGF9	NHSL3	Q9P206	355
MEGF9	EGFL7	Q9UHF1	318
MEGF9	UEVLD	Q8IX04	284
MEGF9	TIGD2	Q4W5G0	277
MEGF9	PRRC1	Q96M27	270
MEGF9	CDK5RAP2	Q96SN8	269
MEGF9	MEGF6	O75095	269

IntAct

7 interactions, top by confidence:

A	B	Type	Score
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
MYH4	PALM3	psi-mi:“MI:0914”(association)	0.350
MEGF9	TCAF2	psi-mi:“MI:0914”(association)	0.350
MYH4	MYH7	psi-mi:“MI:0914”(association)	0.350
DYRK1A	MEGF9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): MEGF9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), MEGF9 (Affinity Capture-MS), FAM115C (Affinity Capture-MS), MEGF9 (Positive Genetic), MEGF9 (Two-hybrid), MEGF9 (Proximity Label-MS), MEGF9 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1F4, A7SXG9, A8X481, A8X9H4, B3EX01, B7YZU2, B7Z0W9, F5HB98, O16883, O45599, P03200, P07562, P11450, P15269, P16833, P26261, P28968, P32515, P34468, P42287, P68326, P68329, P68343, P68344, P81282, P98159, Q03345, Q04164, Q05319, Q09337, Q09457, Q09624, Q1LY77, Q1XI86, Q28858, Q3KST4, Q5XI62, Q6DLD8, Q6R0H7, Q6UDF7

Diamond homologs: A0JP86, A2ASQ1, G5ECE3, O00468, O00634, O09118, O15230, O75445, O75882, O95631, P02468, P11047, P15215, P19137, P24043, P25304, P25391, P31696, P34710, P97927, Q00174, Q01635, Q13751, Q13753, Q16363, Q16787, Q18823, Q19981, Q1LVF0, Q24567, Q24568, Q27262, Q2HXW4, Q2QI47, Q5RB89, Q5VV63, Q60675, Q61001, Q61087, Q61092

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1673 predictions. Top by Δscore:

Variant	Effect	Δscore
9:120608006:CGATT:C	acceptor_gain	1.0000
9:120608009:TT:T	acceptor_gain	1.0000
9:120608009:TTC:T	acceptor_loss	1.0000
9:120608010:TCTA:T	acceptor_loss	1.0000
9:120608011:C:CC	acceptor_gain	1.0000
9:120608011:C:T	acceptor_loss	1.0000
9:120608012:T:A	acceptor_loss	1.0000
9:120612389:GCCTT:G	donor_loss	1.0000
9:120612390:CCTTA:C	donor_loss	1.0000
9:120612391:CTTA:C	donor_loss	1.0000
9:120612392:TTA:T	donor_loss	1.0000
9:120612393:TA:T	donor_loss	1.0000
9:120612394:A:AC	donor_gain	1.0000
9:120612394:AC:A	donor_loss	1.0000
9:120612395:C:CA	donor_gain	1.0000
9:120612395:CTT:C	donor_gain	1.0000
9:120612395:CTTA:C	donor_gain	1.0000
9:120612398:A:AC	donor_gain	1.0000
9:120612399:T:C	donor_gain	1.0000
9:120612538:ACC:A	acceptor_loss	1.0000
9:120612540:CTAA:C	acceptor_loss	1.0000
9:120612541:T:C	acceptor_loss	1.0000
9:120622612:GTA:G	donor_loss	1.0000
9:120622613:TACCT:T	donor_loss	1.0000
9:120622614:A:AC	donor_gain	1.0000
9:120622614:A:AT	donor_loss	1.0000
9:120622614:AC:A	donor_gain	1.0000
9:120622615:C:CC	donor_gain	1.0000
9:120622615:CC:C	donor_gain	1.0000
9:120622615:CCT:C	donor_gain	1.0000

AlphaMissense

3909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:120605313:G:C	F562L	0.999
9:120605313:G:T	F562L	0.999
9:120605315:A:G	F562L	0.999
9:120605326:T:A	D558V	0.999
9:120605329:T:A	E557V	0.999
9:120605332:T:A	K556I	0.999
9:120605335:A:G	L555P	0.999
9:120605341:A:T	I553N	0.999
9:120605346:C:A	W551C	0.999
9:120605346:C:G	W551C	0.999
9:120605348:A:G	W551R	0.999
9:120605348:A:T	W551R	0.999
9:120605411:C:G	G530R	0.999
9:120605411:C:T	G530R	0.999
9:120605469:C:A	W510C	0.999
9:120605469:C:G	W510C	0.999
9:120605307:G:C	S564R	0.998
9:120605307:G:T	S564R	0.998
9:120605309:T:G	S564R	0.998
9:120605314:A:C	F562C	0.998
9:120605316:A:C	S561R	0.998
9:120605316:A:T	S561R	0.998
9:120605318:T:G	S561R	0.998
9:120605320:A:G	I560T	0.998
9:120605341:A:C	I553S	0.998
9:120605350:A:C	F550C	0.998
9:120605383:C:G	R539P	0.998
9:120605410:C:T	G530E	0.998
9:120605413:A:C	M529R	0.998
9:120605413:A:T	M529K	0.998

dbSNP variants (sampled 300 via entrez): RS1000093419 (9:120629607 C>A), RS1000098140 (9:120650545 A>G), RS1000112513 (9:120627938 T>C), RS1000147236 (9:120624668 A>T), RS1000177129 (9:120647609 G>A), RS1000207558 (9:120628471 T>G), RS1000234572 (9:120698630 C>A), RS1000235289 (9:120667220 G>A), RS1000255942 (9:120602205 T>C), RS1000271720 (9:120609630 T>C), RS1000317567 (9:120676611 T>G), RS1000365776 (9:120631375 A>C,G), RS1000388089 (9:120609286 A>C,G), RS1000429999 (9:120629862 G>A,C), RS1000439493 (9:120704412 A>C)

Disease associations

OMIM: gene MIM:604268 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000635_5	Response to statin therapy	1.000000e-06
GCST004748_11	Lung cancer	3.000000e-06
GCST008839_369	Height	4.000000e-09
GCST009391_644	Metabolite levels	8.000000e-06
GCST010244_192	Triglyceride levels	3.000000e-08
GCST012447_2	Anxiety x maternal smoking during pregnancy interaction	1.000000e-07
GCST012449_2	Anxiety	5.000000e-07
GCST90002385_394	High light scatter reticulocyte count	3.000000e-14
GCST90002386_437	High light scatter reticulocyte percentage of red cells	7.000000e-15
GCST90002405_470	Reticulocyte count	7.000000e-13
GCST90002406_285	Reticulocyte fraction of red cells	4.000000e-14
GCST90020028_368	Hip circumference adjusted for BMI	4.000000e-10
GCST90020028_369	Hip circumference adjusted for BMI	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010504	inositol measurement
EFO:0004530	triglyceride measurement
EFO:0007986	reticulocyte count
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
lead acetate	increases expression	1
afimoxifene	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
cupric chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Bilirubin	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Methotrexate	affects response to substance	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Phthalic Acids	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression, increases abundance	1
Tretinoin	increases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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