EGFL8

Summary

EGFL8 (EGF like domain multiple 8, HGNC:13944) is a protein-coding gene on chromosome 6p21.32, encoding Epidermal growth factor-like protein 8 (Q99944).

Predicted to enable signaling receptor binding activity. Predicted to be involved in vasculogenesis. Predicted to be active in cell surface and extracellular region.

Source: NCBI Gene 80864 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_030652

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13944
Approved symbol	EGFL8
Name	EGF like domain multiple 8
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	NG3
Ensembl gene	ENSG00000241404
Ensembl biotype	protein_coding
OMIM	609897
Entrez	80864

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000333845, ENST00000395512, ENST00000432129, ENST00000466239, ENST00000482938, ENST00000489721, ENST00000910328, ENST00000910329, ENST00000942822, ENST00000942823, ENST00000942824, ENST00000942825, ENST00000942826

RefSeq mRNA: 1 — MANE Select: NM_030652 NM_030652

CCDS: CCDS4743

Canonical transcript exons

ENST00000333845 — 9 exons

Exon	Start	End
ENSE00002223604	32164595	32164657
ENSE00003517523	32167910	32168281
ENSE00003546688	32166701	32166810
ENSE00003551966	32166910	32167005
ENSE00003604859	32167350	32167429
ENSE00003623358	32166138	32166266
ENSE00003659594	32167087	32167257
ENSE00003672529	32166498	32166620
ENSE00003783992	32167503	32167656

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 98.87.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0115 / max 55.8194, expressed in 301 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67116	0.9326	271
67117	0.0789	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	98.87	gold quality
lower esophagus mucosa	UBERON:0035834	98.04	gold quality
sural nerve	UBERON:0015488	96.82	gold quality
left ovary	UBERON:0002119	95.46	gold quality
right ovary	UBERON:0002118	95.25	gold quality
ovary	UBERON:0000992	94.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.51	gold quality
cerebellar cortex	UBERON:0002129	93.43	gold quality
cerebellar hemisphere	UBERON:0002245	93.43	gold quality
endocervix	UBERON:0000458	93.39	gold quality
cerebellum	UBERON:0002037	93.36	gold quality
left uterine tube	UBERON:0001303	92.86	gold quality
right uterine tube	UBERON:0001302	92.76	gold quality
body of uterus	UBERON:0009853	92.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.93	gold quality
vagina	UBERON:0000996	91.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.47	gold quality
ectocervix	UBERON:0012249	91.46	gold quality
fundus of stomach	UBERON:0001160	91.26	gold quality
skin of leg	UBERON:0001511	91.26	gold quality
metanephros cortex	UBERON:0010533	91.05	gold quality
mucosa of stomach	UBERON:0001199	91.02	gold quality
zone of skin	UBERON:0000014	91.01	gold quality
skin of abdomen	UBERON:0001416	90.79	gold quality
lower esophagus	UBERON:0013473	90.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.71	gold quality
uterine cervix	UBERON:0000002	90.61	gold quality
esophagus mucosa	UBERON:0002469	90.40	gold quality
esophagus	UBERON:0001043	90.29	gold quality
right coronary artery	UBERON:0001625	90.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	11.13
E-ANND-3	no	1.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting EGFL8, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-3126-3P	97.17	66.51	468
HSA-MIR-4727-3P	96.75	64.97	415
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020
HSA-MIR-6805-5P	95.79	64.86	670
HSA-MIR-4278	95.28	65.49	351

Literature-anchored findings (GeneRIF, showing 5)

• Reduced expression of EGFL8 is closely related to metastastic potential and poor prognosis of CRC, suggesting the down-regulation of EGFL8 as a novel prognostic biomarker for CRC patients. (PMID:21737648)
• The down-regulation of EGFL8 might be a novel biomarker for advanced gastric cancer. (PMID:21965749)
• Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8. (PMID:33712610)
• Down-regulation of EGFL8 regulates migration, invasion and apoptosis of hepatocellular carcinoma through activating Notch signaling pathway. (PMID:34130659)
• Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities. (PMID:34626176)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Egfl8	ENSMUSG00000015467
rattus_norvegicus	Egfl8	ENSRNOG00000000436

Paralogs (5): CFC1 (ENSG00000136698), CFC1B (ENSG00000152093), EGFL7 (ENSG00000172889), CRIPTO3 (ENSG00000225366), CRIPTO (ENSG00000241186)

Protein

Protein identifiers

Epidermal growth factor-like protein 8 — Q99944 (reviewed: Q99944)

Alternative names: Vascular endothelial statin-2

All UniProt accessions (3): Q99944, A0A1U9X7N9, Q5JP22

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

RefSeq proteins (1): NP_085155* (*=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
IPR011489	EMI_domain	Domain
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR049883	NOTCH1_EGF-like	Domain
IPR050969	Dev_Signal_Modulators	Family

Pfam: PF00008, PF07546, PF07645

UniProt features (20 total): disulfide bond 9, sequence variant 3, domain 3, signal peptide 1, chain 1, sequence conflict 1, coiled-coil region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99944-F1	76.30	0.42

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 (9): 114–124, 118–130, 132–141, 148–159, 155–168, 170–183, 38–97, 65–71, 96–110

Glycosylation sites (1): 50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOCC_CELL_SURFACE, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_VASCULOGENESIS, GOBP_EMBRYO_DEVELOPMENT, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_TUBE_MORPHOGENESIS, GOBP_TUBE_DEVELOPMENT, GREB1_TARGET_GENES, MIR548AR_3P, MIR548F_3P, MIR548BC, MIR548AZ_3P

GO Biological Process (1): vasculogenesis (GO:0001570)

GO Molecular Function (3): signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), cell surface (GO:0009986)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell differentiation	1
blood vessel morphogenesis	1
protein binding	1
metal ion binding	1
binding	1

Protein interactions and networks

STRING

748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EGFL8	GPSM3	Q9Y4H4	721
EGFL8	DXO	O77932	620
EGFL8	EGF	P01133	612
EGFL8	C10orf105	Q8TEF2	582
EGFL8	PPT2	Q9UMR5	550
EGFL8	FKBPL	Q9UIM3	545
EGFL8	DLK2	Q6UY11	507
EGFL8	PRRT1	Q99946	506
EGFL8	MEGF9	Q9H1U4	439
EGFL8	BAG6	P46379	372
EGFL8	AGPAT1	Q99943	364
EGFL8	CELSR2	Q9HCU4	348
EGFL8	ATF6B	Q99941	343
EGFL8	HNRNPU	Q00839	328
EGFL8	RNF39	Q9H2S5	322

IntAct

44 interactions, top by confidence:

A	B	Type	Score
EGFL8	CRYAA	psi-mi:“MI:0915”(physical association)	0.610
CRYAA	EGFL8	psi-mi:“MI:0915”(physical association)	0.610
EGFL8		psi-mi:“MI:0915”(physical association)	0.560
	EGFL8	psi-mi:“MI:0915”(physical association)	0.560
CALR	EGFL8	psi-mi:“MI:0915”(physical association)	0.560
EGFL8	DLST	psi-mi:“MI:0915”(physical association)	0.560
EGFL8	ATN1	psi-mi:“MI:0915”(physical association)	0.560
F13A1	EGFL8	psi-mi:“MI:0915”(physical association)	0.560
EGFL8	HSPD1	psi-mi:“MI:0915”(physical association)	0.560
EGFL8	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
VWF	EGFL8	psi-mi:“MI:0915”(physical association)	0.560
EGFL8	JPH3	psi-mi:“MI:0915”(physical association)	0.560
EGFL8	NEK7	psi-mi:“MI:0915”(physical association)	0.560
EGFL8	F13A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (62): KRTAP10-3 (Two-hybrid), CCPG1 (Affinity Capture-MS), FBXO28 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), SLC4A7 (Affinity Capture-MS), LIME1 (Affinity Capture-MS), EGFL7 (Affinity Capture-MS), FBXO28 (Affinity Capture-MS), SLC4A7 (Affinity Capture-MS), EGFL7 (Affinity Capture-MS), LIME1 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), EGFL8 (Affinity Capture-RNA), EGFL8 (Affinity Capture-RNA)

ESM2 similar proteins: A2VEC9, O08644, O08852, O15197, O55225, O88839, O95428, O97507, P00748, P07204, P0C0K6, P0C0K7, P15306, P26010, P26011, P60882, P98140, P98167, Q00657, Q04912, Q04962, Q0V8J4, Q13444, Q2PC93, Q3U492, Q4G0T1, Q5IJ48, Q6GUQ1, Q6MG64, Q6MG84, Q6UVK1, Q6ZRI0, Q6ZWJ8, Q700K0, Q71U07, Q769J6, Q76LX8, Q7Z7M0, Q80YA8, Q8CG65

Diamond homologs: A1A5Y0, A2VCU8, A4IGL7, A5A8Y8, A6QR11, B5DFC9, O75095, O88322, P07996, P10493, P14585, P35441, P35448, P82279, P98118, Q14112, Q20911, Q24025, Q28178, Q2PC93, Q2VWQ2, Q3MHH9, Q5FW85, Q5R3Z7, Q61220, Q62918, Q62919, Q6AZ60, Q6GUQ1, Q6MG84, Q75N90, Q7T3Q2, Q7ZXL5, Q80T14, Q8AVH7, Q8AWW5, Q8VHS2, Q90827, Q90ZD5, Q91X17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1701 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32166485:G:A	acceptor_gain	1.0000
6:32166488:A:AG	acceptor_gain	1.0000
6:32166488:AT:A	acceptor_gain	1.0000
6:32166488:ATG:A	acceptor_gain	1.0000
6:32166489:T:G	acceptor_gain	1.0000
6:32166489:T:TA	acceptor_gain	1.0000
6:32166908:A:AG	acceptor_gain	1.0000
6:32166909:G:GG	acceptor_gain	1.0000
6:32166909:GCC:G	acceptor_gain	1.0000
6:32166989:G:T	donor_gain	1.0000
6:32167002:GTGG:G	donor_gain	1.0000
6:32167004:GG:G	donor_gain	1.0000
6:32167005:GG:G	donor_gain	1.0000
6:32167255:CCGG:C	donor_loss	1.0000
6:32167255:CCGGT:C	donor_loss	1.0000
6:32167256:CGG:C	donor_loss	1.0000
6:32167256:CGGT:C	donor_loss	1.0000
6:32167257:GGT:G	donor_loss	1.0000
6:32167257:GGTG:G	donor_loss	1.0000
6:32167258:G:GA	donor_loss	1.0000
6:32167259:T:G	donor_loss	1.0000
6:32167341:T:A	acceptor_gain	1.0000
6:32167345:CCTAG:C	acceptor_loss	1.0000
6:32167346:CTAGT:C	acceptor_loss	1.0000
6:32167347:TAGTT:T	acceptor_loss	1.0000
6:32167348:A:AG	acceptor_gain	1.0000
6:32167348:AG:A	acceptor_loss	1.0000
6:32167348:AGTTC:A	acceptor_gain	1.0000
6:32167349:G:A	acceptor_loss	1.0000
6:32167349:G:GA	acceptor_gain	1.0000

AlphaMissense

1887 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32166983:G:C	W136C	0.988
6:32166983:G:T	W136C	0.988
6:32166776:G:C	W100C	0.986
6:32166776:G:T	W100C	0.986
6:32167152:T:C	F166L	0.971
6:32167154:C:A	F166L	0.971
6:32167154:C:G	F166L	0.971
6:32166996:T:A	C141S	0.969
6:32166997:G:C	C141S	0.969
6:32167098:T:A	C148S	0.967
6:32167099:G:C	C148S	0.967
6:32166998:T:G	C141W	0.963
6:32166997:G:A	C141Y	0.959
6:32166963:T:A	C130S	0.953
6:32166964:G:C	C130S	0.953
6:32166969:T:A	C132S	0.952
6:32166970:G:C	C132S	0.952
6:32166762:T:A	C96S	0.947
6:32166763:G:C	C96S	0.947
6:32166724:G:C	R83P	0.946
6:32166996:T:C	C141R	0.943
6:32166997:G:T	C141F	0.943
6:32167119:T:A	C155S	0.943
6:32167120:G:C	C155S	0.943
6:32166589:T:A	C65S	0.941
6:32166590:G:C	C65S	0.941
6:32167138:A:T	N161I	0.939
6:32166610:A:C	S72R	0.937
6:32166612:C:A	S72R	0.937
6:32166612:C:G	S72R	0.937

dbSNP variants (sampled 300 via entrez): RS1000918959 (6:32163153 C>A), RS1001325703 (6:32168680 G>C), RS1002422716 (6:32162700 G>A), RS1002696895 (6:32165807 A>C,G), RS1002765797 (6:32165221 T>G), RS1003002770 (6:32167309 G>A,C,T), RS1003010990 (6:32167430 G>A,C,T), RS1003700601 (6:32163642 C>G), RS1003774329 (6:32163216 C>T), RS1004037698 (6:32164060 T>C), RS1004676124 (6:32163143 C>T), RS1009054759 (6:32165786 CA>C), RS1010253704 (6:32168036 C>T), RS1010284977 (6:32167604 G>A,T), RS1010773218 (6:32166758 A>C,G)

Disease associations

OMIM: gene MIM:609897 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000984_15	Idiopathic membranous nephropathy	1.000000e-41
GCST001834_3	Oleic acid (18:1n-9) levels	1.000000e-06
GCST001942_21	Prostate cancer	5.000000e-09
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_226	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_276	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST007323_23	Risk-taking tendency (4-domain principal component model)	1.000000e-08
GCST008916_27	Asthma	5.000000e-31

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression	2
CGP 52608	affects binding, increases reaction	1
licochalcone B	decreases expression	1
Sunitinib	increases expression	1
Panobinostat	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Etoposide	affects response to substance	1
Polychlorinated Biphenyls	affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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