EMILIN1

Summary

EMILIN1 (elastin microfibril interfacer 1, HGNC:19880) is a protein-coding gene on chromosome 2p23.3, encoding EMILIN-1 (Q9Y6C2). Involved in elastic and collagen fibers formation.

This gene encodes an extracellular matrix glycoprotein that is characterized by an N-terminal microfibril interface domain, a coiled-coiled alpha-helical domain, a collagenous domain and a C-terminal globular C1q domain. The encoded protein associates with elastic fibers at the interface between elastin and microfibrils and may play a role in the development of elastic tissues including large blood vessels, dermis, heart and lung.

Source: NCBI Gene 11117 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arterial tortuosity-bone fragility syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 239 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 132
• MANE Select transcript: NM_007046

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19880
Approved symbol	EMILIN1
Name	elastin microfibril interfacer 1
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp586M121, gp115, EMILIN
Ensembl gene	ENSG00000138080
Ensembl biotype	protein_coding
OMIM	130660
Entrez	11117

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 16 protein_coding

ENST00000380320, ENST00000433140, ENST00000865593, ENST00000865594, ENST00000865595, ENST00000865596, ENST00000865597, ENST00000957369, ENST00000957370, ENST00000957371, ENST00000957372, ENST00000957373, ENST00000957374, ENST00000957375, ENST00000957376, ENST00000957377

RefSeq mRNA: 1 — MANE Select: NM_007046 NM_007046

CCDS: CCDS1733

Canonical transcript exons

ENST00000380320 — 8 exons

Exon	Start	End
ENSE00000732220	27080151	27080270
ENSE00000732221	27080732	27080952
ENSE00000732225	27084415	27084531
ENSE00000809129	27082083	27084011
ENSE00000809130	27085160	27085297
ENSE00001484569	27078615	27079235
ENSE00001669474	27085678	27086403
ENSE00001802271	27084991	27085008

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.5045 / max 1920.9543, expressed in 1119 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19315	28.1497	1092
19316	15.1115	1009
19317	6.2433	809

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	98.70	gold quality
body of uterus	UBERON:0009853	98.47	gold quality
left uterine tube	UBERON:0001303	98.42	gold quality
right ovary	UBERON:0002118	98.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.25	gold quality
ascending aorta	UBERON:0001496	98.21	gold quality
thoracic aorta	UBERON:0001515	98.20	gold quality
descending thoracic aorta	UBERON:0002345	98.11	gold quality
left ovary	UBERON:0002119	97.93	gold quality
left coronary artery	UBERON:0001626	97.89	gold quality
stromal cell of endometrium	CL:0002255	97.83	gold quality
coronary artery	UBERON:0001621	97.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.22	gold quality
lower esophagus	UBERON:0013473	97.20	gold quality
aorta	UBERON:0000947	97.07	gold quality
endocervix	UBERON:0000458	96.62	gold quality
popliteal artery	UBERON:0002250	96.31	gold quality
tibial artery	UBERON:0007610	96.30	gold quality
metanephros cortex	UBERON:0010533	96.18	gold quality
mucosa of stomach	UBERON:0001199	95.96	gold quality
upper lobe of left lung	UBERON:0008952	95.74	gold quality
myometrium	UBERON:0001296	95.53	gold quality
spleen	UBERON:0002106	94.99	gold quality
upper lobe of lung	UBERON:0008948	94.89	gold quality
fundus of stomach	UBERON:0001160	93.85	gold quality
apex of heart	UBERON:0002098	93.54	gold quality
left adrenal gland cortex	UBERON:0035825	93.47	gold quality
right adrenal gland	UBERON:0001233	93.42	gold quality
left adrenal gland	UBERON:0001234	93.37	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	100.11
E-HCAD-1	yes	79.68
E-HCAD-10	yes	56.06
E-GEOD-135922	yes	49.78
E-HCAD-11	yes	49.26
E-GEOD-134144	yes	41.25
E-MTAB-8410	yes	39.31
E-CURD-46	yes	22.72
E-CURD-112	yes	13.48
E-ANND-3	yes	12.00
E-MTAB-10553	yes	5.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting EMILIN1, 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-6515-3P	99.82	68.19	1933
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-1238-3P	95.27	62.25	552

Literature-anchored findings (GeneRIF, showing 26)

• beta1 Integrin-dependent cell adhesion to this protein is mediated by its gC1q domain (PMID:12456677)
• NMR assignments for the C-terminal globular domain of EMILIN-1 (PMID:15017143)
• EMILIN1 interacts with anthrax protective antigen and inhibits toxin action in vitro. EMILIN1 may be a potential target and/or a protein useful for countermeasures against B. anthracis toxin lethality. (PMID:17988845)
• EMILIN1 is a novel local regulator of lymphangiogenesis (PMID:18411305)
• EMILIN1 gC1q-alpha4beta1 represents a unique ligand/receptor system, with a requirement for a 3-fold arrangement of the interaction site. (PMID:18463100)
• Our findings don’t support positive association of Emilin1 gene with EH, but the interaction of age and genotype variation of rs3754734 and rs2011616 might increase the risk to hypertension (PMID:19922630)
• rs2289360, rs2011616, and rs2304682 in the human EMILIN1 gene, as well as the haplotype constructed using rs2536512, rs2011616, and rs17881426, are useful genetic markers of essential hypertension in Japanese men. (PMID:20186130)
• EMILIN-1 may regulate the formation of oxytalan fibers and play a role in their homeostasis. (PMID:20701466)
• All three SNPs in introns 1 and 5 (rs2289360, rs2011616 and rs7424556) of EMILIN1 were in strong pair-wise linkage disequilibrium and were significantly associated with hypertension. (PMID:21753788)
• There were significant associations of rs2011616 and rs2304682 polymorphisms in the EMILIN1 gene with hypertension among Japanese. (PMID:22639547)
• Emilin-1 produced by vascular smooth muscle cells acts as a main regulator of resting blood pressure levels by controlling the myogenic response in resistance arteries through TGF-beta. (PMID:22814752)
• The present findings highlight the peculiar activity of PMN elastase in disabling EMILIN1 suppressor function. (PMID:24513040)
• Data suggested mechanisms for homo- and hetero-typic EMILINs multimers formation: EMILIN1 or EMILIN2 alone can form trimers and multimers in the absence of each other or they can co-polymerize in a head-to-tail fashion to form hetero-typic multimers. (PMID:25445627)
• These findings collectively suggest that EMILIN1 may represent a new disease gene associated with an autosomal-dominant connective tissue disorder. (PMID:26462740)
• This study is the first to identify EMILIN-1 and ILK as prospective markers of islet regenerative function in human mesenchymal stem cells. (PMID:27090767)
• Study discloses a novel mechanism of interaction occurring between the trimeric gC1q domain of EMILIN1 and the alpha4beta1 integrin and determines that the three E933 residues (one from each monomer) are all required for ligand binding. Furthermore, R904 was identified as a synergistic residue for cell adhesion. (PMID:29037761)
• Report reduced EMILIN-1 and enhanced myogenic tone, dependent on increased TGF-beta-EGFR signaling, in resistance arteries from hypertensive patients. (PMID:30354220)
• Data provide evidence that the novel “regulatory structural” role of EMILIN-1 in the lymphangiogenic process is played by the integrin binding site within its gC1q domain. (PMID:30408617)
• EMILIN1 induces anti-tumor effects by up-regulating TSPAN9 expression in gastric cancer. Hence, membrane proteins TSPAN9 and EMILIN1 may represent novel therapeutic targets for the treatment of gastric cancer. (PMID:31242895)
• Elastin MIcrofibriL INterfacer1 (EMILIN-1) is an alternative prosurvival VLA-4 ligand in chronic lymphocytic leukemia. (PMID:34783040)
• EMILIN-1 deficiency promotes chronic inflammatory disease through TGFbeta signaling alteration and impairment of the gC1q/alpha4beta1 integrin interaction. (PMID:35764213)
• EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis. (PMID:36351433)
• The role of EMILIN-1 in the osteo/odontogenic differentiation of dental pulp stem cells. (PMID:37024847)
• Integrated machine learning-driven disulfidptosis profiling: CYFIP1 and EMILIN1 as therapeutic nodes in neuroblastoma. (PMID:38427078)
• Cancer-associated fibroblast spatial heterogeneity and EMILIN1 expression in the tumor microenvironment modulate TGF-beta activity and CD8[+] T-cell infiltration in breast cancer. (PMID:38505604)
• The extracellular matrix protein EMILIN-1 impacts on the microenvironment by hampering gastric cancer development and progression. (PMID:38941035)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	emilin1a	ENSDARG00000024537
danio_rerio	emilin1b	ENSDARG00000026166
mus_musculus	Emilin1	ENSMUSG00000029163
rattus_norvegicus	Emilin1	ENSRNOG00000008246

Paralogs (4): EMILIN2 (ENSG00000132205), MMRN1 (ENSG00000138722), MMRN2 (ENSG00000173269), EMILIN3 (ENSG00000183798)

Protein

Protein identifiers

EMILIN-1 — Q9Y6C2 (reviewed: Q9Y6C2)

Alternative names: Elastin microfibril interface-located protein 1

All UniProt accessions (2): Q9Y6C2, A0A0A0MT20

UniProt curated annotations — full annotation on UniProt →

Function. Involved in elastic and collagen fibers formation. It is required for EFEMP2 deposition into the extracellular matrix, and collagen network assembly and cross-linking via protein-lysine 6-oxidase/LOX activity. May be responsible for anchoring smooth muscle cells to elastic fibers, and may be involved in the processes that regulate vessel assembly. Has cell adhesive capacity.

Subunit / interactions. Homotrimer associated through a moderately stable interaction of the C-terminal globular C1q domains, allowing the nucleation of the triple helix and then a further quaternary assembly to higher-order polymers via intermolecular disulfide bonds. Interacts with EMILIN2. Interacts with EFEMP2; this interaction promotes the incorporation of EFEMP2 into the extracellular matrix.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Distributed in tissues where resilience and elastic recoil are prominent. Highest levels in the adult small intestine, aorta, lung, uterus, and appendix and in the fetal spleen, kidney, lung, and heart; intermediate expression was detected in adult liver, ovary, colon, stomach, lymph node and spleen; adult heart, bladder, prostate, adrenal gland, mammary gland, placenta and kidney showed low expression whereas a series of other adult tissues, including skeletal muscle and different regions of adult brain show no expression. Detected in intramuscular nerve bundles, where it particularly localizes in the epineurium, the most external layer of dense connective tissue enclosing the nerve.

Disease relevance. Neuronopathy, distal hereditary motor, autosomal dominant 10 (HMND10) [MIM:620080] A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. HMND10 is characterized by length-dependent motor neuropathy primarily affecting the lower limbs, and onset of distal muscle weakness and atrophy in early childhood resulting in walking difficulties and gait abnormalities. Some affected individuals have pyramidal signs, including hyperreflexia. More variable features may include mild intellectual disability, minor gyration defects on brain imaging, foot deformities, and connective tissue defects. The disease is caused by variants affecting the gene represented in this entry. Arterial tortuosity-bone fragility syndrome (ATBFS) [MIM:620908] An autosomal recessive disorder characterized by congenital arterial tortuosity, mainly affecting the aorta and main aortic side branches, aneurysm of the aortic root, and bone fragility resulting in fractures of the ribs, clavicle, acromion, metatarsal, or long bones. Tortuosity of the retinal arteries is present in some patients. Connective tissue features include blue sclerae, mild cutis laxa with a thin and velvety skin, joint hyperlaxity, and arachnodactyly. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Its deposition precedes the appearance of elastin and is simultaneous with that of fibrillin 1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6C2-1	1	yes
Q9Y6C2-2	2

RefSeq proteins (1): NP_008977* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR011489	EMI_domain	Domain
IPR050392	Collagen/C1q_domain	Family

Pfam: PF00386, PF01391, PF07546

UniProt features (51 total): strand 10, glycosylation site 7, region of interest 6, sequence variant 6, coiled-coil region 5, compositionally biased region 4, domain 3, disulfide bond 3, splice variant 3, turn 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2KA3	SOLUTION NMR
2OII	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6C2-F1	63.73	0.06

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 (3): 60–121, 85–92, 120–129

Glycosylation sites (7): 154, 415, 455, 561, 658, 766, 794

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2129379	Molecules associated with elastic fibres

MSigDB gene sets: 565 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_COAGULATION, GOCC_COLLAGEN_TRIMER, LFA1_Q6, GOBP_PLATELET_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT

GO Biological Process (29): aortic valve morphogenesis (GO:0003180), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), regulation of blood pressure (GO:0008217), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of cell-substrate adhesion (GO:0010811), cell migration (GO:0016477), negative regulation of angiogenesis (GO:0016525), positive regulation of blood coagulation (GO:0030194), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030948), negative regulation of collagen biosynthetic process (GO:0032966), cell adhesion mediated by integrin (GO:0033627), regulation of cell population proliferation (GO:0042127), positive regulation of apoptotic process (GO:0043065), positive regulation of angiogenesis (GO:0045766), elastic fiber assembly (GO:0048251), negative regulation of cell activation (GO:0050866), negative regulation of SMAD protein signal transduction (GO:0060392), negative regulation of ERK1 and ERK2 cascade (GO:0070373), positive regulation of defense response to bacterium (GO:1900426), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747), positive regulation of extracellular matrix assembly (GO:1901203), positive regulation of platelet aggregation (GO:1901731), negative regulation of collagen fibril organization (GO:1904027), negative regulation of macrophage migration (GO:1905522), extracellular matrix organization (GO:0030198)

GO Molecular Function (6): extracellular matrix constituent conferring elasticity (GO:0030023), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), integrin binding involved in cell-matrix adhesion (GO:0098640), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), integrin alpha4-beta1 complex (GO:0034668), extracellular exosome (GO:0070062), EMILIN complex (GO:1990971)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Elastic fibre formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-substrate adhesion	2
gene expression	2
regulation of gene expression	2
angiogenesis	2
regulation of angiogenesis	2
binding	2
aortic valve development	1
heart valve morphogenesis	1
cellular process	1
blood circulation	1
regulation of biological quality	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of cell-substrate adhesion	1
positive regulation of cell adhesion	1
cell motility	1
negative regulation of blood vessel morphogenesis	1
blood coagulation	1
regulation of blood coagulation	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
negative regulation of biosynthetic process	1
negative regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
cell adhesion	1
cell population proliferation	1
regulation of cellular process	1
apoptotic process	1

Protein interactions and networks

STRING

1002 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMILIN1	ELN	P15502	865
EMILIN1	KHK	P50053	715
EMILIN1	TYRP1	P17643	556
EMILIN1	FN1	P02751	490
EMILIN1	FURIN	P09958	465
EMILIN1	ITGA4	P13612	439
EMILIN1	DCN	P07585	436
EMILIN1	CNBP	P20694	422
EMILIN1	FBN1	P35555	406
EMILIN1	CEACAM8	P31997	396
EMILIN1	ICAM1	P05362	389
EMILIN1	LTBP2	Q14767	377
EMILIN1	TIMP1	P01033	376
EMILIN1	CASP3	P42574	375
EMILIN1	MMP3	P08254	367

IntAct

90 interactions, top by confidence:

A	B	Type	Score
EMILIN1	MTMR9	psi-mi:“MI:0915”(physical association)	0.880
MTMR9	EMILIN1	psi-mi:“MI:0915”(physical association)	0.880
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
BEX5	EMILIN1	psi-mi:“MI:0915”(physical association)	0.670
EMILIN1	LAIR2	psi-mi:“MI:0915”(physical association)	0.670
EMILIN1	NMI	psi-mi:“MI:0915”(physical association)	0.670
TAX1BP1	EMILIN1	psi-mi:“MI:0915”(physical association)	0.670
NMI	EMILIN1	psi-mi:“MI:0915”(physical association)	0.670
EMILIN1	TAX1BP1	psi-mi:“MI:0915”(physical association)	0.670
LAIR2	EMILIN1	psi-mi:“MI:0915”(physical association)	0.670
EMILIN1	BEX5	psi-mi:“MI:0915”(physical association)	0.670
EMILIN1	PLAC9	psi-mi:“MI:0915”(physical association)	0.640

BioGRID (162): EMILIN1 (Two-hybrid), EMILIN1 (Two-hybrid), EMILIN1 (Two-hybrid), EMILIN1 (Two-hybrid), EMILIN1 (Two-hybrid), NGFRAP1 (Two-hybrid), MTMR9 (Two-hybrid), ZC2HC1C (Two-hybrid), IFT20 (Two-hybrid), RIBC1 (Two-hybrid), PLAC9 (Two-hybrid), BEX5 (Two-hybrid), MTMR9 (Two-hybrid), EMILIN1 (Two-hybrid), MTMR9 (Two-hybrid)

ESM2 similar proteins: A4FV93, A4IIA2, A5A8Y8, B2LW77, D3Z7H8, D3ZUK3, D4AB34, O75074, O88204, P07204, P15306, P24592, P35572, P47880, P51693, P60882, Q03157, Q2KJ51, Q32L50, Q3SWY4, Q3TYX2, Q4G0M1, Q501P1, Q53RD9, Q5RKR3, Q5W7P8, Q5XHC5, Q61810, Q6AZ60, Q6GUQ1, Q6MG84, Q6PGN1, Q6UY11, Q71U07, Q7Z7M0, Q86VZ4, Q8CB67, Q8IVN8, Q8K099, Q8K1E3

Diamond homologs: A6H6E2, F1QC17, P59900, Q13201, Q8K482, Q91VF6, Q96A83, Q96A84, Q99K41, Q9BXX0, Q9H8L6, Q9NT22, Q9Y6C2, A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P02747, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P31722, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	192
Likely benign	14
Benign	9

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1343812	NM_007046.4(EMILIN1):c.2457_2482dup (p.Gln828fs)	Pathogenic
1343813	NM_007046.4(EMILIN1):c.1606C>T (p.Gln536Ter)	Pathogenic
1344492	NM_007046.4(EMILIN1):c.119dup (p.Ser40fs)	Pathogenic
1527980	NM_007046.4(EMILIN1):c.831dup (p.Ala278fs)	Pathogenic
1527981	NM_007046.4(EMILIN1):c.151del (p.Arg51fs)	Pathogenic
1711105	NM_007046.4(EMILIN1):c.748C>T (p.Arg250Cys)	Pathogenic
4845901	NM_007046.4(EMILIN1):c.1333C>T (p.Arg445Ter)	Likely pathogenic

SpliceAI

978 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27084529:CAG:C	donor_loss	1.0000
2:27084530:AGG:A	donor_loss	1.0000
2:27084533:T:A	donor_loss	1.0000
2:27085277:GCTAT:G	donor_gain	1.0000
2:27085676:A:AG	acceptor_gain	1.0000
2:27085676:AG:A	acceptor_gain	1.0000
2:27085676:AGGC:A	acceptor_gain	1.0000
2:27085677:G:GT	acceptor_gain	1.0000
2:27085677:GG:G	acceptor_gain	1.0000
2:27085677:GGC:G	acceptor_gain	1.0000
2:27085677:GGCG:G	acceptor_gain	1.0000
2:27085677:GGCGT:G	acceptor_gain	1.0000
2:27080271:G:GG	donor_gain	0.9900
2:27082077:CCTCA:C	acceptor_loss	0.9900
2:27082078:CTCA:C	acceptor_loss	0.9900
2:27082079:TCA:T	acceptor_loss	0.9900
2:27082080:CA:C	acceptor_loss	0.9900
2:27082082:G:GA	acceptor_loss	0.9900
2:27084410:TGTA:T	acceptor_loss	0.9900
2:27084411:GTA:G	acceptor_loss	0.9900
2:27084412:TA:T	acceptor_loss	0.9900
2:27084413:A:AC	acceptor_loss	0.9900
2:27084414:G:GT	acceptor_loss	0.9900
2:27084497:C:T	donor_gain	0.9900
2:27085159:GGA:G	acceptor_gain	0.9900
2:27079233:CAGG:C	donor_loss	0.9800
2:27079236:G:GA	donor_loss	0.9800
2:27079237:T:G	donor_loss	0.9800
2:27082081:A:AG	acceptor_gain	0.9800
2:27082082:G:GG	acceptor_gain	0.9800

AlphaMissense

6421 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27080795:G:C	W118C	1.000
2:27080795:G:T	W118C	1.000
2:27085684:T:C	F907S	1.000
2:27085202:T:C	F873S	0.999
2:27085250:T:C	F889S	0.999
2:27085250:T:G	F889C	0.999
2:27085707:T:G	Y915D	0.999
2:27085755:G:C	A931P	0.999
2:27080793:T:A	W118R	0.998
2:27080793:T:C	W118R	0.998
2:27085201:T:C	F873L	0.998
2:27085202:T:G	F873C	0.998
2:27085203:T:A	F873L	0.998
2:27085203:T:G	F873L	0.998
2:27085244:T:A	V887D	0.998
2:27085249:T:C	F889L	0.998
2:27085251:C:A	F889L	0.998
2:27085251:C:G	F889L	0.998
2:27085282:T:G	Y900D	0.998
2:27085684:T:G	F907C	0.998
2:27085912:T:A	V983D	0.998
2:27085969:T:C	F1002S	0.998
2:27085249:T:A	F889I	0.997
2:27085678:G:T	G905V	0.997
2:27085762:T:C	L933P	0.997
2:27085918:T:A	V985D	0.997
2:27085924:T:C	L987P	0.997
2:27085971:A:C	S1003R	0.997
2:27085973:C:A	S1003R	0.997
2:27085973:C:G	S1003R	0.997

dbSNP variants (sampled 300 via entrez): RS1000177995 (2:27078560 G>A,C,T), RS1000737897 (2:27077332 G>C), RS1001193203 (2:27078355 T>G), RS1002037121 (2:27077031 C>T), RS1002468313 (2:27086659 C>T), RS1002847759 (2:27086455 C>T), RS1003030976 (2:27081411 C>T), RS1003208841 (2:27084863 T>C), RS1003494024 (2:27081079 G>A,C), RS1004372786 (2:27086670 C>A), RS1004421910 (2:27083632 T>C), RS1004656655 (2:27078328 G>A), RS1005537643 (2:27076664 C>T), RS1005626030 (2:27079318 C>T), RS1005848344 (2:27078051 C>A,T)

Disease associations

OMIM: gene MIM:130660 | disease phenotypes: MIM:619435, MIM:620908, MIM:620080

GenCC curated gene-disease

Disease	Classification	Inheritance
neuronopathy, distal hereditary motor, autosomal dominant 10	Strong	Autosomal dominant
arterial tortuosity-bone fragility syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
arterial tortuosity-bone fragility syndrome	Definitive	AR

Mondo (5): Ritscher-Schinzel syndrome 4 (MONDO:0030331), EMILIN-1-related connective tissue disease (MONDO:0044622), arterial tortuosity-bone fragility syndrome (MONDO:0971179), neuronopathy, distal hereditary motor, autosomal dominant 10 (MONDO:0859300), prostate cancer (MONDO:0008315)

Orphanet (2): EMILIN-1-related connective tissue disease (Orphanet:485418), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

132 total (30 of 132 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000076	Vesicoureteral reflux
HP:0000081	Duplicated collecting system
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000444	Convex nasal ridge
HP:0000455	Broad nasal tip
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000518	Cataract
HP:0000541	Retinal detachment
HP:0000545	Myopia

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST010697_14	Cortical surface area (min-P)	2.000000e-09
GCST010698_75	Subcortical volume (min-P)	2.000000e-13
GCST010699_41	Brain morphology (min-P)	2.000000e-08
GCST010700_38	Cortical thickness (MOSTest)	3.000000e-08
GCST010701_56	Cortical surface area (MOSTest)	4.000000e-16
GCST010702_20	Subcortical volume (MOSTest)	2.000000e-64
GCST010703_76	Brain morphology (MOSTest)	1.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cadmium	increases palmitoylation, decreases expression, decreases reaction, increases abundance	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
deoxynivalenol	decreases expression	1
potassium perchlorate	decreases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Methyl Methanesulfonate	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
beta-Naphthoflavone	increases expression	1
tert-Butylhydroperoxide	affects expression	1
Vitamin K 3	affects expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer