ELN

elastin

Basic information

Region (hg38): 7:74027789-74069907

Links

ENSG00000049540 ∙ NCBI:2006 ∙ OMIM:130160 ∙ HGNC:3327 ∙ Uniprot:P15502 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• supravalvular aortic stenosis (Definitive), mode of inheritance: AD
• cutis laxa, autosomal dominant 1 (Strong), mode of inheritance: AD
• cutis laxa, autosomal dominant 1 (Strong), mode of inheritance: AD
• cutis laxa, autosomal dominant 1 (Strong), mode of inheritance: AD
• supravalvular aortic stenosis (Definitive), mode of inheritance: AD
• cutis laxa, autosomal dominant 1 (Definitive), mode of inheritance: AD
• supravalvular aortic stenosis (Supportive), mode of inheritance: AD
• autosomal dominant cutis laxa (Supportive), mode of inheritance: AD
• cutis laxa, autosomal dominant 1 (Strong), mode of inheritance: AD
• supravalvular aortic stenosis (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cutis laxa, autosomal dominant 1; Supravalvular aortic stenosis	AD	Cardiovascular	In Cutis laxa, cardiovascular anomalies (eg, aortic aneuryms and pulmonary artery stenosis) are frequent, and surveillance to allow efficient detection and treatment/precautionary measures may be beneficial; In supravalvular aortic stenosis, there is a wide range of severity, including sudden infant death, and early diagnosis and treatment (eg, with surgery in some individuals) may reduce morbidity and mortality	Cardiovascular; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary	5046633; 8475063; 8362925; 8364568; 8091333; 8132745; 8541862; 9215670; 9215671; 9873040; 11175284; 15955094; 16085695; 18348261; 19844261
Individuals with Cutis Laxa may have a clinically recognizable phenotype,

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ELN gene.

• Supravalvar aortic stenosis (82 variants)
• not provided (25 variants)
• ELN-related disorder (4 variants)
• Cutis laxa, autosomal dominant 1 (3 variants)
• Inborn genetic diseases (1 variants)
• Williams syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ELN gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	4	120	5	130
missense	3	2	237	13	5	260
nonsense	19	5				24
start loss	1	1				2
frameshift	63	14				77
inframe indel			28	2		30
splice donor/acceptor (+/-2bp)	12	25	9			46
splice region	1		31	38	4	74
non coding		2	56	124	43	225
Total	98	50	334	259	53

Variants in ELN

This is a list of pathogenic ClinVar variants found in the ELN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-74028118-G-C		Supravalvar aortic stenosis • Cutis laxa, autosomal dominant • Supravalvar aortic stenosis;Williams syndrome;Cutis laxa, autosomal dominant 1	Uncertain significance (Oct 08, 2021)
7-74028150-C-T		Supravalvar aortic stenosis • Cutis laxa, autosomal dominant	Benign (Jun 14, 2016)
7-74028151-G-C		not specified	Likely benign (Mar 27, 2017)
7-74028185-G-A		not specified	Uncertain significance (Apr 26, 2024)
7-74028188-A-G		Supravalvar aortic stenosis	Pathogenic (Oct 05, 2023)
7-74028189-T-C		Supravalvar aortic stenosis	Pathogenic/Likely pathogenic (Feb 12, 2024)
7-74028192-C-T		Supravalvar aortic stenosis	Uncertain significance (Jan 24, 2024)
7-74028192-CG-C		Supravalvar aortic stenosis	Pathogenic (Jul 30, 2020)
7-74028193-G-A		Supravalvar aortic stenosis	Likely benign (May 17, 2021)
7-74028193-G-C		Supravalvar aortic stenosis	Likely benign (Mar 11, 2022)
7-74028195-G-A		Supravalvar aortic stenosis	Uncertain significance (Sep 18, 2023)
7-74028201-C-G		Supravalvar aortic stenosis	Uncertain significance (Dec 04, 2022)
7-74028202-G-A		Supravalvar aortic stenosis • ELN-related disorder	Likely benign (Nov 03, 2022)
7-74028204-C-T		ELN-related disorder	Uncertain significance (Jul 15, 2024)
7-74028205-G-A		Supravalvar aortic stenosis • ELN-related disorder	Likely benign (Oct 05, 2023)
7-74028205-G-C		Supravalvar aortic stenosis	Likely benign (Jan 29, 2024)
7-74028207-C-T		Supravalvar aortic stenosis • Inborn genetic diseases	Uncertain significance (Jul 17, 2024)
7-74028213-C-T		Supravalvar aortic stenosis	Uncertain significance (Jul 17, 2023)
7-74028214-G-A		ELN-related disorder	Likely benign (Nov 26, 2019)
7-74028215-C-T			Uncertain significance (Oct 06, 2022)
7-74028220-C-T		Supravalvar aortic stenosis	Likely benign (Mar 17, 2023)
7-74028221-G-A		not specified • Supravalvar aortic stenosis	Uncertain significance (Jan 04, 2024)
7-74028222-G-T		Cutis laxa, autosomal dominant 1 • Supravalvar aortic stenosis • Cutis laxa, autosomal dominant 1;Williams syndrome;Supravalvar aortic stenosis	Conflicting classifications of pathogenicity (Dec 26, 2023)
7-74028224-G-A		ELN-related disorder	Uncertain significance (Mar 26, 2024)
7-74028228-T-TC		Supravalvar aortic stenosis	Pathogenic (Mar 02, 2012)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ELN	protein_coding	protein_coding	ENST00000252034	33	42119

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.14e-14	0.947	125665	0	83	125748	0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0484	427	430	0.993	0.0000269	4287
Missense in Polyphen
Synonymous	-0.947	194	178	1.09	0.0000138	1813
Loss of Function	2.26	29	45.4	0.639	0.00000223	538

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000559	0.000558
Ashkenazi Jewish	0.00	0.00
East Asian	0.000652	0.000653
Finnish	0.000878	0.000878
European (Non-Finnish)	0.000264	0.000264
Middle Eastern	0.000652	0.000653
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial structure by regulating proliferation and organization of vascular smooth muscle (By similarity). {ECO:0000250|UniProtKB:P54320}.
• Disease: DISEASE: Cutis laxa, autosomal dominant, 1 (ADCL1) [MIM:123700]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. Additional variable clinical features are gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema. {ECO:0000269|PubMed:9873040}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Supravalvular aortic stenosis (SVAS) [MIM:185500]: Congenital narrowing of the ascending aorta which can occur sporadically, as an autosomal dominant condition, or as one component of Williams-Beuren syndrome. {ECO:0000269|PubMed:10942104}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=ELN is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of ELN may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease (PubMed:8812460). {ECO:0000269|PubMed:8812460}.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Lung fibrosis;Integrin (Consensus)

Intolerance Scores

• loftool: 0.815
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.2

Haploinsufficiency Scores

• pHI: 0.931
• hipred: N
• hipred_score: 0.366
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.750

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Eln
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; skeleton phenotype

Gene ontology

• Biological process: outflow tract morphogenesis;aortic valve morphogenesis;respiratory gaseous exchange;blood circulation;cell population proliferation;animal organ morphogenesis;extracellular matrix organization
• Cellular component: extracellular region;extracellular matrix;collagen-containing extracellular matrix;elastic fiber
• Molecular function: extracellular matrix structural constituent;protein binding;extracellular matrix constituent conferring elasticity