ELN
Chr 7ADelastin
Also known as: ADCL1, SVAS, WBS, WS
This gene encodes a protein that is one of the two components of elastic fibers. Elastic fibers comprise part of the extracellular matrix and confer elasticity to organs and tissues including the heart, skin, lungs, ligaments, and blood vessels. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues. Degradation products of the encoded protein, known as elastin-derived peptides or elastokines, bind the elastin receptor complex and other receptors and stimulate migration and proliferation of monocytes and skin fibroblasts. Elastokines can also contribute to cancer progression. Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. [provided by RefSeq, Aug 2017]
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
References
ClinVar Variant Classifications
1341 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 120 | 5 | 22 | 0 | 147 |
Likely Pathogenic | 66 | 5 | 3 | 0 | 74 |
VUS | 18 | 407 | 88 | 15 | 528 |
Likely Benign | 1 | 26 | 204 | 204 | 435 |
Benign | 0 | 2 | 50 | 5 | 57 |
Conflicting | — | 75 | |||
| Total | 205 | 445 | 367 | 224 | 1,316 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →169 pathogenic / likely-pathogenic (of 177) ClinVar copy-number / structural variants overlap ELN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
ELN · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Sulfasalazine in AML Treated by Intensive Chemotherapy: Elderly Patients-first Line Treatment
RECRUITINGCharacterization of the Natural History of Microduplication Syndrome 7q11.23
NOT YET RECRUITINGReal-world Study of Scemblix in the Treatment of Chronic Myeloid Leukemia in China
RECRUITINGEntrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia
ACTIVE NOT RECRUITINGToxicity Genetic Determinants and Response to Azacitidine and Venetoclax in AML
RECRUITINGAsciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase
RECRUITINGComparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)
RECRUITINGA Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML
RECRUITINGCardiovascular Structure and Function in the Mucopolysaccharidoses
ACTIVE NOT RECRUITINGChimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant
RECRUITINGTalazoparib for Cohesin-Mutated AML and MDS With Excess Blasts
ACTIVE NOT RECRUITINGA Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools