ECE1

endothelin converting enzyme 1, the group of M13 metallopeptidases

Basic information

Region (hg38): 1:21217247-21345572

Previous symbols: [ "ECE" ]

Links

ENSG00000117298 ∙ NCBI:1889 ∙ OMIM:600423 ∙ HGNC:3146 ∙ Uniprot:P42892 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• essential hypertension, genetic (No Known Disease Relationship), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hirschsprung disease, cardiac defects, and autonomic dysfunction	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Genitourinary; Musculoskeletal; Neurologic	9915973

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ECE1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ECE1 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				10	5	15
missense		1	36	4	3	44
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	4	6
non coding				4	2	6
Total	0	1	36	18	10

Variants in ECE1

This is a list of pathogenic ClinVar variants found in the ECE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-21217735-G-A			Likely benign (Mar 01, 2023)
1-21217754-T-A			Benign (Feb 01, 2024)
1-21220008-G-A		Hirschsprung disease, cardiac defects, and autonomic dysfunction	Pathogenic (Jan 01, 1999)
1-21220081-G-A			Likely benign (Jun 26, 2018)
1-21220104-T-C		not specified	Uncertain significance (Oct 06, 2021)
1-21220115-C-T		not specified	Uncertain significance (Dec 19, 2023)
1-21225271-C-A		ECE1-related disorder	Likely benign (Jun 13, 2023)
1-21225324-C-T		Hirschsprung disease, cardiac defects, and autonomic dysfunction	Likely pathogenic (Mar 06, 2021)
1-21225330-C-T			Likely benign (Dec 07, 2019)
1-21225337-G-T		not specified	Uncertain significance (Jun 04, 2024)
1-21225379-G-C			Likely benign (Jun 06, 2018)
1-21225387-C-T		not specified	Uncertain significance (Jun 10, 2024)
1-21225406-T-G			Likely benign (Dec 31, 2019)
1-21225411-G-A		Aganglionic megacolon	Likely pathogenic (-)
1-21225424-C-T			Likely benign (Jul 31, 2018)
1-21225426-T-G		not specified	Uncertain significance (Aug 04, 2021)
1-21225437-C-T		ECE1-related disorder	Uncertain significance (Jan 05, 2024)
1-21227230-G-T		not specified	Benign (-)
1-21227959-C-G		not specified	Uncertain significance (Dec 07, 2021)
1-21227971-C-T		not specified	Uncertain significance (Dec 27, 2023)
1-21228002-C-T			Benign (Dec 31, 2019)
1-21228026-C-T			Likely benign (Feb 08, 2018)
1-21228061-AG-CC		not specified	Likely benign (-)
1-21233559-G-C		not specified	Uncertain significance (Jan 23, 2024)
1-21233567-T-C		not specified	Uncertain significance (Jun 03, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ECE1	protein_coding	protein_coding	ENST00000374893	19	128258

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.960	0.0401	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.31	315	453	0.695	0.0000294	5060
Missense in Polyphen		96	196.1	0.48956		2250
Synonymous	0.0901	186	188	0.992	0.0000137	1445
Loss of Function	4.91	7	40.9	0.171	0.00000198	480

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000704	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts big endothelin-1 to endothelin-1. {ECO:0000269|PubMed:9396733}.
• Pathway: Endothelin Pathways;Corticotropin-releasing hormone signaling pathway;Melatonin metabolism and effects;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);CRH;GPCR ligand binding (Consensus)

Recessive Scores

• pRec: 0.390

Intolerance Scores

• loftool: 0.0216
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.32

Haploinsufficiency Scores

• pHI: 0.316
• hipred: Y
• hipred_score: 0.728
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.531

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ece1
• Phenotype: muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; 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); normal phenotype; hematopoietic system 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)

Zebrafish Information Network

• Gene name: ece1
• Affected structure: ceratobranchial cartilage
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: positive regulation of receptor recycling;regulation of systemic arterial blood pressure by endothelin;heart development;substance P catabolic process;bradykinin catabolic process;calcitonin catabolic process;protein processing;peptide hormone processing;regulation of vasoconstriction;endothelin maturation;hormone catabolic process;embryonic digit morphogenesis;ear development;pharyngeal system development
• Cellular component: lysosomal membrane;endosome;plasma membrane;external side of plasma membrane;membrane;integral component of membrane;intrinsic component of endosome membrane;vesicle;Weibel-Palade body;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: endopeptidase activity;metalloendopeptidase activity;protein binding;zinc ion binding;peptide hormone binding;protein homodimerization activity