ECEL1

endothelin converting enzyme like 1, the group of M13 metallopeptidases

Basic information

Region (hg38): 2:232479827-232487834

Links

ENSG00000171551 ∙ NCBI:9427 ∙ OMIM:605896 ∙ HGNC:3147 ∙ Uniprot:O95672 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• distal arthrogryposis type 5D (Definitive), mode of inheritance: AR
• distal arthrogryposis type 5D (Strong), mode of inheritance: AR
• distal arthrogryposis type 5D (Strong), mode of inheritance: AR
• distal arthrogryposis type 5D (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis, distal, type 5D	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	23236030; 23261301; 25099528

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ECEL1 gene.

• Distal arthrogryposis type 5D (16 variants)
• not provided (8 variants)
• See cases (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ECEL1 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	25	3	29
missense	2	7	58	9	3	79
nonsense	6	2				8
start loss						0
frameshift	7	3				10
inframe indel						0
splice donor/acceptor (+/-2bp)	6	1				7
splice region		1	1	4	1	7
non coding				12	22	34
Total	21	13	59	46	28

Highest pathogenic variant AF is 0.000138

Variants in ECEL1

This is a list of pathogenic ClinVar variants found in the ECEL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-232480018-G-C			Benign (Nov 11, 2018)
2-232480086-T-A			Likely benign (Nov 14, 2019)
2-232480161-C-T		Inborn genetic diseases • Distal arthrogryposis type 5D	Uncertain significance (May 06, 2024)
2-232480167-A-G		Distal arthrogryposis type 5D	Uncertain significance (Mar 12, 2024)
2-232480170-T-C		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
2-232480184-A-G		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
2-232480192-G-C		Inborn genetic diseases	Uncertain significance (May 20, 2024)
2-232480202-C-A		Distal arthrogryposis type 5D	Uncertain significance (Jul 12, 2019)
2-232480203-A-G		Distal arthrogryposis type 5D	Pathogenic (Apr 15, 2013)
2-232480205-T-G			Uncertain significance (May 08, 2023)
2-232480215-G-A		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
2-232480239-C-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
2-232480259-T-G		not specified	Conflicting classifications of pathogenicity (Mar 29, 2018)
2-232480281-T-G		Distal arthrogryposis type 5D	Benign (Jul 30, 2021)
2-232480395-A-T		ECEL1-related disorder	Likely benign (May 06, 2019)
2-232480399-C-A		Arthrogryposis multiplex congenita	Uncertain significance (Apr 09, 2019)
2-232480401-G-A			Likely benign (Jun 13, 2018)
2-232480429-A-G		ECEL1-related disorder	Uncertain significance (Jul 17, 2023)
2-232480452-C-T			Benign (Dec 31, 2019)
2-232480456-C-T		Inborn genetic diseases	Uncertain significance (Aug 10, 2021)
2-232480461-C-T		ECEL1-related disorder	Likely benign (Dec 31, 2019)
2-232480539-C-A			Benign (Oct 02, 2019)
2-232480539-C-T			Benign (Nov 11, 2018)
2-232480716-A-G		Distal arthrogryposis type 5D	Likely pathogenic (May 04, 2020)
2-232480716-A-T		Distal arthrogryposis type 5D	Pathogenic (Nov 16, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ECEL1	protein_coding	protein_coding	ENST00000304546	17	8002

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.79e-13	0.984	125687	0	60	125747	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.478	409	437	0.936	0.0000256	4917
Missense in Polyphen		137	161.04	0.85072		1884
Synonymous	-0.324	197	191	1.03	0.0000116	1538
Loss of Function	2.46	27	44.8	0.603	0.00000256	444

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00150	0.00150
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000178	0.000176
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May contribute to the degradation of peptide hormones and be involved in the inactivation of neuronal peptides.
• Disease: DISEASE: Arthrogryposis, distal, 5D (DA5D) [MIM:615065]: An autosomal recessive form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA5D is characterized by severe camptodactyly of the hands, mild camptodactyly of the toes, clubfoot and/or a calcaneovalgus deformity, extension contractures of the knee, unilateral ptosis or ptosis that is more severe on one side, a round-shaped face, arched eyebrows, a bulbous upturned nose, and micrognathia. Patients do not have ophthalmoplegia. {ECO:0000269|PubMed:23236030, ECO:0000269|PubMed:23261301, ECO:0000269|PubMed:23808592, ECO:0000269|PubMed:23829171}. Note=The disease is caused by mutations affecting the gene represented in this entry. ECEL1 mutations have also been found in patients with arthrogryposis, significant ophthalmoplegia, and refractive errors (PubMed:23808592). {ECO:0000269|PubMed:23808592}.

Recessive Scores

• pRec: 0.205

Intolerance Scores

• loftool: 0.207
• rvis_EVS: 0
• rvis_percentile_EVS: 54.07

Haploinsufficiency Scores

• pHI: 0.130
• hipred: Y
• hipred_score: 0.782
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.362

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ecel1
• 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); respiratory system 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); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: respiratory system process;proteolysis;neuropeptide signaling pathway
• Cellular component: integral component of plasma membrane
• Molecular function: metalloendopeptidase activity;metallopeptidase activity;metal ion binding