ECEL1

protein-coding

endothelin converting enzyme like 1, the group of M13 metallopeptidases

Gene summary

This gene encodes a member of the M13 family of endopeptidases. Members of this family are zinc-containing type II integral-membrane proteins that are important regulators of neuropeptide and peptide hormone activity. Mutations in this gene are associated with autosomal recessive distal arthrogryposis, type 5D. This gene has multiple pseudogenes on chromosome 2. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

MANE transcript

NM_004826.4

Inheritance

ClinVar variants

P:71U:134B:59

Top phenotype

Arthrogryposis, distal, type 5D

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr2:232,479,827-232,487,834

External References & Databases

Ensembl (ENSG00000171551)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

distal arthrogryposis type 5DSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014028

Submitter: Orphanet

distal arthrogryposis type 5DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014028

Submitter: Labcorp Genetics (formerly Invitae)

distal arthrogryposis type 5DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014028

Submitter: PanelApp Australia

distal arthrogryposis type 5DDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014028

Submitter: G2P

distal arthrogryposis type 5DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014028

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Arthrogryposis, distal, type 5DAR

Manifestation: Craniofacial; Musculoskeletal

Intervention: General

Rationale: 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

Refs: 23236030; 23261301; 25099528

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ECEL1 variants in ClinVar

10 Conditions Cataloged

Inborn genetic diseasesTotal: 110

not providedTotal: 98

Distal arthrogryposis type 5DTotal: 85

ECEL1-related disorderTotal: 32

not specifiedTotal: 30

ECEL1-related disordersTotal: 8

See casesTotal: 3

Distal arthrogryposisTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004826.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	2 clinvar	36 clinvar	4 clinvar	43
missense	4 clinvar	19 clinvar	131 clinvar	18 clinvar	1 clinvar	173
nonsense	9 clinvar	9 clinvar				18
start loss		1 clinvar				1
frameshift	9 clinvar	5 clinvar				14
splice donor/acceptor (+/-2bp)	8 clinvar	6 clinvar	1 clinvar			15
Total	30	41	134	54	5	264

Highest pathogenic variant AF is 0.0000929716

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004826.4	RefSeq	NP_004817.2	17	MANE Select
ENST00000304546.6	Ensembl	ENSP00000302051.1	17	MANE Select
NM_001290787.2	RefSeq	NP_001277716.1	17	Standard
ENST00000409941.1	Ensembl	ENSP00000386333.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

respiratory system process
proteolysis
neuropeptide signaling pathway

Molecular Function

metalloendopeptidase activity
metallopeptidase activity
metal ion binding

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304546
Coding exons: 17
Length: 8002
Individuals with no LoFs: 125687
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 125747
p: 0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.478	409	437	0.936	0.0000256	4917
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00023	0.00023	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.362

Gene Damage Prediction

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