distal arthrogryposis type 5D

Summary

distal arthrogryposis type 5D (MONDO:0014028) is a disease caused by ECEL1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ECEL1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 87

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		33	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	distal arthrogryposis type 5D
Mondo ID	MONDO:0014028
OMIM	615065
Orphanet	329457
DOID	DOID:0111594
UMLS	C3554415
MedGen	767329
GARD	0013059
Is cancer (heuristic)	no

Also known as: arthrogryposis, distal, type 5D · DA5D · distal arthrogryposis caused by mutation in ECEL1 · distal arthrogryposis type 5 without ophthalmoparesis · distal arthrogryposis type 5 without ophthalmoplegia · ECEL1 distal arthrogryposis

Data availability: 87 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › distal arthrogryposis › distal arthrogryposis type 5D

Related subtypes (22): arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome, arthrogryposis-like hand anomaly-sensorineural deafness syndrome, Gordon syndrome, congenital contractural arachnodactyly, arthrogryposis, distal, type 2E, trismus-pseudocamptodactyly syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, Freeman-Sheldon syndrome, Sheldon-hall syndrome, Ehlers-Danlos syndrome, musculocontractural type, arthrogryposis-severe scoliosis syndrome, autism spectrum disorder - epilepsy - arthrogryposis syndrome, arthrogryposis, distal, with impaired proprioception and touch, digitotalar dysmorphism, distal arthrogryposis type 10, distal arthrogryposis Moore weaver type, arthrogryposis, distal, type 1C, arthrogryposis, distal, IIa 11, arthrogryposis-ectodermal dysplasia-other anomalies syndrome, ACTC1-related distal arthrogryposis with congenital heart disease, arthrogryposis, distal, type 2B4, arthrogryposis, distal, type 12

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

87 retrieved; paginated sample, class counts are floors:

28 pathogenic, 25 likely pathogenic, 20 uncertain significance, 7 conflicting classifications of pathogenicity, 4 benign, 2 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
235817	NM_004826.3(ECEL1):c.[1252C>T;590G>A]		Pathogenic	criteria provided, single submitter
235818	NM_004826.3(ECEL1):c.[1184+3A>T;1252C>A]		Pathogenic	criteria provided, single submitter
235821	NM_004826.3(ECEL1):c.[344_355delACCTGGACGCCA;716dupA]		Pathogenic	criteria provided, single submitter
100650	NM_004826.4(ECEL1):c.2278T>C (p.Cys760Arg)	ECEL1	Pathogenic	no assertion criteria provided
100651	NM_004826.4(ECEL1):c.1649C>G (p.Ser550Ter)	ECEL1	Pathogenic	no assertion criteria provided
100652	NM_004826.4(ECEL1):c.1685+1G>T	ECEL1	Pathogenic	no assertion criteria provided
1048794	NM_004826.4(ECEL1):c.2151+1G>T	ECEL1	Pathogenic	criteria provided, single submitter
161451	NM_004826.4(ECEL1):c.2023G>A (p.Ala675Thr)	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
1687243	NM_004826.4(ECEL1):c.80del (p.Gly27fs)	ECEL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706601	NM_004826.4(ECEL1):c.1672del (p.Val558fs)	ECEL1	Pathogenic	criteria provided, single submitter
1803196	NM_004826.4(ECEL1):c.2069G>A (p.Trp690Ter)	ECEL1	Pathogenic	criteria provided, single submitter
210910	NM_004826.4(ECEL1):c.997C>T (p.Arg333Ter)	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
235819	NM_004826.4(ECEL1):c.1184G>A (p.Arg395Gln)	ECEL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
242402	NM_004826.4(ECEL1):c.797_801delinsGCT (p.Asp266fs)	ECEL1	Pathogenic	no assertion criteria provided
242403	NM_004826.4(ECEL1):c.869A>G (p.Tyr290Cys)	ECEL1	Pathogenic	no assertion criteria provided
2444189	NM_004826.4(ECEL1):c.1042del (p.Gln348fs)	ECEL1	Pathogenic	criteria provided, single submitter
2506362	NM_004826.4(ECEL1):c.1059+1G>A	ECEL1	Pathogenic	criteria provided, single submitter
2506368	NM_004826.4(ECEL1):c.1685+1G>A	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
2572395	NM_004826.4(ECEL1):c.1702C>T (p.Gln568Ter)	ECEL1	Pathogenic	criteria provided, single submitter
374305	NM_004826.4(ECEL1):c.1470G>A (p.Trp490Ter)	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
3770938	NM_004826.4(ECEL1):c.966+1G>A	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
39488	NM_004826.4(ECEL1):c.716dup (p.Tyr239Ter)	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
39489	NM_004826.4(ECEL1):c.344_355del (p.Asn115_Ala118del)	ECEL1	Pathogenic	no assertion criteria provided
39490	NM_004826.4(ECEL1):c.1252C>A (p.Arg418Ser)	ECEL1	Pathogenic	no assertion criteria provided
39491	NM_004826.4(ECEL1):c.1184+3A>T	ECEL1	Pathogenic	no assertion criteria provided
435023	NM_004826.4(ECEL1):c.509del (p.Gly170fs)	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
435024	NM_004826.4(ECEL1):c.110_155del (p.Phe37fs)	ECEL1	Pathogenic	criteria provided, multiple submitters, no conflicts
488495	NM_004826.4(ECEL1):c.2151+2T>A	ECEL1	Pathogenic	criteria provided, single submitter
816799	NM_004826.4(ECEL1):c.505_529del (p.Gly169fs)	ECEL1	Pathogenic	no assertion criteria provided
816827	NM_004826.4(ECEL1):c.1147C>T (p.Gln383Ter)	ECEL1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ECEL1	Definitive	Autosomal recessive	distal arthrogryposis type 5D	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ECEL1	Orphanet:329457	Distal arthrogryposis type 5D

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ECEL1	HGNC:3147	ENSG00000171551	O95672	Endothelin-converting enzyme-like 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ECEL1	Endothelin-converting enzyme-like 1	May contribute to the degradation of peptide hormones and be involved in the inactivation of neuronal peptides.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ECEL1	Protease	yes		Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
left ovary	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ECEL1	152	broad	marker	left ovary, right ovary, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ECEL1	1,194

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ECEL1	O95672	88.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
respiratory system process	1	936.2×	0.003	ECEL1
neuropeptide signaling pathway	1	172.0×	0.006	ECEL1
protein processing	1	170.2×	0.006	ECEL1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ECEL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ECEL1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ECEL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.