Ehlers-Danlos syndrome, classic type, 2

Summary

Ehlers-Danlos syndrome, classic type, 2 (MONDO:0019568) is a disease caused by COL5A2 (GenCC Strong), with 4 cohort genes.

At a glance

• Causal gene: COL5A2 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 255

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, classic type, 2
Mondo ID	MONDO:0019568
MeSH	C536195
OMIM	130010
Orphanet	90318
DOID	DOID:0080726
NCIT	C125697
UMLS	C0268336
MedGen	120628
GARD	0025141
Is cancer (heuristic)	no

Also known as: EDS II · EDSCL2 · Ehlers Danlos syndrome, mild Classic type · Ehlers Danlos syndrome, mitis type · Ehlers-Danlos syndrome, classic type, 2

Data availability: 255 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Ehlers-Danlos syndrome, classic type › Ehlers-Danlos syndrome, classic type, 2

Related subtypes (1): Ehlers-Danlos syndrome, classic type, 1

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

255 retrieved; paginated sample, class counts are floors:

72 benign/likely benign, 66 conflicting classifications of pathogenicity, 56 uncertain significance, 23 benign, 17 likely benign, 13 likely pathogenic, 5 pathogenic, 2 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
930611	NM_000093.5(COL5A1):c.2731C>T (p.Gln911Ter)	COL5A1	Pathogenic	criteria provided, single submitter
1895397	NM_000393.5(COL5A2):c.1105G>A (p.Gly369Ser)	COL5A2	Pathogenic	criteria provided, single submitter
213101	NM_000393.5(COL5A2):c.1977G>A (p.Pro659=)	COL5A2	Pathogenic	criteria provided, multiple submitters, no conflicts
523366	NM_000393.5(COL5A2):c.754G>T (p.Gly252Cys)	COL5A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
529249	NM_000393.5(COL5A2):c.3309+1G>A	COL5A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
976315	NM_000393.5(COL5A2):c.1159-60_2031+62dup	COL5A2	Pathogenic	criteria provided, single submitter
31531	NM_058246.4(DNAJB6):c.265T>A (p.Phe89Ile)	DNAJB6	Pathogenic	criteria provided, multiple submitters, no conflicts
1028727	NM_000393.5(COL5A2):c.2833G>A (p.Gly945Arg)	COL5A2	Likely pathogenic	criteria provided, single submitter
1324127	NM_000393.5(COL5A2):c.98-1G>T	COL5A2	Likely pathogenic	criteria provided, single submitter
1723124	NM_000393.5(COL5A2):c.2553+1G>T	COL5A2	Likely pathogenic	criteria provided, single submitter
1805198	NM_000393.5(COL5A2):c.1907G>C (p.Gly636Ala)	COL5A2	Likely pathogenic	criteria provided, single submitter
2430132	NM_000393.5(COL5A2):c.2285G>A (p.Gly762Asp)	COL5A2	Likely pathogenic	criteria provided, single submitter
2431553	NM_000393.5(COL5A2):c.2031+1G>A	COL5A2	Likely pathogenic	criteria provided, single submitter
2439422	NM_000393.5(COL5A2):c.1159-1G>A	COL5A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627760	NM_000393.5(COL5A2):c.3230del (p.Gly1077fs)	COL5A2	Likely pathogenic	no assertion criteria provided
4755399	NM_000393.5(COL5A2):c.3106_3117del (p.Pro1036_Ser1039del)	COL5A2	Likely pathogenic	criteria provided, single submitter
565322	NM_000393.5(COL5A2):c.369+1G>T	COL5A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
870138	NM_000393.5(COL5A2):c.3490G>C (p.Gly1164Arg)	COL5A2	Likely pathogenic	no assertion criteria provided
977757	NM_000393.5(COL5A2):c.568-316_3525+41del	COL5A2	Likely pathogenic	criteria provided, single submitter
930317	NM_000093.5(COL5A1):c.4804_4805insCGTTCTCTACCAGCTGC (p.Val1602fs)	LOC101448202	Likely pathogenic	criteria provided, single submitter
212943	NM_000093.5(COL5A1):c.1831C>T (p.Arg611Trp)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213017	NM_000093.5(COL5A1):c.754C>T (p.Pro252Ser)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
409120	NM_000093.5(COL5A1):c.3592G>A (p.Gly1198Ser)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
519643	NM_000093.5(COL5A1):c.1304C>T (p.Pro435Leu)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
696848	NM_000093.5(COL5A1):c.57G>A (p.Leu19=)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931041	NM_000093.5(COL5A1):c.1495-7T>A	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136965	NM_000393.5(COL5A2):c.322+8T>C	COL5A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1369746	NM_000393.5(COL5A2):c.1005+3A>G	COL5A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1470109	NM_000393.5(COL5A2):c.1775C>T (p.Ala592Val)	COL5A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
155777	NM_000393.5(COL5A2):c.1976C>T (p.Pro659Leu)	COL5A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 5 · 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
COL5A2	Definitive	Autosomal dominant	Ehlers-Danlos syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL5A2	Orphanet:287	Classical Ehlers-Danlos syndrome
DNAJB6	Orphanet:34516	DNAJB6-related limb-girdle muscular dystrophy D1
DNAJB6	Orphanet:708126	DNAJB6-related distal myopathy
COL5A1	Orphanet:287	Classical Ehlers-Danlos syndrome
AEBP1	Orphanet:536532	Classical-like Ehlers-Danlos syndrome type 2

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	gencc,clinvar
DNAJB6	HGNC:14888	ENSG00000105993	O75190	DnaJ homolog subfamily B member 6	clinvar
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	clinvar
AEBP1	HGNC:303	ENSG00000106624	Q8IUX7	Adipocyte enhancer-binding protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
DNAJB6	DnaJ homolog subfamily B member 6	Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70.
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
AEBP1	Adipocyte enhancer-binding protein 1	As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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	9.2×	0.210
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
DNAJB6	Other/Unknown	no		DnaJ_domain, DnaJ_domain_CS, J_dom_sf
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
AEBP1	Protease	yes		FA58C, Peptidase_M14, CarboxyPept-like_regulatory

Expression context

Cohort genes with no expression data: 0.

4 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tendon of biceps brachii	3
periodontal ligament	2
stromal cell of endometrium	2
cortical plate	1
ganglionic eminence	1
primordial germ cell in gonad	1
ascending aorta	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL5A2	266	ubiquitous	marker	tendon of biceps brachii, periodontal ligament, stromal cell of endometrium
DNAJB6	283	ubiquitous	marker	cortical plate, primordial germ cell in gonad, ganglionic eminence
COL5A1	248	ubiquitous	marker	stromal cell of endometrium, periodontal ligament, tendon of biceps brachii
AEBP1	273	ubiquitous	marker	tendon of biceps brachii, thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNAJB6	3,518
COL5A1	2,600
COL5A2	2,286
AEBP1	1,060

Intra-cohort edges

A	B	Sources
AEBP1	COL5A1	string_interaction
AEBP1	COL5A2	string_interaction
COL5A1	COL5A2	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNAJB6	O75190	4
COL5A1	P20908	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AEBP1	Q8IUX7	67.99
COL5A2	P05997	53.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fibronectin matrix formation	2	380.7×	9e-05	COL5A2, COL5A1
Attachment of bacteria to epithelial cells	2	331.0×	9e-05	COL5A2, COL5A1
Syndecan interactions	2	282.0×	9e-05	COL5A2, COL5A1
MET activates PTK2 signaling	2	253.8×	9e-05	COL5A2, COL5A1
Collagen chain trimerization	2	173.0×	1e-04	COL5A2, COL5A1
Signaling by PDGF	2	169.2×	1e-04	COL5A2, COL5A1
NCAM1 interactions	2	165.5×	1e-04	COL5A2, COL5A1
Developmental Lineage of Pancreatic Ductal Cells	2	152.3×	1e-04	COL5A2, COL5A1
Assembly of collagen fibrils and other multimeric structures	2	133.6×	1e-04	COL5A2, COL5A1
Collagen degradation	2	117.1×	2e-04	COL5A2, COL5A1
Collagen biosynthesis and modifying enzymes	2	113.6×	2e-04	COL5A2, COL5A1
Non-integrin membrane-ECM interactions	2	102.9×	2e-04	COL5A2, COL5A1
ECM proteoglycans	2	100.2×	2e-04	COL5A2, COL5A1
Integrin cell surface interactions	2	89.6×	2e-04	COL5A2, COL5A1
Attenuation phase	1	135.9×	0.009	DNAJB6
HSF1 activation	1	126.9×	0.009	DNAJB6
HSF1-dependent transactivation	1	105.7×	0.010	DNAJB6
Regulation of HSF1-mediated heat shock response	1	46.4×	0.021	DNAJB6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of endodermal cell differentiation	2	4213.0×	1e-06	COL5A2, COL5A1
eye morphogenesis	2	2106.5×	4e-06	COL5A2, COL5A1
skin development	2	221.7×	3e-04	COL5A2, COL5A1
collagen fibril organization	2	112.3×	9e-04	COL5A2, COL5A1
integrin biosynthetic process	1	4213.0×	0.002	COL5A1
syncytiotrophoblast cell differentiation involved in labyrinthine layer development	1	1404.3×	0.003	DNAJB6
chorion development	1	1404.3×	0.003	DNAJB6
regulation of collagen fibril organization	1	1404.3×	0.003	AEBP1
tendon development	1	1053.2×	0.003	COL5A1
chorio-allantoic fusion	1	526.6×	0.006	DNAJB6
negative regulation of inclusion body assembly	1	421.3×	0.007	DNAJB6
nervous system process	1	300.9×	0.008	DNAJB6
collagen biosynthetic process	1	263.3×	0.008	COL5A1
wound healing, spreading of epidermal cells	1	263.3×	0.008	COL5A1
supramolecular fiber organization	1	263.3×	0.008	COL5A1
regulation of cellular response to heat	1	263.3×	0.008	DNAJB6
blood vessel development	1	93.6×	0.019	COL5A1
heart morphogenesis	1	93.6×	0.019	COL5A1
protein localization to nucleus	1	87.8×	0.019	DNAJB6
cellular response to amino acid stimulus	1	76.6×	0.021	COL5A2
intermediate filament organization	1	60.2×	0.025	DNAJB6
regulation of protein localization	1	51.4×	0.028	DNAJB6
skeletal system development	1	31.4×	0.043	COL5A2
extracellular matrix organization	1	30.5×	0.043	DNAJB6
protein folding	1	25.9×	0.049	DNAJB6
actin cytoskeleton organization	1	19.8×	0.061	DNAJB6
cell migration	1	15.4×	0.075	COL5A1
cell adhesion	1	9.4×	0.117	COL5A1
proteolysis	1	8.6×	0.123	AEBP1
regulation of DNA-templated transcription	1	7.9×	0.125	AEBP1

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL5A2	0	0
DNAJB6	0	0
COL5A1	0	0
AEBP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
DNAJB6	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	AEBP1
E	Difficult family or no structure, no drug	3	COL5A2, DNAJB6, COL5A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL5A2	0	—
DNAJB6	2	—
COL5A1	0	—
AEBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.