Nonsyndromic congenital nail disorder 8

Summary

Nonsyndromic congenital nail disorder 8 (MONDO:0011852) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 232

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nonsyndromic congenital nail disorder 8
Mondo ID	MONDO:0011852
MeSH	C564384
OMIM	607523
DOID	DOID:0080086
UMLS	C1843761
MedGen	375277
GARD	0024828
Is cancer (heuristic)	no

Also known as: COL7A1 inherited isolated nail anomaly · inherited isolated nail anomaly caused by mutation in COL7A1 · nail disorder, nonsyndromic congenital, 8 · nail disorder, nonsyndromic congenital, type 8 · NDNC8 · nonsyndromic congenital nail disorder type 8

Data availability: 232 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › nail disorder › inherited isolated nail anomaly › nonsyndromic congenital nail disorder 8

Related subtypes (8): isolated congenital digital clubbing, nonsyndromic congenital nail disorder 2, nonsyndromic congenital nail disorder 3, nonsyndromic congenital nail disorder 1, nonsyndromic congenital nail disorder 5, nonsyndromic congenital nail disorder 7, leukonychia totalis, isolated congenital anonychia

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

232 retrieved; paginated sample, class counts are floors:

57 pathogenic/likely pathogenic, 55 likely pathogenic, 48 conflicting classifications of pathogenicity, 48 pathogenic, 15 uncertain significance, 5 benign/likely benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032188	NM_000094.4(COL7A1):c.8304+1G>A	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047934	NM_000094.4(COL7A1):c.58_70del (p.Arg20fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048003	NM_000094.4(COL7A1):c.3130C>T (p.Gln1044Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048010	NM_000094.4(COL7A1):c.4012G>A (p.Gly1338Arg)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048045	NM_000094.4(COL7A1):c.7270C>T (p.Arg2424Trp)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048050	NM_000094.4(COL7A1):c.7474C>T (p.Arg2492Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048054	NM_000094.4(COL7A1):c.7738C>T (p.Arg2580Cys)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066186	NM_000094.4(COL7A1):c.8020G>C (p.Gly2674Arg)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070885	NM_000094.4(COL7A1):c.565C>T (p.Gln189Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072343	NM_000094.4(COL7A1):c.3830del (p.Pro1277fs)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073113	NM_000094.4(COL7A1):c.4965C>T (p.Gly1655=)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074690	NM_000094.4(COL7A1):c.6501+1G>C	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075255	NM_000094.4(COL7A1):c.1837C>T (p.Arg613Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324153	NM_000094.4(COL7A1):c.6023G>A (p.Arg2008His)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1393079	NM_000094.4(COL7A1):c.8219G>C (p.Gly2740Ala)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1402177	NM_000094.4(COL7A1):c.3636del (p.Phe1213fs)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404275	NM_000094.4(COL7A1):c.6395G>A (p.Gly2132Asp)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404283	NM_000094.4(COL7A1):c.5108G>A (p.Gly1703Glu)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1409788	NM_000094.4(COL7A1):c.3850G>A (p.Gly1284Ser)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1443361	NM_000094.4(COL7A1):c.2785C>T (p.Gln929Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1453658	NM_000094.4(COL7A1):c.3832_3833del	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458606	NM_000094.4(COL7A1):c.5532+5G>A	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1459712	NM_000094.4(COL7A1):c.5107G>T (p.Gly1703Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1492815	NM_000094.4(COL7A1):c.5304_5307+1del	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526043	NM_000094.4(COL7A1):c.5560G>A (p.Gly1854Arg)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
156289	NM_000094.4(COL7A1):c.5443G>A (p.Gly1815Arg)	COL7A1	Pathogenic	no assertion criteria provided
1676611	NM_000094.4(COL7A1):c.7104+3A>T	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1676617	NM_000094.4(COL7A1):c.329_332dup (p.Ser111_Tyr112insTer)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17423	NM_000094.4(COL7A1):c.8393T>A (p.Met2798Lys)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17425	NM_000094.4(COL7A1):c.2471dup (p.Asn825fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL7A1	Orphanet:158673	Localized dystrophic epidermolysis bullosa, acral form
COL7A1	Orphanet:158676	Localized dystrophic epidermolysis bullosa, nails only
COL7A1	Orphanet:231568	Autosomal dominant generalized dystrophic epidermolysis bullosa
COL7A1	Orphanet:79408	Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form
COL7A1	Orphanet:79409	Recessive dystrophic epidermolysis bullosa inversa
COL7A1	Orphanet:79410	Localized dystrophic epidermolysis bullosa, pretibial form
COL7A1	Orphanet:79411	Self-improving dystrophic epidermolysis bullosa
COL7A1	Orphanet:89842	Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form
COL7A1	Orphanet:89843	Dystrophic epidermolysis bullosa pruriginosa

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
COL7A1	HGNC:2214	ENSG00000114270	Q02388	Collagen alpha-1(VII) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL7A1	Collagen alpha-1(VII) chain	Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV c…

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL7A1	Antibody/Immunoglobulin	yes		VWF_A, Kunitz_BPTI, FN3_dom

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
skin of abdomen	1
skin of leg	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL7A1	267	ubiquitous	marker	stromal cell of endometrium, skin of abdomen, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL7A1	1,767

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL7A1	Q02388

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring fibril formation	1	761.3×	0.007	COL7A1
Fibronectin matrix formation	1	571.0×	0.007	COL7A1
Laminin interactions	1	380.7×	0.007	COL7A1
Cargo concentration in the ER	1	335.9×	0.007	COL7A1
Collagen chain trimerization	1	259.6×	0.007	COL7A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL7A1
Collagen degradation	1	175.7×	0.007	COL7A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL7A1
COPII-mediated vesicle transport	1	163.1×	0.007	COL7A1
Integrin cell surface interactions	1	134.3×	0.007	COL7A1

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
endodermal cell differentiation	1	495.6×	0.006	COL7A1
epidermis development	1	210.7×	0.007	COL7A1
cell adhesion	1	37.5×	0.027	COL7A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL7A1	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	COL7A1
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)
COL7A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.