Nail disorder

Summary

Nail disorder (MONDO:0002884) is a disease (an umbrella term covering 7 Mondo subtypes) with 1 cohort gene (7 GWAS associations across 10 studies) and 9 clinical trials. Top therapeutic interventions include amorolfine, polihexanide, and terbinafine.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 7
• ClinVar variants: 2
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nail disorder
Mondo ID	MONDO:0002884
MeSH	D009260
DOID	DOID:4123
SNOMED CT	17790008
UMLS	C0027339
MedGen	10171
Anatomy (UBERON)	UBERON:0001705
Is cancer (heuristic)	no

Also known as: disease of nail · disease or disorder of nail · disorder of nail · nail disease · nail disease or disorder

Data availability: 2 ClinVar variants · 7 GWAS associations (10 studies).

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › nail disorder

Related subtypes (35): Neu-Laxova syndrome, cutaneous mycosis, integumentary system benign neoplasm, integumentary system cancer, nipple neoplasm, disorder of pilosebaceous unit, Bartholin duct cyst, benign mammary dysplasia, skin disorder, breast fibrosis, breast mucosa-associated lymphoid tissue lymphoma, panniculitis, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, autosomal dominant deafness - onychodystrophy syndrome, keratoderma hereditarium mutilans, Rombo syndrome, Sjogren-Larsson syndrome, mucosulfatidosis, ichthyosis prematurity syndrome, ANE syndrome, frontonasal dysplasia with alopecia and genital anomaly, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, cutis laxa, X-linked ichthyosis syndrome, demodicidosis, Proteus-like syndrome, familial atypical multiple mole melanoma syndrome, familial tumoral calcinosis, subcutaneous tissue disorder, Bartholin gland neoplasm, pseudoxanthoma elasticum (inherited or acquired), skin appendage disorder, keratinization disease, paraneoplastic cutaneous syndrome

Subtypes (7): paronychia, nail tumor, nail anomaly, inherited isolated nail anomaly, Basaran Yilmaz syndrome, Judge Misch wright syndrome, nail infection

Genetics & variants

GWAS landscape

7 GWAS associations across 10 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1421085	1e-29	FTO	T	0.08
rs7903146	2e-14	TCF7L2	C	0.06
rs35225200	1e-11	BANK1 - SLC39A8	A	0.09
rs2771885	2e-08	SRIP2 - TGIF2LX	?
chrX:155880980	3e-08		C	1.61
chr1:148533707	4e-08		A	2.73

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476207	Verma A	2024	41,535	382,219	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478815	Verma A	2024	12,925	99,922	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480472	Verma A	2024	12,925	99,922	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473955	UK Biobank Whole-Genome Sequencing Consortium	2025	10,709	447,731	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667799	UK Biobank Whole-Genome Sequencing Consortium	2025	10,709	447,731	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90478814	Verma A	2024	4,055	52,334	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436623	Zhou W	2018	1,287	402,357	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90482357	Verma A	2024	263	6,372	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473956	UK Biobank Whole-Genome Sequencing Consortium	2025	211	9,402	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90651533	Liu TY	2025	169	231,046	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	6

MAF distribution

Bucket	Variants
common (>=0.05)	4
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	3
unknown	2
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1421085	16	53767042	T>C	0.407	intron_variant	FTO	1e-29	Tier 4: intronic/intergenic
rs7903146	10	112998590	C>G,T	0.289	intron_variant	TCF7L2	2e-14	Tier 4: intronic/intergenic
rs35225200	4	102225731	A>C	0.086	intron_variant	BANK1 - SLC39A8	1e-11	Tier 4: intronic/intergenic
rs2771885	X	89814155	C>G,T	0.05	intergenic_variant	SRIP2 - TGIF2LX	2e-08	Tier 4: intronic/intergenic
chrX:155880980							3e-08	Tier 4: intronic/intergenic
chr1:148533707							4e-08	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30355	NM_003506.4(FZD6):c.1750G>T (p.Glu584Ter)	FZD6	Pathogenic	no assertion criteria provided
30356	NM_003506.4(FZD6):c.1531C>T (p.Arg511Cys)	FZD6	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FZD6	Orphanet:280654	Autosomal recessive nail dysplasia

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
FZD6	HGNC:4044	ENSG00000164930	O60353	Frizzled-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FZD6	Frizzled-6	Receptor for Wnt proteins.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FZD6	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM

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
bronchial epithelial cell	1
caput epididymis	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FZD6	260	ubiquitous	marker	bronchial epithelial cell, caput epididymis, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FZD6	1,337

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FZD6	O60353	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Signaling by RNF43 mutants	1	1268.9×	0.004	FZD6
Regulation of FZD by ubiquitination	1	519.1×	0.005	FZD6
PCP/CE pathway	1	300.5×	0.006	FZD6
Class B/2 (Secretin family receptors)	1	190.3×	0.006	FZD6
Ca2+ pathway	1	178.4×	0.006	FZD6

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
midbrain morphogenesis	1	4213.0×	1e-03	FZD6
cell proliferation in midbrain	1	3370.4×	1e-03	FZD6
embryonic nail plate morphogenesis	1	3370.4×	1e-03	FZD6
establishment of body hair planar orientation	1	3370.4×	1e-03	FZD6
non-canonical Wnt signaling pathway	1	581.1×	0.004	FZD6
Wnt signaling pathway, planar cell polarity pathway	1	455.5×	0.005	FZD6
hair follicle development	1	383.0×	0.005	FZD6
inner ear morphogenesis	1	300.9×	0.005	FZD6
platelet activation	1	267.5×	0.005	FZD6
neural tube closure	1	187.2×	0.007	FZD6
canonical Wnt signaling pathway	1	153.2×	0.008	FZD6
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.009	FZD6
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	FZD6

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
FZD6	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	1	FZD6
D	Druggable family + AlphaFold only, no drug	0
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)
FZD6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	6
Not specified	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01330706	PHASE4	COMPLETED	Efficacy of Intraoperative Surgical Scrubbing in Reducing Bacterial Load After Nail Removal Surgery
NCT03991936	PHASE4	COMPLETED	Benefit of Placebo and Different Concentrations of Triamcinolone Acetonide in Nail Psoriasis
NCT04384679	PHASE4	WITHDRAWN	Benefit of Topical Hemostatic Powder Containing Hydrophilic Polymer With Potassium Ferrate for Hemostasis Following Nail Surgery
NCT04422795	PHASE4	WITHDRAWN	The Evaluation of External Thermomechanical Stimulation for Pain Reduction in Patients Undergoing Nail Injection
NCT04941807	PHASE4	COMPLETED	Use of Platelet-rich Plasma (PRP) Therapy in Patients With Brittle Nail Syndrome
NCT05544734	PHASE4	COMPLETED	Hydrocodone Compared to Acetaminophen and Ibuprofen for Post-nail Procedure Analgesia
NCT00925418	PHASE3	COMPLETED	Evaluation of the Cryotherapy in the Prevention of Nails Toxicity Induced by Taxotere® in Breast or Prostate Cancer
NCT05482763	Not specified	ACTIVE_NOT_RECRUITING	Mycosis Culture Collection From Dermatological Isolated
NCT04092413	Not specified	UNKNOWN	Subclinical Nail Involvement in Relevant Skin Diseases

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AMOROLFINE	4	1
POLIHEXANIDE	4	1
TERBINAFINE	4	1
TRIAMCINOLONE ACETONIDE	4	1