Contact dermatitis due to nickel

Summary

Contact dermatitis due to nickel (MONDO:0005481) is a disease with 2 cohort genes (2 GWAS associations across 1 studies).

At a glance

• Cohort genes: 2
• GWAS associations: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	contact dermatitis due to nickel
Mondo ID	MONDO:0005481
SNOMED CT	93419003
UMLS	C0684345
MedGen	671387
Is cancer (heuristic)	no

Data availability: 2 GWAS associations (1 study).

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › contact dermatitis › contact dermatitis due to nickel

Related subtypes (3): allergic contact dermatitis, irritant dermatitis, occupational dermatitis

Genetics & variants

GWAS landscape

2 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2367563	4e-06	NTN4, PGAM1P5	A	5.92
rs6733160	7e-06	PELI1	C	9.28

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002108	Kim DS	2013	24	0	A genome-wide association study in Koreans identifies susceptibility loci for allergic nickel dermatitis.

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	2

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2367563	12	95663408	A>C,G,T	0.05	intron_variant	NTN4, PGAM1P5	4e-06	Tier 4: intronic/intergenic
rs6733160	2	64137498	T>C,G	0.05	intron_variant	PELI1	7e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MLF2	HGNC:7126	ENSG00000089693	Q15773	Myeloid leukemia factor 2	gwas
PELI1	HGNC:8827	ENSG00000197329	Q96FA3	E3 ubiquitin-protein ligase pellino homolog 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PELI1	E3 ubiquitin-protein ligase pellino homolog 1	E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MLF2	Other/Unknown	no		Myeloid_leukemia_factor
PELI1	Other/Unknown	no		Pellino_fam, Pellino_FHA, Pellino_RING

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	1
right frontal lobe	1
right hemisphere of cerebellum	1
cartilage tissue	1
mucosa of paranasal sinus	1
pharyngeal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MLF2	292	ubiquitous	marker	right frontal lobe, right hemisphere of cerebellum, cerebellar hemisphere
PELI1	286	ubiquitous	marker	cartilage tissue, mucosa of paranasal sinus, pharyngeal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MLF2	1,447
PELI1	1,189

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PELI1	Q96FA3	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MLF2	Q15773	65.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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
IRAK1 recruits IKK complex	1	815.7×	0.002	PELI1
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation	1	815.7×	0.002	PELI1
Regulation of necroptotic cell death	1	439.2×	0.003	PELI1
Interleukin-1 signaling	1	124.1×	0.008	PELI1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of Toll signaling pathway	1	2808.7×	0.004	PELI1
response to dsRNA	1	2808.7×	0.004	PELI1
positive regulation of toll-like receptor 3 signaling pathway	1	1203.7×	0.006	PELI1
regulation of necroptotic process	1	936.2×	0.006	PELI1
positive regulation of toll-like receptor 4 signaling pathway	1	495.6×	0.007	PELI1
negative regulation of necroptotic process	1	495.6×	0.007	PELI1
T cell proliferation	1	191.5×	0.012	PELI1
positive regulation of double-strand break repair via homologous recombination	1	191.5×	0.012	PELI1
positive regulation of B cell proliferation	1	172.0×	0.012	PELI1
negative regulation of T cell proliferation	1	165.2×	0.012	PELI1
negative regulation of TORC1 signaling	1	162.0×	0.012	PELI1
positive regulation of cytokine production	1	135.9×	0.012	PELI1
protein K63-linked ubiquitination	1	133.8×	0.012	PELI1
positive regulation of protein ubiquitination	1	106.7×	0.014	PELI1
protein K48-linked ubiquitination	1	84.3×	0.017	PELI1
response to lipopolysaccharide	1	62.4×	0.021	PELI1
protein polyubiquitination	1	57.7×	0.021	PELI1
positive regulation of canonical NF-kappaB signal transduction	1	36.3×	0.032	PELI1
DNA repair	1	31.9×	0.034	PELI1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	26.1×	0.040	PELI1
regulation of DNA-templated transcription	1	15.8×	0.062	MLF2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
MLF2	0	0
PELI1	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
PELI1	2	Binding:2
MLF2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
E	Difficult family or no structure, no drug	2	MLF2, PELI1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MLF2	1	—
PELI1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.