Acanthosis nigricans

Summary

Acanthosis nigricans (MONDO:0007035) is a disease with 2 cohort genes and 14 clinical trials. Top therapeutic interventions include leuprolide, metformin, and spironolactone.

At a glance

• Cohort genes: 2
• ClinVar variants: 4
• Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acanthosis nigricans
Mondo ID	MONDO:0007035
EFO	EFO:1000660
MeSH	D000052
Orphanet	924
DOID	DOID:3138
ICD-10-CM	L83
ICD-11	71488193
NCIT	C26687
SNOMED CT	402599005
UMLS	C0000889
MedGen	54
Is cancer (heuristic)	no

Also known as: acanthosis nigricans · acanthosis nigricans (disease) · an - acanthosis nigricans

Data availability: 4 ClinVar variants · 1 HPO phenotype · 1 cell line.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › acanthosis nigricans

Related subtypes (32): spongiotic dermatitis, atopic eczema, psoriasis, contact dermatitis, urticaria, acneiform dermatitis, acrodermatitis, folliculitis, granuloma annulare, granulomatous dermatitis, lichen planus, neurodermatitis, neurotic excoriation, parapsoriasis, pityriasis rosea, seborrheic dermatitis, dermatosis papulosa nigra, lichen sclerosus et atrophicus, vitiligo, acne, porphyria cutanea tarda, dermatomyositis, acute generalized exanthematous pustulosis, hydroa vacciniforme, autoimmune bullous skin disease, cutaneous vasculitis, skin infection, intertrigo, lipodermatosclerosis, exfoliative dermatitis, radiodermatitis, food dermatitis

Subtypes (2): acanthosis nigricans-insulin resistance-muscle cramps-acral enlargement syndrome, familial acanthosis nigricans

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

4 retrieved; paginated sample, class counts are floors:

1 benign; drug response, 1 uncertain significance, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523434	NM_019023.5(PRMT7):c.1713C>A (p.Cys571Ter)	PRMT7	Pathogenic	criteria provided, multiple submitters, no conflicts
523435	NM_019023.5(PRMT7):c.322G>T (p.Glu108Ter)	PRMT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
130341	NM_018344.6(SLC29A3):c.473C>T (p.Ser158Phe)	SLC29A3	Benign; drug response	criteria provided, multiple submitters, no conflicts
267831	46;Y;inv(X)(q27q28)		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC29A3	Orphanet:168569	H syndrome
SLC29A3	Orphanet:1782	Dysosteosclerosis
PRMT7	Orphanet:464288	Short stature-brachydactyly-obesity-global developmental delay syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC29A3	HGNC:23096	ENSG00000198246	Q9BZD2	Equilibrative nucleoside transporter 3	clinvar
PRMT7	HGNC:25557	ENSG00000132600	Q9NVM4	Protein arginine N-methyltransferase 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC29A3	Equilibrative nucleoside transporter 3	Uniporter that mediates the facilitative transport of nucleoside across lysosomal and mitochondrial membranes.
PRMT7	Protein arginine N-methyltransferase 7	Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC29A3	Other/Unknown	no		Eqnu_transpt
PRMT7	Enzyme (other)	yes	2.1.1.321	MeTrfase_PRMT7, Arg_MeTrfase, SAM-dependent_MTases_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory bulb	1
primordial germ cell in gonad	1
type B pancreatic cell	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC29A3	219	ubiquitous	yes	olfactory bulb, type B pancreatic cell, primordial germ cell in gonad
PRMT7	186	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRMT7	2,036
SLC29A3	864

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRMT7	Q9NVM4	93.19
SLC29A3	Q9BZD2	82.40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC29A3 causes histiocytosis-lymphadenopathy plus syndrome (HLAS)	1	5710.0×	0.002	SLC29A3
Ribavirin ADME	1	519.1×	0.009	SLC29A3
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	475.8×	0.009	SLC29A3
Transport of vitamins, nucleosides, and related molecules	1	135.9×	0.021	SLC29A3
Drug ADME	1	114.2×	0.021	SLC29A3
SLC transporter disorders	1	102.0×	0.021	SLC29A3
RMTs methylate histone arginines	1	73.2×	0.023	PRMT7
Disorders of transmembrane transporters	1	69.6×	0.023	SLC29A3
Chromatin organization	1	40.8×	0.035	PRMT7
Chromatin modifying enzymes	1	36.1×	0.036	PRMT7
SLC-mediated transmembrane transport	1	29.6×	0.040	SLC29A3
Transport of small molecules	1	12.6×	0.084	SLC29A3
Disease	1	6.5×	0.147	SLC29A3

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
pyrimidine nucleobase transmembrane transport	1	4213.0×	0.001	SLC29A3
nucleoside transport	1	2808.7×	0.001	SLC29A3
guanine transmembrane transport	1	2808.7×	0.001	SLC29A3
uracil transmembrane transport	1	2808.7×	0.001	SLC29A3
cytidine transport	1	2106.5×	0.001	SLC29A3
peptidyl-arginine methylation	1	2106.5×	0.001	PRMT7
inosine transport	1	2106.5×	0.001	SLC29A3
obsolete serotonin transport	1	1685.2×	0.001	SLC29A3
nucleobase transport	1	1685.2×	0.001	SLC29A3
adenosine transport	1	1685.2×	0.001	SLC29A3
uridine transmembrane transport	1	1404.3×	0.001	SLC29A3
nucleoside transmembrane transport	1	1404.3×	0.001	SLC29A3
purine nucleobase transmembrane transport	1	1404.3×	0.001	SLC29A3
obsolete norepinephrine transport	1	936.2×	0.002	SLC29A3
obsolete dopamine transport	1	766.0×	0.002	SLC29A3
genomic imprinting	1	495.6×	0.003	PRMT7
spliceosomal snRNP assembly	1	290.6×	0.004	PRMT7
xenobiotic metabolic process	1	74.6×	0.015	SLC29A3
chromatin remodeling	1	36.5×	0.029	PRMT7
regulation of DNA-templated transcription	1	15.8×	0.062	PRMT7

Therapeutics

Drug target analysis

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

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
PRMT7	1	3
SLC29A3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ADEMETIONINE	3	PRMT7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRMT7	100	Binding:98, Functional:2
SLC29A3	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRMT7	2.1.1.321	type III protein arginine methyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PRMT7	100

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
ADEMETIONINE	3	PRMT7

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	1	PRMT7
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SLC29A3

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)
SLC29A3	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE2	2
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02438020	PHASE4	UNKNOWN	Study of Efficacy of Metformin in the Treatment of Acanthosis Nigricans in Children With Obesity
NCT06213987	PHASE3	COMPLETED	The Efficacy Tretinoin Cream in the Treatment of Axillary Hyperpigmentation Associated With Acanthosis Nigricans
NCT00004311	PHASE2	COMPLETED	Phase II Study of the Effect of Leuprolide Acetate and Spironolactone on Insulin Resistance in Hyperandrogenic Women With Polycystic Ovarian Disease or Hyperandrogenism Insulin Resistance Acanthosis Nigricans Syndrome
NCT06940895	PHASE2	COMPLETED	Evaluating the Safety and Efficacy of Topical Sirolimus 0.2% to Treat Acanthosis Nigricans
NCT06331819	Not specified	RECRUITING	Clinical Association Between Obstructive Sleep Apnea, Facial Pigmentation, and Vasovagal Symptoms.
NCT00000112	Not specified	UNKNOWN	Prevalence of Carbohydrate Intolerance in Lean and Obese Children
NCT01125150	Not specified	COMPLETED	Spectroscopic and Colorimetric Analysis of Acanthosis Nigricans in Patients With Hyperinsulinemia
NCT01881373	Not specified	COMPLETED	Children’s Healthy Living Community Randomized Trial
NCT02604095	Not specified	COMPLETED	Effect of Melatonin on Body Composition, Glucose Metabolism and Lipid Metabolism
NCT04893304	Not specified	UNKNOWN	Study of the Effect of Fractional co2 Laser Versus Q Switched:NdYAG Laser in the Treatment of Acanthosis Nigricans
NCT05457439	Not specified	UNKNOWN	Sustainable-psycho-nutritional Intervention Program and Its Effects on Health Outcomes and the Environment
NCT05529563	Not specified	UNKNOWN	The Effect of Laparoscopic Sleeve Gastrectomy on Insulin Secretion Pattern in Morbidly Obese Patients With Acanthosis Nigricans
NCT06008327	Not specified	COMPLETED	Comparison Of Outcome Of Treatment OF Topical 15%TCA VS Topical 0.05% Tretinoin In Treatment Of Acanthosis Nigricans
NCT07371169	Not specified	COMPLETED	Efficacy of Chromium Picolinate in Reducing Acanthosis Nigricans Severity in Adolescents With Insulin Resistance

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LEUPROLIDE	4	3
METFORMIN	4	2
SPIRONOLACTONE	4	1
TRETINOIN	4	1
CHROMIUM PICOLINATE	1	1
CHEMBL1562223	0	1
CHEMBL30458	0	1
2-PICOLINIC ACID	0	1