Pyogenic granuloma

Summary

Pyogenic granuloma (MONDO:0022096) is a disease with 2 cohort genes (6 GWAS associations across 4 studies) and 1 clinical trial.

At a glance

• Cohort genes: 2
• GWAS associations: 6
• ClinVar variants: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pyogenic granuloma
Mondo ID	MONDO:0022096
MeSH	D017789
ICD-10-CM	L98.0
ICD-11	440675859
NCIT	C3480
SNOMED CT	200722003
UMLS	C0085653
MedGen	39085
Is cancer (heuristic)	no

Also known as: angiogranuloma · angiogranulomas · Capillary hemangioma of granulation tissue type · Capillary Hemangioma, Lobular · Granuloma Pyogenicum · Granuloma pyogenicum · Granuloma telangiectaticum · Granuloma Telangiecticum · Granuloma, Pyogenic · hemangioma, Lobular Capillary · Lobular Capillary Hemangioma · Lobular capillary hemangioma · PG - Pyogenic granuloma

Data availability: 2 ClinVar variants · 6 GWAS associations (4 studies).

Disease family

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › benign neoplasm › cardiovascular organ benign neoplasm › benign blood vessel neoplasm › hemangioma › capillary hemangioma › pyogenic granuloma

Related subtypes (5): cherry hemangioma, breast capillary hemangioma, capillary infantile hemangioma, hemangioblastoma, eyelid capillary hemangioma

Genetics & variants

GWAS landscape

6 GWAS associations across 4 studies. Top hits map to 5 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs145080015	9e-15	NTNG1	A	4.04
rs189587536	1e-13	CDH4	T	4.61
rs368835767	2e-13	LINC01698	C	4.13
rs146121743	1e-12	Metazoa_SRP - FAM149B1P1	G	4.17
rs562007239	1e-11	ZNF480	G	4.62
rs145666765	3e-11	LINC02262	C	2.58

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478767	Verma A	2024	790	448,371	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436579	Zhou W	2018	362	397,635	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90480440	Verma A	2024	275	121,138	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482321	Verma A	2024	275	121,138	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

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)	0
low_freq (0.01-0.05)	0
rare (<0.01)	6
unknown	0

Functional consequences

Consequence	Count
intron_variant	6

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs145080015	1	107283476	A>C,G	0.001	intron_variant	NTNG1	9e-15	Tier 4: intronic/intergenic
rs189587536	20	61288987	T>A	0	intron_variant	CDH4	1e-13	Tier 4: intronic/intergenic
rs368835767	1	209370494	C>T	0	intron_variant	LINC01698	2e-13	Tier 4: intronic/intergenic
rs146121743	15	96734051	G>A	0	intron_variant	Metazoa_SRP - FAM149B1P1	1e-12	Tier 4: intronic/intergenic
rs562007239	19	52318913	G>T	0	intron_variant	ZNF480	1e-11	Tier 4: intronic/intergenic
rs145666765	4	117340216	C>T	0.002	intron_variant	LINC02262	3e-11	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
548667	NM_004297.4(GNA14):c.614A>T (p.Gln205Leu)	GNA14	Pathogenic	criteria provided, single submitter
2672090	NM_002524.5(NRAS):c.191_196dup (p.Ser65_Ala66insAspSer)	NRAS	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNA14	Orphanet:1063	Tufted angioma
GNA14	Orphanet:2122	Kaposiform hemangioendothelioma
GNA14	Orphanet:675359	Anastomosing haemangioma
NRAS	Orphanet:146	Differentiated thyroid carcinoma
NRAS	Orphanet:2612	Linear nevus sebaceus syndrome
NRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
NRAS	Orphanet:389	Langerhans cell histiocytosis
NRAS	Orphanet:626	Large/giant congenital melanocytic nevus
NRAS	Orphanet:648	Noonan syndrome
NRAS	Orphanet:86834	Juvenile myelomonocytic leukemia

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
GNA14	HGNC:4382	ENSG00000156049	O95837	Guanine nucleotide-binding protein subunit alpha-14	clinvar
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNA14	Guanine nucleotide-binding protein subunit alpha-14	Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

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)
GNA14	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

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
secondary oocyte	2
bronchial epithelial cell	1
oocyte	1
epithelium of nasopharynx	1
gingival epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNA14	208	broad	marker	secondary oocyte, oocyte, bronchial epithelial cell
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NRAS	7,598
GNA14	1,081

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NRAS	P01111	35

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GNA14	O95837	93.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 77. 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
Signaling by RAS GAP mutants	1	1903.3×	0.007	NRAS
Signaling by RAS GTPase mutants	1	1903.3×	0.007	NRAS
Activation of RAS in B cells	1	1142.0×	0.007	NRAS
RAS signaling downstream of NF1 loss-of-function variants	1	815.7×	0.007	NRAS
Estrogen-stimulated signaling through PRKCZ	1	815.7×	0.007	NRAS
SOS-mediated signalling	1	713.8×	0.007	NRAS
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	713.8×	0.007	GNA14
Activated NTRK3 signals through RAS	1	634.4×	0.007	NRAS
EGFR Transactivation by Gastrin	1	571.0×	0.007	NRAS
SHC-related events triggered by IGF1R	1	571.0×	0.007	NRAS
Acetylcholine regulates insulin secretion	1	571.0×	0.007	GNA14
Activated NTRK2 signals through RAS	1	571.0×	0.007	NRAS
MET activates RAS signaling	1	519.1×	0.007	NRAS
Signaling by FGFR4 in disease	1	475.8×	0.007	NRAS
Activated NTRK2 signals through FRS2 and FRS3	1	475.8×	0.007	NRAS
Constitutive Signaling by Overexpressed ERBB2	1	475.8×	0.007	NRAS
p38MAPK events	1	439.2×	0.007	NRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	439.2×	0.007	NRAS
Signaling by PDGFRA extracellular domain mutants	1	439.2×	0.007	NRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	407.9×	0.007	NRAS
GRB2 events in EGFR signaling	1	380.7×	0.007	NRAS
Erythropoietin activates RAS	1	380.7×	0.007	NRAS
Signaling by FLT3 ITD and TKD mutants	1	380.7×	0.007	NRAS
SHC1 events in ERBB4 signaling	1	356.9×	0.007	NRAS
SHC1 events in EGFR signaling	1	356.9×	0.007	NRAS
Constitutive Signaling by EGFRvIII	1	356.9×	0.007	NRAS
Signalling to RAS	1	335.9×	0.007	NRAS
Insulin receptor signalling cascade	1	335.9×	0.007	NRAS
Signaling by ERBB2 ECD mutants	1	335.9×	0.007	NRAS
GRB2 events in ERBB2 signaling	1	317.2×	0.007	NRAS

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
phospholipase C-activating dopamine receptor signaling pathway	1	1053.2×	0.009	GNA14
action potential	1	179.3×	0.017	GNA14
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	168.5×	0.017	GNA14
positive regulation of endothelial cell proliferation	1	115.4×	0.017	NRAS
Ras protein signal transduction	1	102.8×	0.017	NRAS
cell chemotaxis	1	92.6×	0.017	GNA14
MAPK cascade	1	76.6×	0.017	NRAS
positive regulation of inflammatory response	1	72.6×	0.017	GNA14
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.017	GNA14
signal transduction	1	8.0×	0.121	GNA14

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Hydrocortisone.

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NRAS	1	1
GNA14	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
L-778123 FREE BASE	1	NRAS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NRAS	18	Binding:18

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)
L-778123 FREE BASE	1	NRAS

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	NRAS
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GNA14

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)
GNA14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05692427	Not specified	RECRUITING	Evaluation of Cryotherapy in Granuloma Pyogenicum