Hemangioma

Summary

Hemangioma (MONDO:0006500) is a disease (an umbrella term covering 28 Mondo subtypes) with 8 cohort genes (7 GWAS associations across 12 studies) and 36 clinical trials. Top therapeutic interventions include timolol, propranolol, and prednisolone.

At a glance

• Umbrella term: 28 Mondo subtypes
• Cohort genes: 8
• GWAS associations: 7
• ClinVar variants: 11
• Clinical trials: 36

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemangioma
Mondo ID	MONDO:0006500
EFO	EFO:1000635
MeSH	D006391
DOID	DOID:255
ICD-10-CM	D18.0
NCIT	C3085
SNOMED CT	400210000
UMLS	C0018916
MedGen	5477
Is cancer (heuristic)	no

Also known as: benign hemangioma · hemangioma · hemangioma, benign

Data availability: 11 ClinVar variants · 7 GWAS associations (12 studies) · 1 HPO phenotype · 1 cell line.

Disease family

An umbrella term covering 28 Mondo subtypes.

Classification path: disease › 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

Related subtypes (2): capillary lymphangioma, angiomatosis

Subtypes (28): malignant hemangioma, arteriovenous hemangioma/malformation, hemangioma of orbit, intra-abdominal hemangioma, capillary hemangioma, venous hemangioma, deep hemangioma, skin hemangioma, subglottic hemangioma, breast hemangioma, cavernous hemangioma, glomeruloid hemangioma, hemangioma of lung, acquired hemangioma, central nervous system hemangioma, hobnail hemangioma, synovial angioma, placental hemangioma, hemangioma of subcutaneous tissue, hemangiomas of small intestine, spindle cell hemangioma, infantile hemangioma of rare localization, congenital hemangioma, epithelioid hemangioma, hemangioma of retina, hemangioma of choroid, hemangioma of gingiva, diffuse cavernous hemangioma of the rectum

Genetics & variants

GWAS landscape

7 GWAS associations across 12 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1027038	1e-18	PCAT1	G	0.13
rs12678465	1e-17	PCAT1	G	0.13
rs13030042	6e-14	CASP8	T	0.11
rs536787956	2e-12	KLHL1	G	4.16
rs528945713	4e-11	MTERF1 - AKAP9	G	1.98
rs74631498	1e-07	TULP4	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475632	Verma A	2024	10,016	420,568	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079671	Backman JD	2021	2,097	384,010	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083657	Backman JD	2021	2,097	384,010	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90079670	Backman JD	2021	1,813	386,087	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083656	Backman JD	2021	1,813	386,087	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90435682	Zhou W	2018	1,603	407,358	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90043612	Jiang L	2021	1,266	455,082	A generalized linear mixed model association tool for biobank-scale data.
GCST90651890	Liu TY	2025	891	235,668	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90477294	Verma A	2024	676	119,980	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479858	Verma A	2024	676	119,980	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)	3
low_freq (0.01-0.05)	0
rare (<0.01)	2
unknown	1

Functional consequences

Consequence	Count
intron_variant	5
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1027038	8	126990244	G>A,T	0.361	intron_variant	PCAT1	1e-18	Tier 4: intronic/intergenic
rs12678465	8	126990627	G>A,T	0.394	intron_variant	PCAT1	1e-17	Tier 4: intronic/intergenic
rs13030042	2	201273662	T>C,G	0.368	intron_variant	CASP8	6e-14	Tier 4: intronic/intergenic
rs536787956	13	69751343	G>A	0	intron_variant	KLHL1	2e-12	Tier 4: intronic/intergenic
rs528945713	7	91931760	G>A	0	intergenic_variant	MTERF1 - AKAP9	4e-11	Tier 4: intronic/intergenic
rs74631498	6	158367018	C>T		intron_variant	TULP4	1e-07	Tier 4: intronic/intergenic

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 3 pathogenic, 3 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
267837	46;XY;t(7;13)(p15.3;q14.1)dn		Pathogenic	criteria provided, single submitter
523383	NM_000969.5(RPL5):c.74-1G>C	DIPK1A	Pathogenic	criteria provided, single submitter
404162	NM_000314.8(PTEN):c.675T>G (p.Tyr225Ter)	PTEN	Pathogenic	criteria provided, multiple submitters, no conflicts
267804	46;XX;ins(3;1)(q23;p22p32)dn		Likely pathogenic	criteria provided, single submitter
267892	46;XX;t(4;14)(p15.2;q13)dn		Likely pathogenic	criteria provided, single submitter
1804036	NM_001256071.3(RNF213):c.114C>G (p.Asn38Lys)	RNF213	Likely pathogenic	criteria provided, single submitter
523386	NM_001009944.3(PKD1):c.359T>C (p.Ile120Thr)	PKD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
268019	46;XY;t(1;4)(q32;q11)		Uncertain significance	criteria provided, single submitter
635772	GRCh37/hg19 14q24.1(chr14:68126321-68269053)x3	ARG2	Uncertain significance	no assertion criteria provided
632442	NM_024592.5(SRD5A3):c.951_955del (p.Phe318fs)	SRD5A3-AS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
523292	GRCh37/hg19 8q23.3(chr8:114378494-114450308)	CSMD3	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 19 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF213	Orphanet:2573	Moyamoya disease
PKD1	Orphanet:730	Autosomal dominant polycystic kidney disease
PKD1	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
PRKD1	Orphanet:276145	Malignant epithelial tumor of salivary glands
PRKD1	Orphanet:708019	Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy

Cohort genes → proteins

8 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF213	HGNC:14539	ENSG00000173821	Q63HN8	E3 ubiquitin-protein ligase RNF213	clinvar
CSMD3	HGNC:19291	ENSG00000164796	Q7Z407	CUB and sushi domain-containing protein 3	clinvar
DIPK1A	HGNC:32213	ENSG00000154511	Q5T7M9	Divergent protein kinase domain 1A	clinvar
SRD5A3-AS1	HGNC:44138	ENSG00000249700		SRD5A3 antisense RNA 1	clinvar
ARG2	HGNC:664	ENSG00000081181	P78540	Arginase-2, mitochondrial	clinvar
PKD1	HGNC:9008	ENSG00000008710	P98161	Polycystin-1	clinvar
PRKD1	HGNC:9407	ENSG00000184304	Q15139	Serine/threonine-protein kinase D1	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF213	E3 ubiquitin-protein ligase RNF213	Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.
CSMD3	CUB and sushi domain-containing protein 3	Involved in dendrite development.
ARG2	Arginase-2, mitochondrial	May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis.
PKD1	Polycystin-1	Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B.
PRKD1	Serine/threonine-protein kinase D1	Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and tr…
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 6 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.75

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
Complement	1	33.5×	0.110
Kinase	2	6.9×	0.110
Phosphatase	1	10.5×	0.213
Antibody/Immunoglobulin	1	3.6×	0.426
Enzyme (other)	1	1.5×	0.702
Transcription factor	1	1.0×	0.751
Other/Unknown	1	0.2×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF213	Transcription factor	no		Znf_RING, AAA+_ATPase, Znf_RING/FYVE/PHD
CSMD3	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
DIPK1A	Kinase	yes		FAM69_kinase_dom, FAM69_N
SRD5A3-AS1	Other/Unknown	no
ARG2	Enzyme (other)	yes	3.5.3.1	Ureohydrolase, Arginase, Ureohydrolase_Mn_BS
PKD1	Antibody/Immunoglobulin	yes		GPS, LRRNT, PC1
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	2
middle temporal gyrus	2
endothelial cell	2
sperm	2
granulocyte	1
metanephros cortex	1
pancreatic ductal cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
left testis	1
right testis	1
cortical plate	1
oocyte	1
tendon of biceps brachii	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
seminal vesicle	1
thoracic aorta	1
ventricular zone	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF213	252	ubiquitous	marker	granulocyte, metanephros cortex, pancreatic ductal cell
CSMD3	129	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, male germ line stem cell (sensu Vertebrata) in testis
DIPK1A	275	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus
SRD5A3-AS1	162	tissue_specific	marker	sperm, left testis, right testis
ARG2	269	ubiquitous	marker	tendon of biceps brachii, oocyte, cortical plate
PKD1	290		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTEN	11,626
ARG2	3,757
RNF213	2,368
PRKD1	2,131
PKD1	1,370
CSMD3	1,264
DIPK1A	575
SRD5A3-AS1	0

Intra-cohort edges

A	B	Sources
PKD1	PRKD1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARG2	P78540	18
PKD1	P98161	13
PTEN	P60484	12
RNF213	Q63HN8	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DIPK1A	Q5T7M9	83.20
PRKD1	Q15139	68.99
CSMD3	Q7Z407

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PTEN Loss of Function in Cancer	1	1142.0×	0.028	PTEN
Suppression of apoptosis	1	326.3×	0.028	RNF213
Response of Mtb to phagocytosis	1	285.5×	0.028	RNF213
Regulation of PTEN mRNA translation	1	228.4×	0.028	PTEN
Infection with Mycobacterium tuberculosis	1	228.4×	0.028	RNF213
Regulation of PTEN localization	1	207.6×	0.028	PTEN
Urea cycle	1	175.7×	0.028	ARG2
VxPx cargo-targeting to cilium	1	103.8×	0.042	PKD1
Synthesis of IP3 and IP4 in the cytosol	1	84.6×	0.043	PTEN
Bacterial Infection Pathways	1	67.2×	0.043	RNF213
Transcriptional Regulation by MECP2	1	63.4×	0.043	PTEN
Sphingolipid de novo biosynthesis	1	57.1×	0.043	PRKD1
Negative regulation of the PI3K/AKT network	1	55.7×	0.043	PTEN
Ovarian tumor domain proteases	1	55.7×	0.043	PTEN
Signaling by ALK in cancer	1	54.4×	0.043	RNF213
Synthesis of PIPs at the plasma membrane	1	42.3×	0.051	PTEN
Regulation of PTEN stability and activity	1	36.8×	0.054	PTEN
Regulation of PTEN gene transcription	1	35.7×	0.054	PTEN
Sphingolipid metabolism	1	33.6×	0.054	PRKD1
Signaling by ALK fusions and activated point mutants	1	30.1×	0.057	RNF213
TP53 Regulates Metabolic Genes	1	25.9×	0.061	PTEN
Downstream TCR signaling	1	25.7×	0.061	PTEN
Mitochondrial protein degradation	1	22.8×	0.065	ARG2
Metabolism	2	4.7×	0.091	ARG2, PRKD1
Class I MHC mediated antigen processing & presentation	1	14.0×	0.097	RNF213
Metabolism of amino acids and derivatives	1	13.5×	0.097	ARG2
Diseases of signal transduction by growth factor receptors and second messengers	1	11.4×	0.110	RNF213
Ub-specific processing proteases	1	10.6×	0.113	PTEN
Antigen processing: Ubiquitination & Proteasome degradation	1	7.4×	0.154	RNF213
Metabolism of lipids	1	6.3×	0.174	PRKD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of chemokine (C-C motif) ligand 4 production	1	2808.7×	0.013	ARG2
metanephric distal tubule morphogenesis	1	2808.7×	0.013	PKD1
lipid ubiquitination	1	2808.7×	0.013	RNF213
regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril	1	1404.3×	0.013	PRKD1
nitrogen cycle metabolic process	1	1404.3×	0.013	PKD1
mesonephric tubule development	1	1404.3×	0.013	PKD1
negative regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1	1404.3×	0.013	ARG2
negative regulation of synaptic vesicle clustering	1	1404.3×	0.013	PTEN
lymph vessel morphogenesis	1	936.2×	0.013	PKD1
negative regulation of keratinocyte migration	1	936.2×	0.013	PTEN
negative regulation of macrophage inflammatory protein 1 alpha production	1	936.2×	0.013	ARG2
metanephric proximal tubule development	1	936.2×	0.013	PKD1
negative regulation of defense response to bacterium	1	936.2×	0.013	ARG2
calcium-independent cell-matrix adhesion	1	702.2×	0.013	PKD1
rhythmic synaptic transmission	1	702.2×	0.013	PTEN
cellular response to norepinephrine stimulus	1	702.2×	0.013	PRKD1
metanephric ascending thin limb development	1	702.2×	0.013	PKD1
mesonephric duct development	1	561.7×	0.013	PKD1
negative regulation of non-canonical Wnt signaling pathway	1	561.7×	0.013	RNF213
negative regulation of type 2 immune response	1	468.1×	0.013	ARG2
central nervous system myelin maintenance	1	468.1×	0.013	PTEN
positive regulation of sarcomere organization	1	468.1×	0.013	PRKD1
negative regulation of chemokine (C-C motif) ligand 5 production	1	468.1×	0.013	ARG2
mitocytosis	1	468.1×	0.013	PKD1
arginine metabolic process	1	401.2×	0.013	ARG2
negative regulation of interleukin-13 production	1	401.2×	0.013	ARG2
xenophagy	1	401.2×	0.013	RNF213
negative regulation of cell cycle G1/S phase transition	1	401.2×	0.013	PTEN
negative regulation of wound healing, spreading of epidermal cells	1	401.2×	0.013	PTEN
regulation of interleukin-1 beta production	1	351.1×	0.013	ARG2

Therapeutics

Drugs indicated for this disease

0 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acebutolol	Phase 3 (in late-stage trials)
Atenolol	Phase 3 (in late-stage trials)
Nadolol	Phase 3 (in late-stage trials)
Propranolol	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Imiquimod, Mupirocin, Prednisolone, Prednisone, Timolol, Vincristine.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 6

Druggability breadth: 5 of 8 evidence-associated genes (62%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PRKD1	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKD1	26	4
ARG2	2	2
RNF213	0	0
CSMD3	0	0
DIPK1A	0	0
SRD5A3-AS1	0	0
PKD1	0	0
PTEN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
NUMIDARGISTAT	2	ARG2
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
NOR-NOHA	1	ARG2
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PRKD1	660	Binding:650, Functional:10
ARG2	37	Binding:34, Functional:3
PKD1	27	Binding:27
PTEN	8	Binding:8
RNF213	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ARG2	3.5.3.1	arginase
PRKD1	2.7.11.13	protein kinase C
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRKD1	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

28 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)
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
NUMIDARGISTAT	2	ARG2
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
NOR-NOHA	1	ARG2
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKD1
B	Phased (≥1) drug, not yet approved	1	ARG2
C	Druggable family + PDB, no drug	2	PKD1, PTEN
D	Druggable family + AlphaFold only, no drug	2	CSMD3, DIPK1A
E	Difficult family or no structure, no drug	2	RNF213, SRD5A3-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1
RNF213	1	—
CSMD3	0	—
DIPK1A	0	—
SRD5A3-AS1	0	—
PTEN	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 36.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	21
PHASE2	6
PHASE3	4
PHASE4	2
EARLY_PHASE1	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01908972	PHASE4	COMPLETED	The Safety and Efficiency of Propranolol as an Initial Treatment for Pediatric Hemangioma
NCT04077515	PHASE4	COMPLETED	Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma
NCT00312520	PHASE3	COMPLETED	Pulse Steroids Versus Oral Steroids in Problematic Hemangiomas of Infancy
NCT01685398	PHASE3	COMPLETED	Topical Timolol for Superficial Infantile Hemangioma
NCT01743885	PHASE3	TERMINATED	Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma
NCT02342275	PHASE3	COMPLETED	Efficacy and Safety of Propranolol Versus Atenolol on the Proliferative Phase of Infantile Hemangioma
NCT07477548	PHASE2	NOT_YET_RECRUITING	A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies
NCT00555464	PHASE2	TERMINATED	Clinical Trial of Vincristine vs. Prednisolone for Treatment of Complicated Hemangiomas
NCT01072045	PHASE2	COMPLETED	Comparative Study of the Use of Beta Blocker and Oral Corticosteroid in the Treatment of Infantile Hemangioma
NCT01074437	PHASE2	TERMINATED	Corticosteroids With Placebo Versus Corticosteroids With Propranolol Treatment of Infantile Hemangiomas (IH)
NCT02145884	PHASE2	COMPLETED	Topical Timolol Gel for the Treatment of Infantile Hemangiomas
NCT02731287	PHASE2	COMPLETED	Topical Timolol for Infantile Hemangioma in Early Proliferative Phase
NCT02496013	PHASE1	UNKNOWN	Clinical Translation of a Novel Albumin-Binding PET Radiotracer 68Ga-NEB
NCT01147601	EARLY_PHASE1	TERMINATED	Topical Timolol 0.5% Solution for Proliferating Infantile Hemangiomas
NCT04020419	EARLY_PHASE1	TERMINATED	Natural Berry Extract Treatment of Hemangiomas
NCT01873131	Not specified	RECRUITING	A Clinical Trial of Pulsed-dye Laser Versus Timolol Topical Solution Versus Observation on the Growth of Hemangioma in Newborn
NCT07418294	Not specified	RECRUITING	Fluctuational Imaging for the Diagnosis of Hepatic Hemangioma: A Multicenter, Prospective Study
NCT00001417	Not specified	COMPLETED	Direct Injection of Alcohol for the Treatment of Spinal Tumors
NCT00004436	Not specified	COMPLETED	Randomized Study of Hormonal Regulation of Infantile Hemangioma
NCT00374335	Not specified	COMPLETED	Incidence of Hepatic Hemangiomatosis in Patients With Cutaneous Hemangiomas
NCT00394888	Not specified	COMPLETED	Hemangioma Associated With High Rates of Morbidity
NCT00433940	Not specified	COMPLETED	Immune Suppression Of Infants Treated With Steroids
NCT00490607	Not specified	UNKNOWN	A Prospective Study Comparing the Incidence of Infantile Hemangiomas Following Normal Pregnancies Versus Pregnancies Complicated by Placental Abnormalities
NCT00540566	Not specified	COMPLETED	Optical Biopsy of Human Skin in Conjunction With Laser Treatment
NCT00576888	Not specified	COMPLETED	Registry for Vascular Anomalies Associated With Coagulopathy
NCT00577213	Not specified	COMPLETED	Diagnosis of Hemangiomas and Vascular Malformations
NCT00866827	Not specified	COMPLETED	Airway Vascular Lesions
NCT00974129	Not specified	WITHDRAWN	A Study of CCCTC-binding Factor (CTCF) in Infantile Hemangiomas
NCT01211080	Not specified	COMPLETED	Off Label Use of Propranolol for Infancy Hemangiomas
NCT01598116	Not specified	COMPLETED	A Prospective Longitudinal Study to Identify Biomarkers in Children With Hemangiomas
NCT02334930	Not specified	COMPLETED	Evaluation of New Biomarkers Predictive of Efficacy Betablockers in PEComa and Vascular Pediatric Tumors
NCT02351245	Not specified	UNKNOWN	Clinical Characteristics of Lip Hemangiomas
NCT03331744	Not specified	UNKNOWN	Clinical Characteristics of Infantile Hemangioma
NCT04065217	Not specified	COMPLETED	The Effectiveness of Diode Laser 980-nm in Iraqi Face Hemangioma: a Randomized Within Patients Trial
NCT04836884	Not specified	COMPLETED	Vascular Anomaly Pathology and Genomics Biopsy Study
NCT05327309	Not specified	COMPLETED	Role of Propranolol as Compared to Bleomycin in Management of Hemangioma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TIMOLOL	4	9
PROPRANOLOL	4	8
PREDNISOLONE	4	4
ACEBUTOLOL	4	1
ATENOLOL	4	1
BLEOMYCIN	4	1
DEXPROPRANOLOL	2	2
ESATENOLOL	2	1
LEVOPROPRANOLOL	2	1
CHEMBL1744069	0	2
CHEMBL1230004	0	1
CHEMBL4073387	0	1