Lymphatic malformation 10

Summary

Lymphatic malformation 10 (MONDO:0023662) is a disease caused by ANGPT2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ANGPT2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphatic malformation 10
Mondo ID	MONDO:0023662
OMIM	619369
UMLS	C5543531
MedGen	1780452
GARD	0025374
Is cancer (heuristic)	no

Also known as: LMPHM10

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › lymphatic malformation › lymphatic malformation 10

Related subtypes (27): microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, lymphatic malformation 1, lymphatic malformation 5, yellow nail syndrome, lymphedema-distichiasis syndrome, campomelia, Cumming type, Dahlberg-Borer-Newcomer syndrome, Norman-Roberts syndrome, anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome, MPI-congenital disorder of glycosylation, hypotrichosis-lymphedema-telangiectasia syndrome, lymphatic malformation 2, lymphatic malformation 3, deafness-lymphedema-leukemia syndrome, lymphatic malformation 4, lymphatic malformation 6, lymphatic malformation 7, Hennekam syndrome, Noonan syndrome, hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, lymphatic malformation 9, lymphatic malformation 11, lymphatic malformation 12, lymphatic malformation 8, congenital primary lymphedema of Gordon, lymphatic malformation 13, lymphatic malformation 14

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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1141561	NM_001118887.2(ANGPT2):c.893C>T (p.Thr298Met)	ANGPT2	Pathogenic	no assertion criteria provided
1141562	NM_001118887.2(ANGPT2):c.1301G>C (p.Cys434Ser)	ANGPT2	Pathogenic	no assertion criteria provided
1141560	NC_000008.11:g.(?6499632)(6563245_?)del	LOC126860291	Pathogenic	no assertion criteria provided
3362424	NM_001118887.2(ANGPT2):c.958G>C (p.Gly320Arg)	ANGPT2	Uncertain significance	criteria provided, single submitter
4292058	NM_001118887.2(ANGPT2):c.160C>T (p.Arg54Cys)	ANGPT2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ANGPT2	Strong	Semidominant	lymphatic malformation 10	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANGPT2	Orphanet:363999	Non-immune hydrops fetalis

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
ANGPT2	HGNC:485	ENSG00000091879	O15123	Angiopoietin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANGPT2	Angiopoietin-2	Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANGPT2	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS

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
popliteal artery	1
tendon of biceps brachii	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANGPT2	219	broad	marker	tendon of biceps brachii, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANGPT2	2,065

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANGPT2	O15123	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Tie2 Signaling	1	601.0×	0.005	ANGPT2
Cell surface interactions at the vascular wall	1	95.2×	0.016	ANGPT2
Hemostasis	1	36.0×	0.028	ANGPT2

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
negative regulation of positive chemotaxis	1	16852.0×	0.001	ANGPT2
glomerulus vasculature development	1	4213.0×	0.002	ANGPT2
Tie signaling pathway	1	3370.4×	0.002	ANGPT2
positive regulation of coagulation	1	2808.7×	0.002	ANGPT2
negative regulation of cell-substrate adhesion	1	1053.2×	0.004	ANGPT2
maternal process involved in female pregnancy	1	936.2×	0.004	ANGPT2
negative regulation of blood vessel endothelial cell migration	1	732.7×	0.004	ANGPT2
animal organ regeneration	1	601.9×	0.004	ANGPT2
germ cell development	1	455.5×	0.005	ANGPT2
response to activity	1	324.1×	0.006	ANGPT2
cellular response to growth factor stimulus	1	318.0×	0.006	ANGPT2
response to mechanical stimulus	1	300.9×	0.006	ANGPT2
response to glucose	1	255.3×	0.006	ANGPT2
blood coagulation	1	173.7×	0.008	ANGPT2
negative regulation of angiogenesis	1	168.5×	0.008	ANGPT2
positive regulation of angiogenesis	1	115.4×	0.011	ANGPT2
response to hypoxia	1	95.8×	0.012	ANGPT2
gene expression	1	79.9×	0.014	ANGPT2
angiogenesis	1	62.4×	0.017	ANGPT2
signal transduction	1	16.1×	0.062	ANGPT2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
ANGPT2	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ANGPT2

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)
ANGPT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.