Lymphatic malformation 11

Summary

Lymphatic malformation 11 (MONDO:0030316) is a disease caused by TIE1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TIE1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphatic malformation 11
Mondo ID	MONDO:0030316
OMIM	619401
UMLS	C5543614
MedGen	1784862
GARD	0025535
Is cancer (heuristic)	no

Also known as: LMPHM11 · lymphatic malformation 11

Data availability: 3 ClinVar variants · 3 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 11

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 10, lymphatic malformation 9, 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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1174133	NM_005424.5(TIE1):c.3326G>A (p.Arg1109His)	LOC126805720	Pathogenic	no assertion criteria provided
1174132	NM_005424.5(TIE1):c.1441C>T (p.Arg481Cys)	TIE1	Pathogenic	no assertion criteria provided
4080544	NM_005424.5(TIE1):c.2728C>T (p.Arg910Ter)	TIE1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
TIE1	Strong	Autosomal dominant	lymphatic malformation 11	3

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
TIE1	HGNC:11809	ENSG00000066056	P35590	Tyrosine-protein kinase receptor Tie-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TIE1	Tyrosine-protein kinase receptor Tie-1	Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TIE1	Kinase	yes	2.7.10.1	Prot_kinase_dom, EGF, Ser-Thr/Tyr_kinase_cat_dom

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
apex of heart	1
omental fat pad	1
peritoneum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TIE1	222	broad	marker	omental fat pad, peritoneum, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TIE1	1,358

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TIE1	P35590	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
branching involved in lymph vessel morphogenesis	1	16852.0×	0.001	TIE1
regulation of endothelial cell proliferation	1	4213.0×	0.001	TIE1
obsolete plasma membrane fusion	1	4213.0×	0.001	TIE1
regulation of extracellular matrix assembly	1	4213.0×	0.001	TIE1
lymphatic endothelial cell differentiation	1	2407.4×	0.001	TIE1
tissue remodeling	1	1296.3×	0.002	TIE1
mesoderm development	1	526.6×	0.005	TIE1
aortic valve morphogenesis	1	432.1×	0.005	TIE1
response to retinoic acid	1	383.0×	0.005	TIE1
vasculogenesis	1	255.3×	0.007	TIE1
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.008	TIE1
negative regulation of angiogenesis	1	168.5×	0.008	TIE1
positive regulation of angiogenesis	1	115.4×	0.011	TIE1
negative regulation of cell migration	1	111.6×	0.011	TIE1
in utero embryonic development	1	72.0×	0.016	TIE1
angiogenesis	1	62.4×	0.017	TIE1
signal transduction	1	16.1×	0.062	TIE1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
TIE1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TIE1	34	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	TIE1
AXITINIB	4	TIE1
SORAFENIB	4	TIE1
NERATINIB	4	TIE1
VANDETANIB	4	TIE1
NILOTINIB	4	TIE1
BOSUTINIB	4	TIE1
PAZOPANIB	4	TIE1
NINTEDANIB	4	TIE1
SUNITINIB	4	TIE1
ERLOTINIB	4	TIE1
QUIZARTINIB	4	TIE1
CRIZOTINIB	4	TIE1
MIDOSTAURIN	4	TIE1
LINIFANIB	3	TIE1
CANERTINIB	3	TIE1
BRIVANIB	3	TIE1
CEDIRANIB	3	TIE1
DOVITINIB	3	TIE1
LESTAURTINIB	3	TIE1
DORAMAPIMOD	2	TIE1
FORETINIB	2	TIE1
SU-014813	2	TIE1
DEFOSBARASERTIB	2	TIE1
R-406	2	TIE1
BIIB-091	2	TIE1
RAF-265	2	TIE1
TOZASERTIB	2	TIE1
BMS-754807	2	TIE1
PELITINIB	2	TIE1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TIE1	96	Binding:96

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TIE1	2.7.10.1	receptor protein-tyrosine kinase

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

30 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)
FEDRATINIB	4	TIE1
AXITINIB	4	TIE1
SORAFENIB	4	TIE1
NERATINIB	4	TIE1
VANDETANIB	4	TIE1
NILOTINIB	4	TIE1
BOSUTINIB	4	TIE1
PAZOPANIB	4	TIE1
NINTEDANIB	4	TIE1
SUNITINIB	4	TIE1
ERLOTINIB	4	TIE1
QUIZARTINIB	4	TIE1
CRIZOTINIB	4	TIE1
MIDOSTAURIN	4	TIE1
LINIFANIB	3	TIE1
CANERTINIB	3	TIE1
BRIVANIB	3	TIE1
CEDIRANIB	3	TIE1
DOVITINIB	3	TIE1
LESTAURTINIB	3	TIE1
DORAMAPIMOD	2	TIE1
FORETINIB	2	TIE1
SU-014813	2	TIE1
DEFOSBARASERTIB	2	TIE1
R-406	2	TIE1
BIIB-091	2	TIE1
RAF-265	2	TIE1
TOZASERTIB	2	TIE1
BMS-754807	2	TIE1
PELITINIB	2	TIE1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TIE1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.