Lymphatic malformation 14

Summary

Lymphatic malformation 14 (MONDO:0957954) is a disease with 1 cohort gene.

At a glance

• 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 14
Mondo ID	MONDO:0957954
OMIM	620602
UMLS	C5882718
MedGen	1851480
GARD	0026897
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › lymphatic malformation › lymphatic malformation 14

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 11, lymphatic malformation 12, lymphatic malformation 8, congenital primary lymphedema of Gordon, lymphatic malformation 13

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:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2637893	NM_182918.4(ERG):c.1388del (p.Asn463fs)	ERG	Pathogenic	no assertion criteria provided
2637894	NM_182918.4(ERG):c.671_672del (p.Thr224fs)	ERG	Pathogenic	no assertion criteria provided
2637921	NM_182918.4(ERG):c.543del (p.Ser182fs)	ERG	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · 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
ERG	Limited	Autosomal dominant	lymphatic malformation 14	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ERG	Orphanet:319	Skeletal Ewing sarcoma
ERG	Orphanet:370334	Extraskeletal Ewing sarcoma

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
ERG	HGNC:3446	ENSG00000157554	P11308	Transcriptional regulator ERG	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ERG	Transcriptional regulator ERG	Transcriptional regulator.

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)
ERG	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
descending thoracic aorta	1
tendon of biceps brachii	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ERG	247	broad	marker	tendon of biceps brachii, descending thoracic aorta, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERG	1,223

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ERG	P11308	8

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
protein phosphorylation	1	68.0×	0.074	ERG
cell differentiation	1	29.1×	0.084	ERG
signal transduction	1	16.1×	0.084	ERG
positive regulation of transcription by RNA polymerase II	1	14.9×	0.084	ERG
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ERG

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
ERG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ERG	14	Binding:10, Functional:3, ADMET:1

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	ERG

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)
ERG	14	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.