Lymphatic malformation 8

Summary

Lymphatic malformation 8 (MONDO:0032907) 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 8
Mondo ID	MONDO:0032907
OMIM	618773
UMLS	C5231496
MedGen	1684767
GARD	0025772
Is cancer (heuristic)	no

Also known as: LMPHM8

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 8

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, 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 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
812514	NM_005795.6(CALCRL):c.611TAG[1] (p.Val205del)	CALCRL	Pathogenic	no assertion criteria provided
1192647	NM_005795.6(CALCRL):c.1128+34A>G	CALCRL	Benign	criteria provided, multiple submitters, no conflicts
1192648	NM_005795.6(CALCRL):c.782-58T>C	CALCRL	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
CALCRL	Limited	Unknown	lymphatic malformation 8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CALCRL	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
CALCRL	HGNC:16709	ENSG00000064989	Q16602	Calcitonin gene-related peptide type 1 receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CALCRL	Calcitonin gene-related peptide type 1 receptor	G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs).

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CALCRL	GPCR	yes		GPCR_2_secretin-like, GPCR_2_extracellular_dom, GPCR_2_calcitonin_rcpt_fam

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
right lung	1
upper lobe of left lung	1
upper lobe of lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CALCRL	227	ubiquitous	marker	right lung, upper lobe of left lung, upper lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CALCRL	1,168

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CALCRL	Q16602	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Calcitonin-like ligand receptors	1	1038.2×	0.011	CALCRL
Response of endothelial cells to shear stress	1	300.5×	0.014	CALCRL
Cellular responses to mechanical stimuli	1	259.6×	0.014	CALCRL
Class B/2 (Secretin family receptors)	1	190.3×	0.014	CALCRL
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	160.8×	0.014	CALCRL
G alpha (s) signalling events	1	73.2×	0.024	CALCRL
GPCR ligand binding	1	64.2×	0.024	CALCRL
GPCR downstream signalling	1	43.4×	0.031	CALCRL
Signaling by GPCR	1	40.1×	0.031	CALCRL
Cellular responses to stimuli	1	31.5×	0.035	CALCRL
Signal Transduction	1	10.2×	0.098	CALCRL

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
cellular response to sucrose stimulus	1	16852.0×	8e-04	CALCRL
adrenomedullin receptor signaling pathway	1	3370.4×	0.001	CALCRL
calcitonin gene-related peptide receptor signaling pathway	1	2808.7×	0.001	CALCRL
vascular associated smooth muscle cell proliferation	1	2808.7×	0.001	CALCRL
positive regulation of vascular associated smooth muscle cell proliferation	1	432.1×	0.006	CALCRL
receptor internalization	1	324.1×	0.006	CALCRL
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1	312.1×	0.006	CALCRL
calcium ion transport	1	181.2×	0.009	CALCRL
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.013	CALCRL
heart development	1	78.8×	0.017	CALCRL
cell surface receptor signaling pathway	1	64.1×	0.017	CALCRL
angiogenesis	1	62.4×	0.017	CALCRL
protein transport	1	43.9×	0.023	CALCRL

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
CALCRL	PRAMLINTIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CALCRL	12	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PRAMLINTIDE	4	CALCRL
UBROGEPANT	4	CALCRL
CALCITONIN SALMON	4	CALCRL
ATOGEPANT	4	CALCRL
RIMEGEPANT	4	CALCRL
ZAVEGEPANT	4	CALCRL
TELCAGEPANT	3	CALCRL
CAGRILINTIDE	3	CALCRL
MK3207	2	CALCRL
OLCEGEPANT	2	CALCRL
BI-44370	2	CALCRL
HTL-0022562	1	CALCRL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CALCRL	196	Binding:131, Functional:65

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CALCRL	196

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

12 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)
PRAMLINTIDE	4	CALCRL
UBROGEPANT	4	CALCRL
CALCITONIN SALMON	4	CALCRL
ATOGEPANT	4	CALCRL
RIMEGEPANT	4	CALCRL
ZAVEGEPANT	4	CALCRL
TELCAGEPANT	3	CALCRL
CAGRILINTIDE	3	CALCRL
MK3207	2	CALCRL
OLCEGEPANT	2	CALCRL
BI-44370	2	CALCRL
HTL-0022562	1	CALCRL

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CALCRL
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.