Bockenheimer syndrome

Summary

Bockenheimer syndrome (MONDO:0016311) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 21

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0001015	Prominent superficial veins	Very frequent (80-99%)
HP:0001528	Hemihypertrophy	Very frequent (80-99%)
HP:0006496	Aplasia/hypoplasia involving bones of the upper limbs	Very frequent (80-99%)
HP:0012721	Venous malformation	Very frequent (80-99%)
HP:0025104	Capillary malformation	Very frequent (80-99%)
HP:0040064	Abnormality of limbs	Very frequent (80-99%)
HP:0100555	Asymmetric growth	Very frequent (80-99%)
HP:0100585	Telangiectasia of the skin	Very frequent (80-99%)
HP:0000969	Edema	Frequent (30-79%)
HP:0002753	Thin bony cortex	Frequent (30-79%)
HP:0002984	Hypoplasia of the radius	Frequent (30-79%)
HP:0003022	Hypoplasia of the ulna	Frequent (30-79%)
HP:0004936	Venous thrombosis	Frequent (30-79%)
HP:0005792	Short humerus	Frequent (30-79%)
HP:0010484	Hypertrophy of the upper limb	Frequent (30-79%)
HP:0011804	Abnormal muscle physiology	Frequent (30-79%)
HP:0100671	Abnormal trabecular bone morphology	Frequent (30-79%)
HP:0001155	Abnormality of the hand	Occasional (5-29%)
HP:0001760	Abnormal foot morphology	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0009824	Upper limb undergrowth	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Bockenheimer syndrome
Mondo ID	MONDO:0016311
Orphanet	217008
ICD-11	1659229633
UMLS	C5679814
MedGen	1843091
GARD	0013063
Is cancer (heuristic)	no

Also known as: genuine diffuse phlebectasia

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › skin vascular disease › Bockenheimer syndrome

Related subtypes (19): Behcet disease, blue rubber bleb nevus, familial multiple nevi flammei, Sneddon syndrome, generalized essential telangiectasia, cutis marmorata telangiectatica congenita, angioedema, malignant atrophic papulosis, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, calciphylaxis cutis, cutaneous collagenous vasculopathy, Wyburn-Mason syndrome, Cobb syndrome, chilblain lupus, angioma serpiginosum, pityriasis lichenoides, livedo reticularis, atrophic papulosis

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
981229	NM_000459.5(TEK):c.2740C>T (p.Leu914Phe)	TEK	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TEK	Orphanet:1059	Blue rubber bleb nevus
TEK	Orphanet:2451	Mucocutaneous venous malformations
TEK	Orphanet:714806	Multifocal sporadic venous malformation
TEK	Orphanet:98976	Congenital glaucoma

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
TEK	HGNC:11724	ENSG00000120156	Q02763	Angiopoietin-1 receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TEK	Angiopoietin-1 receptor	Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskelet…

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)
TEK	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
diaphragm	1
right lung	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TEK	223	broad	marker	right lung, diaphragm, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TEK	2,762

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TEK	Q02763	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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×	0.012	TEK
MAPK1/MAPK3 signaling	1	131.3×	0.018	TEK
MAPK family signaling cascades	1	102.9×	0.018	TEK
Cell surface interactions at the vascular wall	1	95.2×	0.018	TEK
RAF/MAP kinase cascade	1	61.1×	0.023	TEK
Hemostasis	1	36.0×	0.032	TEK
Signal Transduction	1	10.2×	0.098	TEK

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
regulation of endothelial cell apoptotic process	1	8426.0×	0.002	TEK
glomerulus vasculature development	1	4213.0×	0.002	TEK
regulation of establishment or maintenance of cell polarity	1	3370.4×	0.002	TEK
Tie signaling pathway	1	3370.4×	0.002	TEK
regulation of vascular permeability	1	1123.5×	0.004	TEK
heart trabecula formation	1	1123.5×	0.004	TEK
definitive hemopoiesis	1	936.2×	0.004	TEK
positive regulation of Rac protein signal transduction	1	648.1×	0.004	TEK
positive regulation of focal adhesion assembly	1	648.1×	0.004	TEK
positive regulation of intracellular signal transduction	1	648.1×	0.004	TEK
positive regulation of Rho protein signal transduction	1	581.1×	0.004	TEK
endothelial cell proliferation	1	543.6×	0.004	TEK
negative regulation of endothelial cell apoptotic process	1	495.6×	0.004	TEK
sprouting angiogenesis	1	481.5×	0.004	TEK
substrate adhesion-dependent cell spreading	1	343.9×	0.006	TEK
positive regulation of endothelial cell migration	1	251.5×	0.007	TEK
positive regulation of endothelial cell proliferation	1	230.8×	0.008	TEK
cellular response to mechanical stimulus	1	216.1×	0.008	TEK
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.009	TEK
negative regulation of angiogenesis	1	168.5×	0.009	TEK
negative regulation of inflammatory response	1	137.0×	0.010	TEK
positive regulation of angiogenesis	1	115.4×	0.012	TEK
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.015	TEK
positive regulation of MAPK cascade	1	80.6×	0.015	TEK
heart development	1	78.8×	0.015	TEK
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.015	TEK
cell-cell signaling	1	69.6×	0.016	TEK
cell surface receptor signaling pathway	1	64.1×	0.017	TEK
angiogenesis	1	62.4×	0.017	TEK
negative regulation of apoptotic process	1	34.8×	0.029	TEK

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
TEK	CETIRIZINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TEK	46	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CETIRIZINE	4	TEK
FEDRATINIB	4	TEK
TIVOZANIB	4	TEK
AXITINIB	4	TEK
SORAFENIB	4	TEK
NICLOSAMIDE	4	TEK
AMPICILLIN	4	TEK
NERATINIB	4	TEK
INFIGRATINIB PHOSPHATE	4	TEK
INFIGRATINIB	4	TEK
REGORAFENIB	4	TEK
CABOZANTINIB	4	TEK
VANDETANIB	4	TEK
NILOTINIB	4	TEK
BOSUTINIB	4	TEK
PAZOPANIB	4	TEK
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
LINIFANIB	3	TEK
BRIVANIB	3	TEK
CEDIRANIB	3	TEK
LESTAURTINIB	3	TEK
DORAMAPIMOD	2	TEK
FORETINIB	2	TEK
REBASTINIB	2	TEK
CEP-11981	2	TEK
DEFOSBARASERTIB	2	TEK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TEK	707	Binding:701, Functional:4, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TEK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TEK	707

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)
CETIRIZINE	4	TEK
FEDRATINIB	4	TEK
TIVOZANIB	4	TEK
AXITINIB	4	TEK
SORAFENIB	4	TEK
NICLOSAMIDE	4	TEK
AMPICILLIN	4	TEK
NERATINIB	4	TEK
INFIGRATINIB PHOSPHATE	4	TEK
INFIGRATINIB	4	TEK
REGORAFENIB	4	TEK
CABOZANTINIB	4	TEK
VANDETANIB	4	TEK
NILOTINIB	4	TEK
BOSUTINIB	4	TEK
PAZOPANIB	4	TEK
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
LINIFANIB	3	TEK
BRIVANIB	3	TEK
CEDIRANIB	3	TEK
LESTAURTINIB	3	TEK
DORAMAPIMOD	2	TEK
FORETINIB	2	TEK
REBASTINIB	2	TEK
CEP-11981	2	TEK
DEFOSBARASERTIB	2	TEK

Druggability pyramid

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

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