Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome

Summary

Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (MONDO:0011555) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 6

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0002974	Radioulnar synostosis	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0004859	Amegakaryocytic thrombocytopenia	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0001385	Hip dysplasia	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
Mondo ID	MONDO:0011555
MeSH	C565328
OMIM	605432
Orphanet	71289
SNOMED CT	721882001
UMLS	C1854273
MedGen	340183
GARD	0016687
Is cancer (heuristic)	no

Also known as: ATRUS syndrome · radioulnar synostosis with amegakaryocytic thrombocytopenia · RUSAT

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › congenital hematological disorder › radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome

Related subtypes (20): congenital anemia, congenital agammaglobulinemia, sulfhemoglobinemia, congenital, congenital factor XII deficiency, leukocyte adhesion deficiency type II, thrombocytopenia-absent radius syndrome, congenital thrombotic thrombocytopenic purpura, GNE myopathy, hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency, congenital factor XI deficiency, congenital plasminogen activator inhibitor type 1 deficiency, congenital analbuminemia, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, constitutional neutropenia, congenital vitamin K-dependent coagulation factors deficiency, congenital secondary polycythemia, hereditary thrombocytosis with transverse limb defect, congenital factor XIII deficiency, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, congenital amegakaryocytic thrombocytopenia 1

Subtypes (2): radioulnar synostosis with amegakaryocytic thrombocytopenia 2, radioulnar synostosis with amegakaryocytic thrombocytopenia 1

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · 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
MECOM	Definitive	Autosomal dominant	radioulnar synostosis with amegakaryocytic thrombocytopenia 2	6
HOXA11	Strong	Autosomal dominant	radioulnar synostosis with amegakaryocytic thrombocytopenia 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MECOM	Orphanet:402020	Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)
MECOM	Orphanet:71289	Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
HOXA11	Orphanet:71289	Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MECOM	HGNC:3498	ENSG00000085276	Q03112	Histone-lysine N-methyltransferase MECOM	gencc
HOXA11	HGNC:5101	ENSG00000005073	P31270	Homeobox protein Hox-A11	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MECOM	Histone-lysine N-methyltransferase MECOM	Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression.
HOXA11	Homeobox protein Hox-A11	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · 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
Transcription factor	2	8.3×	0.015

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MECOM	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
HOXA11	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardia of stomach	1
pylorus	1
renal medulla	1
body of uterus	1
endocervix	1
myometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MECOM	276	ubiquitous	marker	cardia of stomach, renal medulla, pylorus
HOXA11	98	broad	marker	body of uterus, myometrium, endocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MECOM	2,442
HOXA11	1,131

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MECOM	Q03112	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HOXA11	P31270	62.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Kidney development	1	407.9×	0.016	MECOM
Formation of the nephric duct	1	317.2×	0.016	MECOM
Formation of the ureteric bud	1	248.3×	0.016	HOXA11
PTEN Regulation	1	114.2×	0.025	MECOM
Regulation of PTEN gene transcription	1	89.2×	0.025	MECOM
PKMTs methylate histone lysines	1	80.4×	0.025	MECOM
Intracellular signaling by second messengers	1	45.7×	0.036	MECOM
Chromatin organization	1	40.8×	0.036	MECOM
Chromatin modifying enzymes	1	36.1×	0.036	MECOM
PIP3 activates AKT signaling	1	33.4×	0.036	MECOM
Developmental Biology	1	7.2×	0.146	MECOM
Signal Transduction	1	5.1×	0.187	MECOM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cell development	1	8426.0×	0.002	HOXA11
positive regulation of chondrocyte development	1	8426.0×	0.002	HOXA11
cartilage development involved in endochondral bone morphogenesis	1	1203.7×	0.007	HOXA11
mesodermal cell fate specification	1	1053.2×	0.007	HOXA11
embryonic skeletal joint morphogenesis	1	766.0×	0.007	HOXA11
prostate gland development	1	702.2×	0.007	HOXA11
heterochromatin organization	1	648.1×	0.007	MECOM
organ induction	1	601.9×	0.007	HOXA11
positive regulation of DNA-templated transcription	2	27.9×	0.007	MECOM, HOXA11
chondrocyte development	1	468.1×	0.007	HOXA11
positive regulation of chondrocyte differentiation	1	401.2×	0.007	HOXA11
uterus development	1	401.2×	0.007	HOXA11
negative regulation of programmed cell death	1	366.4×	0.007	MECOM
developmental growth	1	366.4×	0.007	HOXA11
proximal/distal pattern formation	1	324.1×	0.007	HOXA11
hematopoietic stem cell proliferation	1	324.1×	0.007	MECOM
negative regulation of JNK cascade	1	280.9×	0.008	MECOM
metanephros development	1	255.3×	0.008	HOXA11
embryonic forelimb morphogenesis	1	247.8×	0.008	HOXA11
response to testosterone	1	234.1×	0.008	HOXA11
dorsal/ventral pattern formation	1	210.7×	0.008	HOXA11
embryonic limb morphogenesis	1	200.6×	0.008	HOXA11
branching involved in ureteric bud morphogenesis	1	183.2×	0.009	HOXA11
response to estrogen	1	172.0×	0.009	HOXA11
embryonic digit morphogenesis	1	150.5×	0.010	HOXA11
regulation of transcription by RNA polymerase II	2	11.7×	0.010	MECOM, HOXA11
single fertilization	1	91.6×	0.015	HOXA11
anterior/posterior pattern specification	1	90.6×	0.015	HOXA11
methylation	1	85.1×	0.015	MECOM
protein maturation	1	81.8×	0.015	MECOM

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MECOM	0	0
HOXA11	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
MECOM	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	MECOM, HOXA11

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MECOM	1	—
HOXA11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.