Scimitar syndrome

Summary

Scimitar syndrome (MONDO:0015987) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 39

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	2	Europe	Validated

Signs & symptoms

Clinical features (HPO)

39 HPO clinical features (Orphanet curated; top 39 by frequency):

HPO ID	Term	Frequency
HP:0001627	Abnormal heart morphology	Frequent (30-79%)
HP:0001629	Ventricular septal defect	Frequent (30-79%)
HP:0001631	Atrial septal defect	Frequent (30-79%)
HP:0001635	Congestive heart failure	Frequent (30-79%)
HP:0001651	Dextrocardia	Frequent (30-79%)
HP:0001680	Coarctation of aorta	Frequent (30-79%)
HP:0002088	Abnormal lung morphology	Frequent (30-79%)
HP:0002089	Pulmonary hypoplasia	Frequent (30-79%)
HP:0004971	Pulmonary artery hypoplasia	Frequent (30-79%)
HP:0005345	Abnormal vena cava morphology	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001719	Double outlet right ventricle	Occasional (5-29%)
HP:0001750	Single ventricle	Occasional (5-29%)
HP:0002092	Pulmonary arterial hypertension	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0002205	Recurrent respiratory infections	Occasional (5-29%)
HP:0004383	Hypoplastic left heart	Occasional (5-29%)
HP:0010772	Anomalous pulmonary venous return	Occasional (5-29%)
HP:0010773	Partial anomalous pulmonary venous return	Occasional (5-29%)
HP:0011560	Mitral atresia	Occasional (5-29%)
HP:0012382	Left-to-right shunt	Occasional (5-29%)
HP:0012735	Cough	Occasional (5-29%)
HP:0025495	Descending aorta hypoplasia	Occasional (5-29%)
HP:0040044	Hypoplasia of the diaphragm	Occasional (5-29%)
HP:0040045	Abnormal hemidiaphragm morphology	Occasional (5-29%)
HP:0100632	Pulmonary sequestration	Occasional (5-29%)
HP:0100730	Bronchogenic cyst	Occasional (5-29%)
HP:0100790	Hernia	Occasional (5-29%)
HP:0000119	Abnormality of the genitourinary system	Very rare (<1-4%)
HP:0000925	Abnormality of the vertebral column	Very rare (<1-4%)
HP:0001660	Truncus arteriosus	Very rare (<1-4%)
HP:0002107	Pneumothorax	Very rare (<1-4%)
HP:0011638	Anomalous origin of left coronary artery from the pulmonary artery	Very rare (<1-4%)
HP:0011662	Tricuspid atresia	Very rare (<1-4%)
HP:0011670	Left superior vena cava draining to coronary sinus	Very rare (<1-4%)
HP:0011671	Interrupted inferior vena cava with azygous continuation	Very rare (<1-4%)
HP:0012722	Heart block	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	scimitar syndrome
Mondo ID	MONDO:0015987
EFO	EFO:1001167
MeSH	D012587
Orphanet	185
ICD-11	1321054364
NCIT	C85056
SNOMED CT	39905002
UMLS	C0036400
MedGen	20675
GARD	0018680
MedDRA	10051951
Is cancer (heuristic)	no

Also known as: congenital pulmonary venolobar syndrome · Epibronchial right pulmonary vein syndrome · Halasz syndrome · hypogenetic lung syndrome

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › congenital pulmonary veins anomaly › congenital pulmonary venous return anomaly › scimitar syndrome

Related subtypes (2): congenital total pulmonary venous return anomaly, congenital partial pulmonary venous return anomaly

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1338864	NM_001127392.3(MYRF):c.1063C>T (p.Pro355Ser)	MYRF	Uncertain significance	criteria provided, single submitter
1338865	NM_001127392.3(MYRF):c.2201C>T (p.Ala734Val)	MYRF	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYRF	Orphanet:647811	Cardiac-urogenital syndrome

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
MYRF	HGNC:1181	ENSG00000124920	Q9Y2G1	Myelin regulatory factor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYRF	Myelin regulatory factor	Constitutes a precursor of the transcription factor.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYRF	Transcription factor	no		p53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2

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
C1 segment of cervical spinal cord	1
inferior vagus X ganglion	1
middle frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYRF	223	ubiquitous	marker	middle frontal gyrus, C1 segment of cervical spinal cord, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYRF	979

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYRF	Q9Y2G1	2

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
central nervous system myelin maintenance	1	2808.7×	0.002	MYRF
central nervous system myelination	1	991.3×	0.002	MYRF
positive regulation of myelination	1	766.0×	0.002	MYRF
response to immobilization stress	1	732.7×	0.002	MYRF
positive regulation of oligodendrocyte differentiation	1	674.1×	0.002	MYRF
protein autoprocessing	1	648.1×	0.002	MYRF
oligodendrocyte development	1	601.9×	0.002	MYRF
response to cocaine	1	581.1×	0.002	MYRF
oligodendrocyte differentiation	1	421.3×	0.003	MYRF
positive regulation of DNA-templated transcription	1	27.9×	0.036	MYRF

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYRF	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	MYRF

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)
MYRF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.