TARP syndrome

Summary

TARP syndrome (MONDO:0010711) is a disease caused by RBM10 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: RBM10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 34
• Phenotypes (HPO): 55

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

55 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000201	Pierre-Robin sequence	Very frequent (80-99%)
HP:0001631	Atrial septal defect	Very frequent (80-99%)
HP:0001762	Talipes equinovarus	Very frequent (80-99%)
HP:0005301	Persistent left superior vena cava	Very frequent (80-99%)
HP:0000162	Glossoptosis	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000340	Sloping forehead	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000961	Cyanosis	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001838	Rocker bottom foot	Frequent (30-79%)
HP:0009891	Underdeveloped supraorbital ridges	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000085	Horseshoe kidney	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000239	Large fontanelles	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000385	Small earlobe	Occasional (5-29%)
HP:0000395	Prominent antihelix	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000574	Thick eyebrow	Occasional (5-29%)
HP:0000954	Single transverse palmar crease	Occasional (5-29%)
HP:0001161	Hand polydactyly	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001273	Abnormal corpus callosum morphology	Occasional (5-29%)
HP:0001321	Cerebellar hypoplasia	Occasional (5-29%)
HP:0001978	Extramedullary hematopoiesis	Occasional (5-29%)
HP:0002104	Apnea	Occasional (5-29%)
HP:0002136	Broad-based gait	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0004492	Widely patent fontanelles and sutures	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0006434	Hypoplasia of proximal radius	Occasional (5-29%)
HP:0009738	Abnormality of the antihelix	Occasional (5-29%)
HP:0012745	Short palpebral fissure	Occasional (5-29%)
HP:0030084	Clinodactyly	Occasional (5-29%)
HP:0000358	Posteriorly rotated ears	Occasional (5-29%)
HP:0000199	Tongue nodules	Very rare (<1-4%)
HP:0000648	Optic atrophy	Very rare (<1-4%)
HP:0000767	Pectus excavatum	Very rare (<1-4%)
HP:0000879	Short sternum	Very rare (<1-4%)
HP:0001636	Tetralogy of Fallot	Very rare (<1-4%)
HP:0002089	Pulmonary hypoplasia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	TARP syndrome
Mondo ID	MONDO:0010711
MeSH	C536942
OMIM	311900
Orphanet	2886
DOID	DOID:0111780
SNOMED CT	725911008
UMLS	C1839463
MedGen	333324
GARD	0010089
Is cancer (heuristic)	no

Also known as: Pierre Robin sequence - congenital heart defect - talipes · Pierre Robin sequence-congenital heart defect-talipes syndrome · Pierre Robin syndrome - congenital heart defect - talipes · Pierre Robin syndrome-congenital heart defect-talipes syndrome · talipes equinovarus - atrial septal defect - Robin sequence - persistence of the left superior vena cava · talipes equinovarus-atrial septal defect-Robin sequence-persistence of the left superior vena cava syndrome · tarp syndrome · TARP syndrome, X-linked recessive · TARPS

Data availability: 34 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › cardiogenetic disease › TARP syndrome

Related subtypes (72): ventricular septal defect, hypoplastic left heart syndrome, familial cardiomyopathy, atrial septal defect, familial bicuspid aortic valve, Alagille syndrome, Holt-Oram syndrome, supravalvular aortic stenosis, tetralogy of fallot, DiGeorge syndrome, velocardiofacial syndrome, MGAT2-congenital disorder of glycosylation, dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome, heart defects-limb shortening syndrome, Sengers syndrome, CHARGE syndrome, Ehlers-Danlos syndrome, cardiac valvular type, Ellis-van Creveld syndrome, Larsen-like syndrome, B3GAT3 type, familial atrial myxoma, pericardial effusion, chronic, Peters plus syndrome, alveolar capillary dysplasia with misalignment of pulmonary veins, CHIME syndrome, cardiac valvular dysplasia, X-linked, Ehlers-Danlos syndrome, musculocontractural type, patent ductus arteriosus-bicuspid aortic valve-hand anomalies syndrome, postural orthostatic tachycardia syndrome, tricuspid atresia, patent ductus arteriosus, coronary artery disease, autosomal dominant, 1, coronary artery disease, autosomal dominant 2, COG1-congenital disorder of glycosylation, familial retinal arterial macroaneurysm, sinoatrial node dysfunction and deafness, congenital heart defects, multiple types, 3, congenital heart defects, multiple types, 2, 8q24.3 microdeletion syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome, transketolase deficiency, lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome, dextrocardia, LMNA-related cardiocutaneous progeria syndrome, dextro-looped transposition of the great arteries, familial atrioventricular septal defect, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, congenital vertebral-cardiac-renal anomalies syndrome, inherited mitral valve disease, Hordnes Engebretsen Knudtson syndrome, mehta lewis patton syndrome, congenital heart defects, multiple types, 5, structural congenital heart disease, multiple types - GATA4, congenital alveolar dysplasia due to FGF10, congenital alveolar dysplasia due to TBX4, GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes, RBFOX2-related congenital heart disorder, ACTN2-related cardiac and skeletal myopathy, ACTC1-related distal arthrogryposis with congenital heart disease, HAND1 related congenital heart defect, MYH-6 related congenital heart defects, HAND2 related congenital heart defect, congenital heart defects, multiple types, 8, with or without heterotaxy, congenital heart defects, multiple types, 9, cardiac conduction disease with or without cardiomyoopathy, fibromuscular dysplasia of the coronary arteries, TFAP2B-related congenital heart disease spectrum disorder, PLD1-related congenital heart disease, cardiogenetic rhythm disorder, TNNT2-related cardiomyopathy, NOTCH1-related AOS spectrum disorder

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

34 retrieved; paginated sample, class counts are floors:

13 pathogenic, 12 likely pathogenic, 5 uncertain significance, 2 likely benign, 1 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
11643	NM_005676.5(RBM10):c.1893dup (p.Pro632fs)	RBM10	Pathogenic	no assertion criteria provided
11644	NM_005676.5(RBM10):c.1235G>A (p.Trp412Ter)	RBM10	Pathogenic	no assertion criteria provided
1323521	NM_005676.5(RBM10):c.1722C>G (p.Tyr574Ter)	RBM10	Pathogenic	criteria provided, single submitter
137613	NM_005676.5(RBM10):c.448C>T (p.Gln150Ter)	RBM10	Pathogenic	no assertion criteria provided
1699224	NM_005676.5(RBM10):c.373G>T (p.Glu125Ter)	RBM10	Pathogenic	criteria provided, single submitter
1700155	NM_005676.5(RBM10):c.292C>T (p.Arg98Ter)	RBM10	Pathogenic	criteria provided, multiple submitters, no conflicts
1806104	NM_005676.5(RBM10):c.1993_1996del (p.Gln665fs)	RBM10	Pathogenic	criteria provided, single submitter
3254884	NM_005676.5(RBM10):c.579_586dup (p.Asn196fs)	RBM10	Pathogenic	criteria provided, single submitter
433146	NM_005676.5(RBM10):c.159del (p.Lys54fs)	RBM10	Pathogenic	criteria provided, single submitter
436516	NM_005676.5(RBM10):c.1249-1G>A	RBM10	Pathogenic	criteria provided, single submitter
625791	GRCh37/hg19 Xp11.23(chrX:47039376-47040521)	RBM10	Pathogenic	criteria provided, single submitter
689781	NM_005676.5(RBM10):c.724+2T>C	RBM10	Pathogenic	criteria provided, multiple submitters, no conflicts
977462	NM_005676.5(RBM10):c.1804_1805del (p.Ser602fs)	RBM10	Pathogenic	no assertion criteria provided
1333475	NM_005676.5(RBM10):c.2514C>G (p.Tyr838Ter)	RBM10	Likely pathogenic	criteria provided, single submitter
1697973	NM_005676.5(RBM10):c.2326C>T (p.Arg776Trp)	RBM10	Likely pathogenic	criteria provided, single submitter
1806258	NM_005676.5(RBM10):c.1974G>C (p.Trp658Cys)	RBM10	Likely pathogenic	criteria provided, single submitter
2429214	NM_005676.5(RBM10):c.331C>T (p.Gln111Ter)	RBM10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2671930	NM_005676.5(RBM10):c.2100+1G>A	RBM10	Likely pathogenic	criteria provided, single submitter
3899260	NM_005676.5:c.1594_2002delinsTGTTCTTCAAAATAGC	RBM10	Likely pathogenic	criteria provided, single submitter
4056417	NM_005676.5(RBM10):c.487C>T (p.Arg163Trp)	RBM10	Likely pathogenic	criteria provided, single submitter
4536615	NM_005676.5(RBM10):c.1861C>T (p.Gln621Ter)	RBM10	Likely pathogenic	criteria provided, single submitter
4819598	NM_005676.5(RBM10):c.94C>T (p.Arg32Ter)	RBM10	Likely pathogenic	criteria provided, single submitter
871200	NM_005676.5(RBM10):c.2296C>T (p.Arg766Cys)	RBM10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
976116	NM_005676.5(RBM10):c.396dup (p.Leu133fs)	RBM10	Likely pathogenic	criteria provided, single submitter
986344	NM_005676.5(RBM10):c.117_132del (p.Met39fs)	RBM10	Likely pathogenic	criteria provided, single submitter
1030008	NM_005676.5(RBM10):c.1476G>T (p.Ser492=)	RBM10	Uncertain significance	criteria provided, single submitter
2435380	NM_005676.5(RBM10):c.856G>A (p.Ala286Thr)	RBM10	Uncertain significance	criteria provided, single submitter
2435381	NM_005676.5(RBM10):c.995G>A (p.Arg332His)	RBM10	Uncertain significance	criteria provided, single submitter
4079850	NM_005676.5(RBM10):c.1444G>A (p.Ala482Thr)	RBM10	Uncertain significance	criteria provided, single submitter
4277458	NM_005676.5(RBM10):c.2248GAG[1] (p.Glu751del)	RBM10	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
RBM10	Definitive	X-linked	TARP syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RBM10	Orphanet:2886	TARP 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
RBM10	HGNC:9896	ENSG00000182872	P0DW28	Ribosome biogenesis inhibitor MINAS-60	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RBM10	Ribosome biogenesis inhibitor MINAS-60	Acts as a late-stage inhibitor of pre-60S ribosome assembly by preventing pre-60S ribosome export from nucleus.

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)
RBM10	Transcription factor	no		G_patch_dom, RRM_dom, Znf_RanBP2

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
cerebellar hemisphere	1
lower esophagus mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RBM10	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RBM10	24

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RBM10	P0DW28	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.012	RBM10
mRNA Polyadenylation	1	87.8×	0.016	RBM10
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.016	RBM10
mRNA Splicing - Major Pathway	1	54.6×	0.018	RBM10

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
vascular associated smooth muscle cell apoptotic process	1	16852.0×	3e-04	RBM10
negative regulation of ribosomal large subunit export from nucleus	1	16852.0×	3e-04	RBM10
vascular associated smooth muscle cell proliferation	1	2808.7×	0.001	RBM10
positive regulation of vascular associated smooth muscle cell apoptotic process	1	2106.5×	0.001	RBM10
negative regulation of mRNA splicing, via spliceosome	1	766.0×	0.002	RBM10
3’-UTR-mediated mRNA stabilization	1	702.2×	0.002	RBM10
negative regulation of vascular associated smooth muscle cell proliferation	1	674.1×	0.002	RBM10
mRNA splicing, via spliceosome	1	91.6×	0.012	RBM10
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	RBM10

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
RBM10	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	RBM10

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)
RBM10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.