Renpenning syndrome

Summary

Renpenning syndrome (MONDO:0010653) is a disease caused by PQBP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PQBP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 61
• Phenotypes (HPO): 42

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		64	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

42 HPO clinical features (Orphanet curated; top 42 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0003202	Skeletal muscle atrophy	Very frequent (80-99%)
HP:0003510	Severe short stature	Very frequent (80-99%)
HP:0004326	Cachexia	Very frequent (80-99%)
HP:0000047	Hypospadias	Frequent (30-79%)
HP:0000272	Malar flattening	Frequent (30-79%)
HP:0000274	Small face	Frequent (30-79%)
HP:0000275	Narrow face	Frequent (30-79%)
HP:0000276	Long face	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000303	Mandibular prognathia	Frequent (30-79%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000400	Macrotia	Frequent (30-79%)
HP:0000448	Prominent nose	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0000772	Abnormal rib morphology	Frequent (30-79%)
HP:0000912	Sprengel anomaly	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0008734	Decreased testicular size	Frequent (30-79%)
HP:0045074	Thin eyebrow	Frequent (30-79%)
HP:0100830	Round ear	Frequent (30-79%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0000819	Diabetes mellitus	Occasional (5-29%)
HP:0001172	Abnormal thumb morphology	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001387	Joint stiffness	Occasional (5-29%)
HP:0001572	Macrodontia	Occasional (5-29%)
HP:0002023	Anal atresia	Occasional (5-29%)
HP:0002705	High, narrow palate	Occasional (5-29%)
HP:0003328	Abnormal hair laboratory examination	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0008499	High hypermetropia	Occasional (5-29%)
HP:0010761	Broad columella	Occasional (5-29%)
HP:0030853	Heterotaxy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Renpenning syndrome
Mondo ID	MONDO:0010653
MeSH	C537761
OMIM	309500
Orphanet	3242
DOID	DOID:0060179
ICD-11	1415315699
NCIT	C165533
SNOMED CT	699669001
UMLS	C0796135
MedGen	208670
GARD	0009509
Is cancer (heuristic)	no

Also known as: Golabi-Ito-Hall syndrome · intellectual disability, X-linked Renpenning type · mental retardation, X-linked 55 · mental retardation, X-linked Renpenning type · mental retardation, X-linked, Renpenning type · mental retardation, X-linked, syndromic 3 · mental retardation, X-linked, syndromic 8 · mental retardation, X-linked, with spastic diplegia · MRXS3 · MRXS8 · Renpenning syndrome · Renpenning syndrome 1 · Renpenning syndrome type 1 · renpenning syndrome, X-linked recessive · RENS1 · Sutherland-Haan syndrome · Sutherland-Haan X-linked intellectual disability syndrome · Sutherland-Haan X-linked mental retardation syndrome · syndromic X-linked intellectual disability 8 · X-linked intellectual disability due to PQBP1 mutations (+5 more)

Data availability: 61 ClinVar variants · 4 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › X-linked syndromic intellectual disability › Renpenning syndrome

Related subtypes (80): X-linked intellectual disability-psychosis-macroorchidism syndrome, X-linked intellectual disability-plagiocephaly syndrome, intellectual disability, X-linked 49, MEHMO syndrome, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability, Stocco dos Santos type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, X-linked intellectual disability-cerebellar hypoplasia syndrome, Allan-Herndon-Dudley syndrome, syndromic X-linked intellectual disability Claes-Jensen type, X-linked intellectual disability-retinitis pigmentosa syndrome, syndromic X-linked intellectual disability 14, syndromic X-linked intellectual disability 94, intellectual disability, X-linked syndromic, Turner type, syndromic X-linked intellectual disability Shrimpton type, X-linked intellectual disability-craniofacioskeletal syndrome, syndromic X-linked intellectual disability Raymond type, syndromic X-linked intellectual disability 17, syndromic X-linked intellectual disability Nascimento type, syndromic X-linked intellectual disability Chudley-Schwartz type, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome, X-linked intellectual disability, Cantagrel type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked, syndromic, Bain type, Borjeson-Forssman-Lehmann syndrome, Coffin-Lowry syndrome, syndromic X-linked intellectual disability 5, X-linked intellectual disability-seizures-psoriasis syndrome, Partington syndrome, syndromic X-linked intellectual disability 12, severe X-linked intellectual disability, Gustavson type, syndromic X-linked intellectual disability Snyder type, Wilson-Turner syndrome, Prieto syndrome, skeletal dysplasia-intellectual disability syndrome, X-linked intellectual disability-spastic quadriparesis syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked intellectual disability, Schimke type, X-linked intellectual disability, Cilliers type, X-linked intellectual disability, van Esch type, X-linked intellectual disability-epilepsy syndrome, ATR-X-related syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, X-linked intellectual disability, Schutz type, X-linked intellectual disability-hypotonia-movement disorder syndrome, X-linked intellectual disability with isolated growth hormone deficiency, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-precocious puberty-obesity syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability-macrocephaly-macroorchidism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Seemanova type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, X-linked intellectual disability-acromegaly-hyperactivity syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, fried syndrome, X-linked intellectual disability-ataxia-apraxia syndrome, intellectual developmental disorder, X-linked, syndromic, Pilorge type, Paganini-Miozzo syndrome, intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type, intellectual disability, X-linked, syndromic, 35, intellectual disability, X-linked, syndromic, Houge type, MED12-related intellectual disability syndrome, NAA10-related syndrome, ATP6AP2-related disorder, X-linked intellectual disability with hypopituitarism, SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder, intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, intellectual developmental disorder, X-linked, syndromic 37, CASK-related intellectual disability

Subtypes (4): X-linked intellectual disability, Porteous type, hamel cerebro-palato-cardiac syndrome, X-linked intellectual disability, Golabi-Ito-hall type, X-linked intellectual disability, Sutherland-Haan type

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

61 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 15 pathogenic, 7 likely pathogenic, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 4 benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10979	NM_001032382.2(PQBP1):c.461_462dup (p.Arg155fs)	PQBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
10980	NM_001032382.2(PQBP1):c.459_462del (p.Arg153fs)	PQBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10981	NM_001032382.2(PQBP1):c.461_462del (p.Glu154fs)	PQBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
10982	NM_001032382.2(PQBP1):c.640dup (p.Arg214fs)	PQBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
10983	NM_001032382.2(PQBP1):c.547_569del (p.Glu183fs)	PQBP1	Pathogenic	no assertion criteria provided
10985	NM_001032382.2(PQBP1):c.194A>G (p.Tyr65Cys)	PQBP1	Pathogenic	criteria provided, single submitter
1517778	NM_001032382.2(PQBP1):c.292+1G>A	PQBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1684266	NM_001032382.2(PQBP1):c.175_178del (p.Ser59fs)	PQBP1	Pathogenic	criteria provided, single submitter
1691229	NM_001032382.2(PQBP1):c.575_576del (p.Lys192fs)	PQBP1	Pathogenic	criteria provided, single submitter
2663820	NM_001032382.2(PQBP1):c.457_459del (p.Arg153del)	PQBP1	Pathogenic	criteria provided, single submitter
3220899	NM_001032382.2(PQBP1):c.376_377del (p.Arg126fs)	PQBP1	Pathogenic	criteria provided, single submitter
3764089	NM_001032382.2(PQBP1):c.424del (p.Arg142fs)	PQBP1	Pathogenic	no assertion criteria provided
3897861	NM_001032382.2(PQBP1):c.641+1dup	PQBP1	Pathogenic	criteria provided, single submitter
4795963	NM_001032382.2(PQBP1):c.559del (p.Tyr187fs)	PQBP1	Pathogenic	criteria provided, single submitter
4795964	NM_001032382.2(PQBP1):c.632dup (p.Asp211fs)	PQBP1	Pathogenic	criteria provided, single submitter
4795965	NM_001032382.2:c.641_642insC	PQBP1	Pathogenic	criteria provided, single submitter
545093	NM_001032382.2(PQBP1):c.586C>T (p.Arg196Ter)	PQBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807471	NM_001032382.2(PQBP1):c.599_600del (p.Glu200fs)	PQBP1	Pathogenic	criteria provided, single submitter
4795962	NM_001032382.2(PQBP1):c.28C>G (p.Arg10Gly)	LOC130068256	Likely pathogenic	criteria provided, single submitter
1030959	NM_001032382.2(PQBP1):c.32T>C (p.Leu11Ser)	PQBP1	Likely pathogenic	criteria provided, single submitter
1802539	NM_001032382.2(PQBP1):c.233C>A (p.Pro78Gln)	PQBP1	Likely pathogenic	criteria provided, single submitter
2443062	NM_001032382.2(PQBP1):c.721del (p.Gln241fs)	PQBP1	Likely pathogenic	criteria provided, single submitter
816841	NM_001032382.2(PQBP1):c.463C>T (p.Arg155Ter)	PQBP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
931434	NM_001032382.2(PQBP1):c.623C>A (p.Ser208Ter)	PQBP1	Likely pathogenic	criteria provided, single submitter
977914	NM_001032382.2(PQBP1):c.727C>T (p.Arg243Trp)	PQBP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1527945	NM_001032382.2(PQBP1):c.530G>A (p.Arg177His)	PQBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
235848	NM_001032382.2(PQBP1):c.731C>T (p.Pro244Leu)	PQBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
547755	NM_001032382.2(PQBP1):c.397C>T (p.Arg133Trp)	PQBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
561092	NM_001032382.2(PQBP1):c.541C>T (p.Arg181Trp)	PQBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
912839	NM_001032382.2(PQBP1):c.642-9C>A	PQBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · 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
PQBP1	Definitive	X-linked	Renpenning syndrome	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PQBP1	Orphanet:93945	X-linked intellectual disability, Porteous type
PQBP1	Orphanet:93946	Hamel cerebro-palato-cardiac syndrome
PQBP1	Orphanet:93947	X-linked intellectual disability, Golabi-Ito-Hall type
PQBP1	Orphanet:93950	X-linked intellectual disability, Sutherland-Haan type

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
PQBP1	HGNC:9330	ENSG00000102103	O60828	Polyglutamine-binding protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PQBP1	Polyglutamine-binding protein 1	Intrinsically disordered protein that acts as a scaffold, and which is involved in different processes, such as pre-mRNA splicing, transcription regulation, innate immunity and neuron development.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PQBP1	Scaffold/PPI	no		WW_dom, WW_dom_sf

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
left ovary	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PQBP1	292	ubiquitous	marker	left ovary, right ovary, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PQBP1	1,556

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PQBP1	O60828	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
mRNA Splicing - Major Pathway	1	54.6×	0.022	PQBP1
Dengue Virus-Host Interactions	1	45.7×	0.022	PQBP1

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 exogenous dsRNA	1	1053.2×	0.004	PQBP1
regulation of dendrite morphogenesis	1	732.7×	0.004	PQBP1
alternative mRNA splicing, via spliceosome	1	674.1×	0.004	PQBP1
positive regulation of defense response to virus by host	1	526.6×	0.004	PQBP1
activation of innate immune response	1	481.5×	0.004	PQBP1
positive regulation of type I interferon production	1	421.3×	0.004	PQBP1
regulation of RNA splicing	1	218.9×	0.007	PQBP1
neuron projection development	1	122.1×	0.011	PQBP1
defense response to virus	1	69.3×	0.018	PQBP1
innate immune response	1	33.6×	0.032	PQBP1
regulation of DNA-templated transcription	1	31.6×	0.032	PQBP1

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
PQBP1	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	PQBP1

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)
PQBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.