PQBP1

Summary

PQBP1 (polyglutamine binding protein 1, HGNC:9330) is a protein-coding gene on chromosome Xp11.23, encoding Polyglutamine-binding protein 1 (O60828). 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. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 10084 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Renpenning syndrome (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 217 total — 19 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 75
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001032382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9330
Approved symbol	PQBP1
Name	polyglutamine binding protein 1
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000102103
Ensembl biotype	protein_coding
OMIM	300463
Entrez	10084

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 19 protein_coding, 6 retained_intron, 4 nonsense_mediated_decay

ENST00000218224, ENST00000247140, ENST00000376563, ENST00000376566, ENST00000396763, ENST00000443648, ENST00000447146, ENST00000456306, ENST00000463529, ENST00000465859, ENST00000470059, ENST00000470062, ENST00000472742, ENST00000473764, ENST00000474671, ENST00000477997, ENST00000486150, ENST00000651767, ENST00000692023, ENST00000875808, ENST00000875809, ENST00000875810, ENST00000875811, ENST00000875812, ENST00000875813, ENST00000920021, ENST00000920022, ENST00000920023, ENST00000965909

RefSeq mRNA: 9 — MANE Select: NM_001032382 NM_001032381, NM_001032382, NM_001032383, NM_001032384, NM_001167989, NM_001167990, NM_001167992, NM_005710, NM_144495

CCDS: CCDS14309, CCDS55412

Canonical transcript exons

ENST00000447146 — 7 exons

Exon	Start	End
ENSE00001151029	48902928	48903143
ENSE00001414283	48897930	48898082
ENSE00003460495	48902732	48902795
ENSE00003505535	48901930	48902042
ENSE00003507515	48902233	48902517
ENSE00003538715	48901190	48901301
ENSE00003540214	48898492	48898576

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.1550 / max 249.2336, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196300	42.5298	1820
196299	3.1951	1556
196301	0.4301	155

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	97.09	gold quality
right ovary	UBERON:0002118	96.94	gold quality
cerebellar hemisphere	UBERON:0002245	96.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.89	gold quality
cerebellar cortex	UBERON:0002129	96.85	gold quality
granulocyte	CL:0000094	96.84	gold quality
body of pancreas	UBERON:0001150	96.78	gold quality
adenohypophysis	UBERON:0002196	96.78	gold quality
monocyte	CL:0000576	96.68	gold quality
cortical plate	UBERON:0005343	96.54	gold quality
body of stomach	UBERON:0001161	96.51	gold quality
tendon of biceps brachii	UBERON:0008188	96.50	gold quality
apex of heart	UBERON:0002098	96.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.38	gold quality
mucosa of stomach	UBERON:0001199	96.27	gold quality
mononuclear cell	CL:0000842	96.25	gold quality
endocervix	UBERON:0000458	96.23	gold quality
leukocyte	CL:0000738	96.16	gold quality
body of uterus	UBERON:0009853	96.14	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.10	gold quality
cerebellum	UBERON:0002037	96.08	gold quality
islet of Langerhans	UBERON:0000006	96.06	gold quality
skin of abdomen	UBERON:0001416	96.04	gold quality
left uterine tube	UBERON:0001303	96.00	gold quality
ganglionic eminence	UBERON:0004023	96.00	gold quality
pituitary gland	UBERON:0000007	95.99	gold quality
left adrenal gland cortex	UBERON:0035825	95.96	gold quality
skin of leg	UBERON:0001511	95.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.89	gold quality
right adrenal gland cortex	UBERON:0035827	95.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	567.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SOX2

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 37)

• Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation (PMID:14634649)
• mutations cause Renpenning syndrome and X-linked mental retardation with microcephaly (PMID:15024694)
• Mutations in the polyglutamine-binding protein 1 gene is associated with X-linked mental retardation (PMID:15355434)
• dysfunction of PQBP-1 induces mitochondrial stress, a key molecular pathomechanism that is shared among human neurodegenerative disorders (PMID:16104847)
• Pathogenic frameshift mutations in PQBP1 are rare in mentally retarded patients lacking specific associated signs; the 21 bp in-frame deletions may be non-pathogenic, or alternatively could act subtly on PQBP1 function. (PMID:16493439)
• Data suggest that the SIPP1-PQBP1-induced nuclear inclusions are distinct from the protein aggregates that are associated with polyglutamine diseases and represent dynamic nucleoplasmic heteropolymers of SIPP1 and PQBP1. (PMID:18599155)
• Results suggest that pqbp-1.1 is involved in lipid metabolism of intestinal cells, and that dysfunction of lipid metabolism might underlie lean body, one of the most frequent symptoms associating with PQBP1-linked mental retrdation patients. (PMID:19119319)
• An evaluation of X-linked mental retardation (XLMR) pathology of PQBP1 mutations demonstrated nonsense-mediated mRNA decay and enhance exclusion of the mutant exon. (PMID:19847789)
• frameshift mutations in the PQBP-1 gene lead to expression of mutants lacking the ability to interact with U5-15kD (PMID:20307692)
• Y65C missense mutation in the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1 affects its binding activity and deregulates pre-mRNA splicing (PMID:20410308)
• mutations in PQBP1 caused variable loss of cell adhesion from impaired vesicle trafficking disrupts the neuroepithelial lining or neuronal migration and underlies periventricular heterotopia formation (PMID:20886605)
• Whole gene duplication of the PQBP1 gene in syndrome resembling Renpenning. (PMID:21204222)
• Evidence for a functional involvement of the four mutations affecting ATRX (p.1761M4T), PQBP1 (p.155R4X), and SLC6A8 (p.390P4L and p.477S4L), in the etiology of intellectual disability. (PMID:21267006)
• Data show that the PQBP1 mutation was found in 3 brothers with a phenotype comprising MR, short stature, lean body and microcephaly. (PMID:21315190)
• These data demonstrate a role for PQBP1 in the modulation of stress granules. (PMID:21933836)
• The results of this study addressed that the relationship between gene dose and phenotype relationship of dPQBP1 and investigated the mechanism responsible for the lifespan shortening’ (PMID:22901698)
• Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5-15 kD. (PMID:24781215)
• Study found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. (PMID:26046437)
• Results from a study on gene expression variability markers in early-stage human embryos shows that PQBP1 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• results suggest that the interaction between PQBP1 and WBP11 negatively modulates the U5-15kD binding of PQBP1 by an allosteric mechanism (PMID:27314904)
• The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing (PMID:27456546)
• Our data strongly support a gain-of-function pathogenic mechanism of PQBP1 c.459_462delAGAG and c.463_464dupAG mutations, and suggest that therapeutic strategies to restore FMRP function may be beneficial for those patients (PMID:28073926)
• PQBP1 inhibits IFI16/cGAS-induced signaling in response to cytosolic DNA. (PMID:29807326)
• This report expands the phenotypic spectrum of PQBP1-related disorders and is the second reported missense PQBP1 variant. (PMID:30244542)
• We studied the binding of PQBP-1 variants to the labelled peptide which is phosphorylated at positions 2 and 5 (YpSPTpSPS) and found that this interaction is significantly weakened in the two mutants. (PMID:30951824)
• X-linked hemizygous truncating mutation in PQBP1 gene is associated with Microphthalmos-anophthalmos-coloboma spectrum in Renpenning syndrome. (PMID:31718390)
• Renpenning syndrome in an Indian patient. (PMID:31840915)
• Renpenning syndrome in a female. (PMID:31840929)
• Frequency and distribution of polyQ disease intermediate-length repeat alleles in healthy Italian population. (PMID:31940111)
• The Renpenning syndrome-associated protein PQBP1 facilitates the nuclear import of splicing factor TXNL4A through the karyopherin beta2 receptor. (PMID:32041777)
• PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation. (PMID:33662272)
• Fatal Attraction: The Case of Toxic Soluble Dimers of Truncated PQBP-1 Mutants in X-Linked Intellectual Disability. (PMID:33668121)
• Novel regulation of the eEF2K/eEF2 pathway: prospects of ‘PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation’. (PMID:33734395)
• Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation. (PMID:34782623)
• PQBP1: The Key to Intellectual Disability, Neurodegenerative Diseases, and Innate Immunity. (PMID:35682906)
• The role of PQBP1 in neural development and function. (PMID:36815699)
• Splicing Factor PQBP1 Curtails BAX Expression to Promote Ovarian Cancer Progression. (PMID:38342602)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pqbp1	ENSDARG00000029724
mus_musculus	Pqbp1	ENSMUSG00000031157
rattus_norvegicus	Pqbp1	ENSRNOG00000007766
caenorhabditis_elegans		WBGENE00020647

Paralogs (2): CACTIN (ENSG00000105298), MARVELD3 (ENSG00000140832)

Protein

Protein identifiers

Polyglutamine-binding protein 1 — O60828 (reviewed: O60828)

Alternative names: 38 kDa nuclear protein containing a WW domain, Polyglutamine tract-binding protein 1

All UniProt accessions (4): O60828, A0A0S2Z4V5, A0A5H1ZRR1, H7C053

UniProt curated annotations — full annotation on UniProt →

Function. 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. Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species. May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery. May be involved in ATXN1 mutant-induced cell death. The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit. Involved in the assembly of cytoplasmic stress granule, possibly by participating in the transport of neuronal RNA granules. Also acts as an innate immune sensor of infection by retroviruses, such as HIV, by detecting the presence of reverse-transcribed DNA in the cytosol. Directly binds retroviral reverse-transcribed DNA in the cytosol and interacts with CGAS, leading to activate the cGAS-STING signaling pathway, triggering type-I interferon production.

Subunit / interactions. Interacts with POU3F2/Brn-2, ATXN1, TXNL4A, HTT and AR. Interaction with ATXN1 correlates positively with the length of the polyglutamine tract. Interacts with RNA polymerase II large subunit in a phosphorylation-dependent manner. Forms a ternary complex with ATXN1 mutant and phosphorylated RNA polymerase II. Interacts (via C-terminus) with TXNL4A and CD2BP2. Interacts (via WW domain) with ATN1 and SF3B1, and may interact with additional splice factors. Interacts (via WW domain) with WBP11; Leading to reduce interaction between PQBP1 and TXNL4A. Interacts with CAPRIN1. Interacts with DDX1. Interacts with SFPQ. Interacts with KHSRP.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasmic granule.

Tissue specificity. Widely expressed with high level in heart, skeletal muscle, pancreas, spleen, thymus, prostate, ovary, small intestine and peripheral blood leukocytes.

Disease relevance. Renpenning syndrome 1 (RENS1) [MIM:309500] An X-linked syndrome characterized by intellectual disability, microcephaly, short stature, and small testes. The craniofacies tends to be narrow and tall with upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WW domain may play a role as a transcriptional activator directly or via association with the transcription machinery. The WW domain mediates interaction with WBP11, ATN1, SF3B1 and the C-terminal domain of the RNA polymerase II large subunit. Except for the WW domain, the protein is intrinsically disordered.

Isoforms (10)

UniProt ID	Names	Canonical?
O60828-1	1, PQBP-1	yes
O60828-2	2
O60828-3	3, PQBP-1b/c
O60828-4	4, PQBP-1d
O60828-5	5
O60828-6	6
O60828-7	7
O60828-8	8, PQBP-1a
O60828-9	9
O60828-10	10

RefSeq proteins (9): NP_001027553, NP_001027554, NP_001027555, NP_001027556, NP_001161461, NP_001161462, NP_001161464, NP_005701, NP_652766 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR036020	WW_dom_sf	Homologous_superfamily

UniProt features (64 total): repeat 15, splice variant 15, mutagenesis site 12, sequence conflict 7, region of interest 5, sequence variant 3, modified residue 2, initiator methionine 1, chain 1, domain 1, compositionally biased region 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4BWQ	X-RAY DIFFRACTION	2.1
4BWS	X-RAY DIFFRACTION	2.5
4CDO	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60828-F1	70.44	0.08

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 94, 247

Mutagenesis-validated functional residues (12):

Position	Phenotype
52	enhances transcriptional activation. reduces transcriptional activation; when associated with a-75. markedly reduced tra
64	no effect on transcriptional activation; when associated with a-65 and a-66. markedly reduced transcriptional activation
65	no effect on transcriptional activation; when associated with a-64 and a-66. markedly reduced transcriptional activation
66	no effect on transcriptional activation; when associated with a-64 and a-65. markedly reduced transcriptional activation
75	no effect on transcriptional activation. reduces transcriptional activation; when associated with a-52. abolishes transc
78	no effect on transcriptional activation.
245	abolishes interaction with txnl4a.
248	abolishes interaction with txnl4a.
251	abolishes interaction with txnl4a.
252	abolishes interaction with txnl4a.
253	strongly reduces affinity for txnl4a.
255	strongly reduces affinity for txnl4a.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 344 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GALE_APL_WITH_FLT3_MUTATED_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (15): alternative mRNA splicing, via spliceosome (GO:0000380), activation of innate immune response (GO:0002218), positive regulation of defense response to virus by host (GO:0002230), regulation of DNA-templated transcription (GO:0006355), neuron projection development (GO:0031175), positive regulation of type I interferon production (GO:0032481), regulation of RNA splicing (GO:0043484), innate immune response (GO:0045087), regulation of dendrite morphogenesis (GO:0048814), defense response to virus (GO:0051607), cellular response to exogenous dsRNA (GO:0071360), immune system process (GO:0002376), mRNA processing (GO:0006397), RNA splicing (GO:0008380), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (5): DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), transcription coactivator activity (GO:0003713), ribonucleoprotein complex binding (GO:0043021), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929), cytoplasmic stress granule (GO:0010494), microtubule cytoskeleton (GO:0015630), nuclear body (GO:0016604), nuclear speck (GO:0016607), ciliary basal body (GO:0036064), neuronal ribonucleoprotein granule (GO:0071598), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
regulation of gene expression	2
RNA processing	2
cytoplasmic ribonucleoprotein granule	2
mRNA splicing, via spliceosome	1
activation of immune response	1
positive regulation of innate immune response	1
regulation of defense response to virus by host	1
regulation of RNA biosynthetic process	1
neuron development	1
plasma membrane bounded cell projection organization	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
RNA splicing	1
regulation of primary metabolic process	1
immune response	1
defense response to symbiont	1
regulation of anatomical structure morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite development	1
defense response	1
response to virus	1
response to exogenous dsRNA	1
cellular response to dsRNA	1
biological_process	1
mRNA metabolic process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
DNA binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
protein-containing complex binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PQBP1	ATXN1	P54253	925
PQBP1	TXNL4A	P83876	858
PQBP1	FTSJ1	Q9UET6	831
PQBP1	WBP11	Q9Y2W2	826
PQBP1	CGAS	Q8N884	765
PQBP1	POU3F2	P20265	742
PQBP1	HTT	P42858	697
PQBP1	HEXIM1	O94992	688
PQBP1	ATXN1L	P0C7T5	688
PQBP1	ZNF41	P51814	684
PQBP1	RBM17	Q96I25	638
PQBP1	WBP4	O75554	582
PQBP1	ATXN2	Q99700	569
PQBP1	UBQLN4	Q9NRR5	567
PQBP1	DDX41	Q9UJV9	543

IntAct

79 interactions, top by confidence:

A	B	Type	Score
WBP11	PQBP1	psi-mi:“MI:0915”(physical association)	0.800
PQBP1	WBP11	psi-mi:“MI:0407”(direct interaction)	0.800
WBP11	PQBP1	psi-mi:“MI:0914”(association)	0.800
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
GOLGA2	PQBP1	psi-mi:“MI:0915”(physical association)	0.720
PQBP1	LZTS2	psi-mi:“MI:0915”(physical association)	0.720
MAPRE1	PQBP1	psi-mi:“MI:0915”(physical association)	0.720
PQBP1	MAPRE1	psi-mi:“MI:0915”(physical association)	0.720
LZTS2	PQBP1	psi-mi:“MI:0915”(physical association)	0.720
PQBP1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
UBL5	SART1	psi-mi:“MI:0914”(association)	0.670
PQBP1	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (145): PQBP1 (Two-hybrid), MAPRE1 (Two-hybrid), LZTS2 (Two-hybrid), PQBP1 (Affinity Capture-MS), PQBP1 (Reconstituted Complex), PQBP1 (Co-fractionation), PQBP1 (Proximity Label-MS), PQBP1 (Affinity Capture-MS), PQBP1 (Affinity Capture-MS), PQBP1 (Affinity Capture-MS), PQBP1 (Affinity Capture-MS), PQBP1 (Affinity Capture-MS), PQBP1 (Affinity Capture-MS), TXNL4A (Two-hybrid), WBP11 (Two-hybrid)

ESM2 similar proteins: A1YFA7, A2T806, B0BN49, E1BB52, E9Q5K9, F1Q8W0, F4I2J8, F4JCU0, O60828, O74418, P0C196, P0CO16, P0CO17, P30651, P97868, Q10B98, Q14004, Q2HJC9, Q3KPW4, Q4IL82, Q4KLN7, Q4P4G8, Q4PB36, Q4PGL2, Q4V8I5, Q502P0, Q5AQ12, Q5F4A9, Q5RAA7, Q5U317, Q5XJD3, Q62504, Q66PJ3, Q6AXY7, Q6C1V6, Q6CEK8, Q6PCT5, Q6UN15, Q7Z6E9, Q80SY5

Diamond homologs: A1YFA7, A2T806, O60828, Q2HJC9, Q6PCT5, Q91VJ5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Polyadenylation	13	27.2×	8e-14
mRNA Splicing	10	26.1×	2e-10
Processing of Capped Intron-Containing Pre-mRNA	12	23.5×	5e-12
mRNA Splicing - Major Pathway	16	20.8×	3e-15
CHD1 and CHD2 subfamily	6	15.5×	9e-05
Metabolism of RNA	12	11.9×	1e-08
Dengue Virus-Host Interactions	10	10.9×	8e-07

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	12	22.9×	4e-11
mRNA processing	8	13.1×	3e-05
RNA splicing	6	11.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

217 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	11
Uncertain significance	94
Likely benign	31
Benign	8

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
10979	NM_001032382.2(PQBP1):c.461_462dup (p.Arg155fs)	Pathogenic
10981	NM_001032382.2(PQBP1):c.461_462del (p.Glu154fs)	Pathogenic
10982	NM_001032382.2(PQBP1):c.640dup (p.Arg214fs)	Pathogenic
10983	NM_001032382.2(PQBP1):c.547_569del (p.Glu183fs)	Pathogenic
10985	NM_001032382.2(PQBP1):c.194A>G (p.Tyr65Cys)	Pathogenic
1176932	NM_001032382.2(PQBP1):c.424C>T (p.Arg142Ter)	Pathogenic
1684266	NM_001032382.2(PQBP1):c.175_178del (p.Ser59fs)	Pathogenic
1691229	NM_001032382.2(PQBP1):c.575_576del (p.Lys192fs)	Pathogenic
2663820	NM_001032382.2(PQBP1):c.457_459del (p.Arg153del)	Pathogenic
2706546	NM_001032382.2(PQBP1):c.627C>A (p.Tyr209Ter)	Pathogenic
3220899	NM_001032382.2(PQBP1):c.376_377del (p.Arg126fs)	Pathogenic
3764089	NM_001032382.2(PQBP1):c.424del (p.Arg142fs)	Pathogenic
3897861	NM_001032382.2(PQBP1):c.641+1dup	Pathogenic
424138	NM_001032382.2(PQBP1):c.641+1G>A	Pathogenic
4795963	NM_001032382.2(PQBP1):c.559del (p.Tyr187fs)	Pathogenic
4795964	NM_001032382.2(PQBP1):c.632dup (p.Asp211fs)	Pathogenic
4795965	NM_001032382.2:c.641_642insC	Pathogenic
807471	NM_001032382.2(PQBP1):c.599_600del (p.Glu200fs)	Pathogenic
817349	NM_001032382.2(PQBP1):c.508del (p.Arg170fs)	Pathogenic
1030959	NM_001032382.2(PQBP1):c.32T>C (p.Leu11Ser)	Likely pathogenic
1802539	NM_001032382.2(PQBP1):c.233C>A (p.Pro78Gln)	Likely pathogenic
2443062	NM_001032382.2(PQBP1):c.721del (p.Gln241fs)	Likely pathogenic
3360559	NC_000023.11:g.48902777C>G	Likely pathogenic
422285	NM_001032382.2(PQBP1):c.738_742del (p.Ser247fs)	Likely pathogenic
422848	NM_001032382.2(PQBP1):c.637_640dup (p.Arg214fs)	Likely pathogenic
521007	NM_001032382.2(PQBP1):c.232C>T (p.Pro78Ser)	Likely pathogenic
637970	NM_001032382.2(PQBP1):c.722AGC[1] (p.Gln242del)	Likely pathogenic
816841	NM_001032382.2(PQBP1):c.463C>T (p.Arg155Ter)	Likely pathogenic
931434	NM_001032382.2(PQBP1):c.623C>A (p.Ser208Ter)	Likely pathogenic
977914	NM_001032382.2(PQBP1):c.727C>T (p.Arg243Trp)	Likely pathogenic

SpliceAI

2253 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48893726:T:TA	donor_gain	1.0000
X:48893896:TCA:T	donor_loss	1.0000
X:48893898:A:AC	donor_gain	1.0000
X:48893898:AC:A	donor_gain	1.0000
X:48893898:ACCAT:A	donor_loss	1.0000
X:48893899:C:CT	donor_gain	1.0000
X:48893899:CC:C	donor_gain	1.0000
X:48893899:CCA:C	donor_gain	1.0000
X:48893899:CCAT:C	donor_gain	1.0000
X:48893899:CCATT:C	donor_gain	1.0000
X:48894006:GCCAC:G	acceptor_gain	1.0000
X:48894007:CCAC:C	acceptor_gain	1.0000
X:48894007:CCACC:C	acceptor_gain	1.0000
X:48894008:CAC:C	acceptor_gain	1.0000
X:48894008:CACC:C	acceptor_gain	1.0000
X:48894009:AC:A	acceptor_gain	1.0000
X:48894010:CC:C	acceptor_gain	1.0000
X:48894011:C:CA	acceptor_loss	1.0000
X:48894011:C:CC	acceptor_gain	1.0000
X:48894012:T:A	acceptor_loss	1.0000
X:48894019:G:C	acceptor_gain	1.0000
X:48894019:G:GC	acceptor_gain	1.0000
X:48894020:T:C	acceptor_gain	1.0000
X:48894020:T:TC	acceptor_gain	1.0000
X:48894088:GTCAC:G	donor_loss	1.0000
X:48894089:TCACT:T	donor_loss	1.0000
X:48894090:CACT:C	donor_loss	1.0000
X:48894091:ACTCA:A	donor_loss	1.0000
X:48894093:TCA:T	donor_loss	1.0000
X:48894094:CA:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001415677 (X:48897616 C>G), RS1002020350 (X:48899569 C>G,T), RS1002454674 (X:48899973 G>A,T), RS1005526126 (X:48898738 C>T), RS1006576758 (X:48898296 A>G), RS1006942620 (X:48901156 A>C), RS1008591300 (X:48903364 T>G), RS1008707556 (X:48896374 T>C), RS1009646790 (X:48897645 C>T), RS1010686831 (X:48899993 G>T), RS1013813405 (X:48897524 C>T), RS1015118921 (X:48896572 G>A,C), RS1015151374 (X:48897172 C>T), RS1016595708 (X:48898774 G>A,T), RS1017573974 (X:48900653 C>T)

Disease associations

OMIM: gene MIM:300463 | disease phenotypes: MIM:309500

GenCC curated gene-disease

Disease	Classification	Inheritance
Renpenning syndrome	Definitive	X-linked
X-linked intellectual disability, Porteous type	Supportive	X-linked
hamel cerebro-palato-cardiac syndrome	Supportive	X-linked
X-linked intellectual disability, Golabi-Ito-hall type	Supportive	X-linked
X-linked intellectual disability, Sutherland-Haan type	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Renpenning syndrome	Definitive	XL

Mondo (8): Renpenning syndrome (MONDO:0010653), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), autism spectrum disorder (MONDO:0005258), X-linked intellectual disability, Porteous type (MONDO:0019766), hamel cerebro-palato-cardiac syndrome (MONDO:0019767), X-linked intellectual disability, Golabi-Ito-hall type (MONDO:0019768), X-linked intellectual disability, Sutherland-Haan type (MONDO:0019769)

Orphanet (3): Renpenning syndrome (Orphanet:3242), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000047	Hypospadias
HP:0000089	Renal hypoplasia
HP:0000158	Macroglossia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000378	Cupped ear
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537761	Renpenning syndrome 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
bleomycetin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Diazinon	increases methylation	1
Diethylstilbestrol	decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ketoconazole	decreases expression	1
Menthol	increases expression	1
Ribonucleotides	affects binding	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4XX	WMUi017-A	Induced pluripotent stem cell	Male
CVCL_B3EP	Abcam HEK293T PQBP1 KO	Transformed cell line	Female
CVCL_YC47	PEIi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

211 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders