PQBP1

polyglutamine binding protein 1, the group of Spliceosomal B complex

Basic information

Region (hg38): X:48890196-48903402

Previous symbols: [ "RENS1", "MRXS8", "SHS", "MRX55", "MRX2", "MRXS3" ]

Links

ENSG00000102103 ∙ NCBI:10084 ∙ OMIM:300463 ∙ HGNC:9330 ∙ Uniprot:O60828 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Renpenning syndrome (Definitive), mode of inheritance: XLR
• Renpenning syndrome (Strong), mode of inheritance: XL
• X-linked intellectual disability, Porteous type (Supportive), mode of inheritance: XL
• hamel cerebro-palato-cardiac syndrome (Supportive), mode of inheritance: XL
• X-linked intellectual disability, Golabi-Ito-hall type (Supportive), mode of inheritance: XL
• X-linked intellectual disability, Sutherland-Haan type (Supportive), mode of inheritance: XL
• Renpenning syndrome (Definitive), mode of inheritance: XL
• Renpenning syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renpenning syndrome 1	XL	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	13981686; 3177467; 7943045; 9599645; 11950858; 14634649; 15024694; 15811016; 15782410; 16493439; 16740914; 17033686; 20886605; 20950397; 21204222; 21267006; 21315190; 22710169

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PQBP1 gene.

• not provided (101 variants)
• Renpenning syndrome (41 variants)
• Inborn genetic diseases (32 variants)
• not specified (13 variants)
• PQBP1-related condition (3 variants)
• See cases (3 variants)
• Intellectual disability (2 variants)
• History of neurodevelopmental disorder (2 variants)
• Microcephaly;Delayed speech and language development;Hyperactivity (1 variants)
• Intellectual disability, mild (1 variants)
• Microcephaly (1 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PQBP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	14	4	19
missense	1	5	53	3		62
nonsense	2	3				5
start loss						0
frameshift	7	5	1			13
inframe indel	1	1	4	1		7
splice donor/acceptor (+/-2bp)	1	1				2
splice region			2	4	2	8
non coding			11	10	5	26
Total	12	15	70	28	9

Variants in PQBP1

This is a list of pathogenic ClinVar variants found in the PQBP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-48893757-C-T		not specified	Uncertain significance (Nov 08, 2022)
X-48893769-G-T			Likely benign (Mar 01, 2023)
X-48893902-T-C		not specified	Uncertain significance (Dec 02, 2021)
X-48893927-G-A		not specified	Uncertain significance (Dec 05, 2022)
X-48893945-C-T		not specified	Uncertain significance (Jul 09, 2021)
X-48894124-A-G			Likely benign (Aug 01, 2022)
X-48894165-C-T		not specified	Uncertain significance (Dec 18, 2023)
X-48894169-G-A		not specified	Uncertain significance (May 18, 2022)
X-48894171-C-T		not specified	Uncertain significance (Oct 26, 2022)
X-48895094-C-T		not specified	Uncertain significance (Jan 10, 2022)
X-48897735-A-G			Likely benign (Dec 01, 2022)
X-48897739-T-A		not specified	Uncertain significance (Apr 12, 2022)
X-48897951-A-G			Likely benign (Oct 05, 2019)
X-48898097-G-A			Benign (Jul 07, 2018)
X-48898207-G-T			Likely benign (Jun 16, 2018)
X-48898296-A-G		Renpenning syndrome	Uncertain significance (Jan 13, 2018)
X-48898423-C-T		Renpenning syndrome	Benign (Jan 13, 2018)
X-48898533-G-T			Uncertain significance (Aug 31, 2022)
X-48898536-C-A			Likely benign (Dec 02, 2021)
X-48898537-C-T			Uncertain significance (Jun 29, 2023)
X-48898538-G-T			Uncertain significance (Oct 13, 2020)
X-48898541-T-C		Renpenning syndrome	Likely pathogenic (May 12, 2020)
X-48898562-A-G			Uncertain significance (Dec 12, 2023)
X-48898568-T-A			Uncertain significance (Dec 04, 2022)
X-48898569-G-C			Benign (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PQBP1	protein_coding	protein_coding	ENST00000218224	6	5226

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.789	0.209	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.92	65	126	0.518	0.0000111	1712
Missense in Polyphen		16	50.663	0.31581		664
Synonymous	0.232	48	50.1	0.958	0.00000441	515
Loss of Function	2.56	1	9.51	0.105	7.31e-7	159

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:10198427, PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species (PubMed:10332029, PubMed:12062018, PubMed:23512658, PubMed:20410308). 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 (PubMed:10198427). May be involved in ATXN1 mutant-induced cell death (PubMed:12062018). The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit (PubMed:12062018). Involved in the assembly of cytoplasmic stress granule, possibly by participating to the transport of neuronal RNA granules (PubMed:21933836). 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 (PubMed:26046437). 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 (PubMed:26046437). {ECO:0000269|PubMed:10198427, ECO:0000269|PubMed:10332029, ECO:0000269|PubMed:12062018, ECO:0000269|PubMed:20410308, ECO:0000269|PubMed:21933836, ECO:0000269|PubMed:23512658, ECO:0000269|PubMed:26046437}.
• Disease: DISEASE: Renpenning syndrome 1 (RENS1) [MIM:309500]: A X-linked mental retardation syndrome characterized by mental retardation, 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. {ECO:0000269|PubMed:14634649, ECO:0000269|PubMed:16740914, ECO:0000269|PubMed:20410308, ECO:0000269|PubMed:21315190, ECO:0000269|PubMed:23512658, ECO:0000269|PubMed:26046437}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Spliceosome - Homo sapiens (human);Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.226
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.124
• hipred: Y
• hipred_score: 0.744
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.914

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pqbp1

Gene ontology

• Biological process: alternative mRNA splicing, via spliceosome;mRNA splicing, via spliceosome;activation of innate immune response;positive regulation of defense response to virus by host;regulation of transcription, DNA-templated;neuron projection development;positive regulation of type I interferon production;regulation of RNA splicing;innate immune response;regulation of dendrite morphogenesis;defense response to virus;cellular response to exogenous dsRNA;positive regulation of nucleic acid-templated transcription
• Cellular component: nucleus;nucleoplasm;cytosol;cytoplasmic stress granule;nuclear speck;neuronal ribonucleoprotein granule
• Molecular function: DNA binding;double-stranded DNA binding;transcription coactivator activity;protein binding;ribonucleoprotein complex binding