PTBP1

protein-coding

polypyrimidine tract binding protein 1, the group of MicroRNA protein coding host genes|RNA binding motif containing|Heterogeneous nuclear ribonucleoproteins

Gene summary

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA-binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has four repeats of quasi-RNA recognition motif (RRM) domains that bind RNAs. This protein binds to the intronic polypyrimidine tracts that requires pre-mRNA splicing and acts via the protein degradation ubiquitin-proteasome pathway. It may also promote the binding of U2 snRNP to pre-mRNAs. This protein is localized in the nucleoplasm and it is also detected in the perinucleolar structure. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_002819.5

Inheritance

—

ClinVar variants

P:10U:77B:20

Top phenotype

PTBP1-related neurodevelopmental disorder with skeletal dysplasia

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr19:797,075-812,327

External References & Databases

Ensembl (ENSG00000011304)

Transcript & Mutation Effects

hg38 • Region Span ~15.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTBP1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 28

PTBP1-related neurodevelopmental disorder with skeletal dysplasiaTotal: 10

STAD syndromeTotal: 9

PTBP1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002819.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	11 clinvar	6 clinvar	19
missense	3 clinvar		65 clinvar	3 clinvar		71
nonsense						0
start loss	5 clinvar	2 clinvar				7
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	8	2	77	14	6	107

Highest pathogenic variant AF is 7.0483685e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002819.5	RefSeq	NP_002810.1	15	MANE Select
ENST00000356948.11	Ensembl	ENSP00000349428.4	15	MANE Select
NM_001411140.1	RefSeq	NP_001398069.1	15	Standard
NM_031990.4	RefSeq	NP_114367.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ptbp1a	Danio rerio	Structure: mid intestine epithelium Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

ptbp1a

Danio rerio

Structure: mid intestine epithelium

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
mir-124 predicted interactions with cell cycle and differentiation
mRNA Processing
FGFR2 alternative splicing

Biological Process

regulation of alternative mRNA splicing, via spliceosome
mRNA splicing, via spliceosome
mRNA processing
RNA splicing
fibroblast growth factor receptor signaling pathway

Molecular Function

RNA binding
protein binding
poly-pyrimidine tract binding
pre-mRNA binding

Cellular Component

nucleoplasm
nucleolus
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356948
Coding exons: 15
Length: 15253
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125736
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.65	276	365	0.757	0.0000246	3627
Missense (PolyPhen)		19	68.021	0.27933		867
Synonymous	-4.97	247	166	1.49	0.0000130	1105
Loss of Function	4.63	1	26.9	0.0371	0.00000134	299

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10 (PubMed:15009664). In case of infection by picornaviruses, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:21518806). {ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:16179478, ECO:0000269|PubMed:16260624, ECO:0000269|PubMed:21518792, ECO:0000269|PubMed:21518806}.;

Recessive Scores

pRec: 0.248

Intolerance Scores

LoFtool: 0.184
RVIS EVS: -1.22
RVIS percentile EVS: 5.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

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