TNPO1

transportin 1, the group of Importins|Armadillo like helical domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 5:72816312-72916733

Previous symbols: [ "KPNB2" ]

Links

ENSG00000083312 ∙ NCBI:3842 ∙ OMIM:602901 ∙ HGNC:6401 ∙ Uniprot:Q92973 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNPO1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNPO1 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				6	1	7
missense			22		1	23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding				3		3
Total	0	0	22	9	2

Variants in TNPO1

This is a list of pathogenic ClinVar variants found in the TNPO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-72816731-G-A		TNPO1-related disorder	Likely benign (May 28, 2019)
5-72848388-A-T		not specified	Uncertain significance (Aug 20, 2023)
5-72855848-G-A		not specified	Uncertain significance (May 29, 2024)
5-72855931-A-G		TNPO1-related disorder	Benign (Jul 31, 2019)
5-72861810-A-G		not specified	Uncertain significance (Mar 07, 2024)
5-72861812-T-C		TNPO1-related disorder	Likely benign (Jul 11, 2019)
5-72861900-T-A		not specified	Uncertain significance (Nov 29, 2023)
5-72861900-T-C		not specified	Uncertain significance (Sep 13, 2023)
5-72865610-C-T		TNPO1-related disorder	Likely benign (May 28, 2019)
5-72865641-A-G		not specified	Uncertain significance (Jun 16, 2024)
5-72865665-C-T		TNPO1-related disorder	Uncertain significance (Feb 03, 2023)
5-72877257-T-G		not specified	Uncertain significance (Dec 16, 2022)
5-72877271-T-C		not specified	Uncertain significance (Nov 07, 2023)
5-72877324-G-A		not specified	Uncertain significance (Jan 03, 2024)
5-72877342-C-T		TNPO1-related disorder	Benign (Nov 25, 2019)
5-72883099-T-C		TNPO1-related disorder	Likely benign (Oct 17, 2019)
5-72883119-G-A		not specified	Uncertain significance (Jan 20, 2023)
5-72883177-A-C		not specified	Uncertain significance (Mar 01, 2023)
5-72887090-C-G		not specified	Uncertain significance (Feb 22, 2023)
5-72887168-C-T		not specified	Uncertain significance (Jun 07, 2024)
5-72887228-CCTAAGTCCAGTTTGAATTATGTAAGTTGGCTTCTTACTACTATTAGGTACTAATAAGGCTAGGCTACTTTAAGG-C			Benign (Dec 31, 2019)
5-72888068-T-G		TNPO1-related disorder	Likely benign (Mar 28, 2023)
5-72888132-A-G		not specified	Uncertain significance (Jul 26, 2023)
5-72888143-G-A		not specified	Uncertain significance (Jun 10, 2024)
5-72888152-G-T		not specified	Uncertain significance (Dec 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNPO1	protein_coding	protein_coding	ENST00000337273	24	100422

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.74e-9	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.33	216	484	0.447	0.0000247	5978
Missense in Polyphen		16	90.727	0.17635		1162
Synonymous	0.333	162	167	0.967	0.00000864	1635
Loss of Function	6.77	0	53.4	0.00	0.00000267	631

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: Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates (PubMed:24753571). Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Involved in nuclear import of M9- containing proteins. In vitro, binds directly to the M9 region of the heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2 and mediates their nuclear import. Appears also to be involved in hnRNP A1/A2 nuclear export. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones, and SRP19 (By similarity). Mediates nuclear import of ADAR/ADAR1 isoform 1 and isoform 5 in a RanGTP-dependent manner (PubMed:19124606, PubMed:24753571). {ECO:0000250|UniProtKB:Q8BFY9, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:19124606, ECO:0000269|PubMed:24753571, ECO:0000269|PubMed:8986607, ECO:0000269|PubMed:9687515}.
• Pathway: Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA;Metabolism of RNA;Regulation of mRNA stability by proteins that bind AU-rich elements;Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.183

Intolerance Scores

• loftool: 0.0473
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.77

Haploinsufficiency Scores

• pHI: 0.971
• hipred: Y
• hipred_score: 0.825
• ghis: 0.694

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnpo1

Zebrafish Information Network

• Gene name: tnpo1
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: obsolete protein import into nucleus, translocation;NLS-bearing protein import into nucleus;ribosomal protein import into nucleus;viral process;intraciliary transport involved in cilium assembly;regulation of mRNA stability
• Cellular component: nucleus;cytoplasm;cytosol;cilium;nuclear membrane;nuclear periphery;extracellular exosome
• Molecular function: RNA binding;protein binding;nuclear localization sequence binding;Ran GTPase binding;protein transporter activity