GeneBe

TNPO1

protein-coding

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

Gene summary

This gene encodes the beta subunit of the karyopherin receptor complex which interacts with nuclear localization signals to target nuclear proteins to the nucleus. The karyopherin receptor complex is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. Alternate splicing of this gene results in several transcript variants encoding different proteins. [provided by RefSeq, Jun 2018]

Previous symbols:
  • KPNB2

MANE transcript

NM_002270.4

Inheritance

—

ClinVar variants

U:73B:9

Top phenotype

TNPO1-related disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr5:72,816,312-72,916,733

External References & Databases

Ensembl (ENSG00000083312)NCBI Gene (3842)OMIM (602901)HGNC:6401GenCCUniProt (Q92973)AlphaFoldClinVar (TNPO1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~100.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TNPO1 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 56
TNPO1-related disorderTotal: 13
not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002270.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
7
clinvar
1
clinvar
 10
missense
64
clinvar
1
clinvar
 65
nonsense
1
clinvar
 1
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total00737282
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002270.4RefSeqNP_002261.324MANE Select
ENST00000337273.10EnsemblENSP00000336712.524MANE Select
NM_001364292.3RefSeqNP_001351221.123Standard
NM_001364293.3RefSeqNP_001351222.123Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
tnpo1Danio rerio

Structure: slow muscle cell

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

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

Molecular Function

  • RNA binding
  • protein binding
  • nuclear localization sequence binding
  • Ran GTPase binding
  • protein transporter activity

Cellular Component

  • nucleus
  • cytoplasm
  • cytosol
  • cilium
  • nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000337273
Coding exons
24
Length
100422
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense4.332164840.4470.00002475978
Missense (PolyPhen)1690.7270.176351162
Synonymous0.3331621670.9670.000008641635
Loss of Function6.77053.40.000.00000267631

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.183

Intolerance Scores

LoFtool
0.0473
RVIS EVS
-0.78
RVIS percentile EVS
12.77

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.928

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.