TNPO3

transportin 3, the group of Armadillo like helical domain containing|Importins

Basic information

Region (hg38): 7:128954179-129055173

Previous symbols: [ "LGMD1F" ]

Links

ENSG00000064419 ∙ NCBI:23534 ∙ OMIM:610032 ∙ HGNC:17103 ∙ Uniprot:Q9Y5L0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant limb-girdle muscular dystrophy type 1F (Strong), mode of inheritance: AD
• autosomal dominant limb-girdle muscular dystrophy type 1F (Supportive), mode of inheritance: AD
• autosomal dominant limb-girdle muscular dystrophy type 1F (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, limb-girdle, autosomal dominant 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	11222786; 23543484; 23667635

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNPO3 gene.

• Autosomal dominant limb-girdle muscular dystrophy type 1F (444 variants)
• not provided (171 variants)
• not specified (39 variants)
• Inborn genetic diseases (13 variants)
• TNPO3-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNPO3 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			12	100	7	119
missense		1	212	3		216
nonsense	1		6			7
start loss			2			2
frameshift		4	8			12
inframe indel						0
splice donor/acceptor (+/-2bp)		2	7			9
splice region			12	15	2	29
non coding			9	91	38	138
Total	1	7	256	194	45

Highest pathogenic variant AF is 0.0000197

Variants in TNPO3

This is a list of pathogenic ClinVar variants found in the TNPO3 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-128957252-GAGCTATCGAA-G		Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (May 25, 2022)
7-128957255-CT-C		Autosomal dominant limb-girdle muscular dystrophy type 1F	Pathogenic (May 07, 2013)
7-128957259-C-T		not specified • Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (Oct 04, 2022)
7-128957259-CG-C		Autosomal dominant limb-girdle muscular dystrophy type 1F	Likely pathogenic (Mar 09, 2022)
7-128957262-A-G		Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (Mar 12, 2022)
7-128957266-AC-A			Likely pathogenic (Oct 01, 2021)
7-128957271-G-A		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
7-128957272-TG-T		Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (Dec 12, 2022)
7-128957276-G-T		Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (Dec 07, 2023)
7-128957286-G-A		Autosomal dominant limb-girdle muscular dystrophy type 1F • TNPO3-related disorder	Conflicting classifications of pathogenicity (Apr 01, 2024)
7-128957309-C-T		Autosomal dominant limb-girdle muscular dystrophy type 1F	Conflicting classifications of pathogenicity (Jan 04, 2023)
7-128957533-T-G			Benign (Jun 14, 2018)
7-128957582-T-C			Likely benign (Nov 10, 2018)
7-128966993-C-T			Likely benign (Aug 03, 2018)
7-128967262-AC-A		Autosomal dominant limb-girdle muscular dystrophy type 1F	Benign (Aug 10, 2023)
7-128967263-C-G		Autosomal dominant limb-girdle muscular dystrophy type 1F	Likely benign (Feb 25, 2023)
7-128967264-C-A		Autosomal dominant limb-girdle muscular dystrophy type 1F	Likely benign (Apr 21, 2023)
7-128967269-G-T		Autosomal dominant limb-girdle muscular dystrophy type 1F	Likely benign (Sep 30, 2022)
7-128967283-G-C			Uncertain significance (Feb 12, 2018)
7-128967285-G-C		Autosomal dominant limb-girdle muscular dystrophy type 1F	Likely benign (Nov 18, 2023)
7-128967314-T-G		Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (Oct 07, 2021)
7-128967315-G-C			Uncertain significance (Feb 02, 2017)
7-128967317-G-A		Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (Aug 03, 2021)
7-128967317-G-T		Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (Jul 12, 2022)
7-128967318-T-C		Autosomal dominant limb-girdle muscular dystrophy type 1F	Likely benign (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNPO3	protein_coding	protein_coding	ENST00000265388	22	100251

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000175	1.00	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.44	300	521	0.576	0.0000286	6015
Missense in Polyphen		58	131.76	0.44021		1481
Synonymous	0.983	173	190	0.909	0.00000979	1826
Loss of Function	4.56	21	58.7	0.358	0.00000355	610

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000218	0.000217
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000187	0.000185
Middle Eastern	0.000218	0.000217
South Asian	0.000197	0.000196
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins RBM4, SFRS1 and SFRS2, by recognizing phosphorylated RS domains. {ECO:0000269|PubMed:10366588, ECO:0000269|PubMed:10713112, ECO:0000269|PubMed:11517331, ECO:0000269|PubMed:12628928}.

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.301
• rvis_EVS: -1.18
• rvis_percentile_EVS: 5.94

Haploinsufficiency Scores

• pHI: 0.608
• hipred: Y
• hipred_score: 0.526
• ghis: 0.664

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.867

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnpo3
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: tnpo3
• Affected structure: thymus
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein import into nucleus
• Cellular component: nucleus;cytoplasm;intracellular membrane-bounded organelle
• Molecular function: protein binding;protein transporter activity;signaling receptor activity;identical protein binding