TNPO2

transportin 2, the group of Armadillo like helical domain containing|Importins|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 19:12699200-12724011

Links

ENSG00000105576 ∙ NCBI:30000 ∙ OMIM:603002 ∙ HGNC:19998 ∙ Uniprot:O14787 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal	34314705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNPO2 gene.

• not provided (20 variants)
• Inborn genetic diseases (13 variants)
• Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (9 variants)
• TNPO2-related condition (4 variants)
• not specified (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNPO2 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					4	4
missense		6	24	1	1	32
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			4		2	6
non coding						0
Total	0	7	27	1	5

Variants in TNPO2

This is a list of pathogenic ClinVar variants found in the TNPO2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-12701363-C-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
19-12701386-G-A		Inborn genetic diseases	Likely benign (Dec 17, 2023)
19-12701448-G-A			Benign (Feb 01, 2023)
19-12701609-T-G		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
19-12701679-C-T		not specified	Uncertain significance (Mar 13, 2024)
19-12701851-CC-AG			Uncertain significance (Jun 01, 2023)
19-12702141-G-A			Likely pathogenic (May 15, 2022)
19-12702168-G-A			Benign (Feb 20, 2018)
19-12702174-C-T		Inborn genetic diseases	Likely benign (Sep 26, 2022)
19-12703710-G-A		TNPO2-related disorder	Likely benign (Jun 15, 2022)
19-12703713-C-G		Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	Likely pathogenic (Jan 03, 2022)
19-12703730-A-G			Benign (Jul 04, 2018)
19-12703765-G-A		Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	Uncertain significance (Apr 20, 2022)
19-12703765-G-T		Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	Uncertain significance (Jan 01, 2023)
19-12703776-C-G		Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	Likely pathogenic (Oct 28, 2021)
19-12705277-C-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
19-12705288-C-G			Uncertain significance (Jan 01, 2024)
19-12705325-C-T			Uncertain significance (Mar 07, 2022)
19-12705332-G-GT		Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	Likely pathogenic (Mar 29, 2024)
19-12705349-A-C			Uncertain significance (Feb 13, 2020)
19-12705356-C-G			Uncertain significance (Sep 23, 2019)
19-12705494-T-G		Inborn genetic diseases	Uncertain significance (Aug 04, 2021)
19-12705561-G-T			Uncertain significance (Aug 14, 2019)
19-12705771-G-A		Inborn genetic diseases	Uncertain significance (Jul 22, 2022)
19-12706221-G-A		Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	Likely pathogenic (Feb 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNPO2	protein_coding	protein_coding	ENST00000425528	23	24818

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.13e-7	124634	0	5	124639	0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.88	152	534	0.284	0.0000319	5910
Missense in Polyphen		11	100.52	0.10943		1193
Synonymous	-0.146	235	232	1.01	0.0000159	1714
Loss of Function	6.20	2	48.6	0.0411	0.00000226	545

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)	0.0000358	0.0000354
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. 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). {ECO:0000250}.

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.55

Haploinsufficiency Scores

• pHI: 0.533
• hipred: Y
• hipred_score: 0.775
• ghis: 0.717

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.747

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnpo2

Gene ontology

• Biological process: NLS-bearing protein import into nucleus;ribosomal protein import into nucleus
• Cellular component: nucleus;cytoplasm;nuclear membrane;nuclear periphery
• Molecular function: protein binding;nuclear localization sequence binding;Ran GTPase binding;protein transporter activity