KPNA3

karyopherin subunit alpha 3, the group of Armadillo repeat containing|Importins

Basic information

Region (hg38): 13:49699320-49792682

Links

ENSG00000102753 ∙ NCBI:3839 ∙ OMIM:601892 ∙ HGNC:6396 ∙ Uniprot:O00505 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spastic paraplegia 88, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 88, autosomal dominant	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	Neurologic	34564892; 34825409; 34981581

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KPNA3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KPNA3 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				1		1
missense		2	13	1	1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	13	2	1

Variants in KPNA3

This is a list of pathogenic ClinVar variants found in the KPNA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-49702390-T-G		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
13-49702435-A-G		Spastic paraplegia 88, autosomal dominant	Uncertain significance (Sep 22, 2024)
13-49702470-T-G		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
13-49705729-C-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
13-49705773-A-C		Spastic paraplegia 88, autosomal dominant	Pathogenic (Nov 02, 2022)
13-49706276-G-C		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
13-49706289-C-T		Spastic paraplegia 88, autosomal dominant	Uncertain significance (Feb 14, 2024)
13-49706324-C-T			Uncertain significance (Dec 30, 2022)
13-49706356-A-G		Spastic paraplegia 88, autosomal dominant	Pathogenic (Nov 02, 2022)
13-49709576-T-G		not specified	Uncertain significance (Aug 14, 2023)
13-49709598-A-T		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
13-49709603-A-C		Spastic paraplegia 88, autosomal dominant	Pathogenic (Nov 02, 2022)
13-49709621-A-G		Spastic paraplegia 88, autosomal dominant	Pathogenic (Nov 02, 2022)
13-49709659-G-A			Likely benign (Mar 01, 2024)
13-49709660-G-A		Spastic paraplegia 88, autosomal dominant	Likely pathogenic (Mar 01, 2024)
13-49709678-C-T		Inborn genetic diseases	Uncertain significance (May 28, 2024)
13-49721985-A-T		Inborn genetic diseases	Uncertain significance (Mar 11, 2024)
13-49722025-T-C			Likely pathogenic (Nov 01, 2022)
13-49722055-C-T		Inborn genetic diseases	Likely benign (Mar 30, 2024)
13-49722076-T-C		Inborn genetic diseases	Uncertain significance (May 21, 2024)
13-49722533-C-T		Inborn genetic diseases	Likely benign (Sep 29, 2022)
13-49725420-C-A		Spastic paraplegia 88, autosomal dominant	Uncertain significance (Apr 04, 2024)
13-49725481-G-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
13-49732392-T-C			Benign (Jan 01, 2023)
13-49732764-G-C			Uncertain significance (Feb 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KPNA3	protein_coding	protein_coding	ENST00000261667	17	93611

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.954	0.0464	125729	0	9	125738	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.39	110	266	0.414	0.0000125	3421
Missense in Polyphen		25	116.03	0.21547		1511
Synonymous	-0.585	98	90.9	1.08	0.00000444	973
Loss of Function	4.39	5	31.7	0.158	0.00000152	391

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000210	0.000198
East Asian	0.00	0.00
Finnish	0.0000931	0.0000924
European (Non-Finnish)	0.0000455	0.0000440
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 an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats 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 importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. 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. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non- classical NLS. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9.
• Pathway: miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Disease;NS1 Mediated Effects on Host Pathways;Host Interactions with Influenza Factors;Influenza Infection;Infectious disease;TNFalpha (Consensus)

Recessive Scores

• pRec: 0.224

Intolerance Scores

• loftool: 0.476
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.708
• hipred: Y
• hipred_score: 0.748
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kpna3
• Phenotype: normal phenotype

Gene ontology

• Biological process: NLS-bearing protein import into nucleus;modulation by virus of host process;viral entry into host cell;protein-containing complex assembly;viral penetration into host nucleus
• Cellular component: nuclear pore;nucleoplasm;cytosol;host cell
• Molecular function: protein binding;protein C-terminus binding;nuclear localization sequence binding;protein transporter activity;nuclear import signal receptor activity