IPO8

importin 8, the group of Importins

Basic information

Region (hg38): 12:30628988-30695869

Previous symbols: [ "RANBP8" ]

Links

ENSG00000133704 ∙ NCBI:10526 ∙ OMIM:605600 ∙ HGNC:9853 ∙ Uniprot:O15397 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• VISS syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
VISS syndrome	AR	Cardiovascular	Among ohther findings, the condition can include increased risk of aneurysms and other cardiovascular anomalies, and awareness may enable surveillance and early interventions	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Pulmonary	34010604; 34010605

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IPO8 gene.

• IPO8-related aortopathy (7 variants)
• VISS syndrome (6 variants)
• IPO8 related Connective tissue disorder (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IPO8 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				10		10
missense		3	42	1	1	47
nonsense	3	4				7
start loss						0
frameshift	5	1				6
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region	1		1	5	1	8
non coding					1	1
Total	9	10	42	11	2

Highest pathogenic variant AF is 0.0000131

Variants in IPO8

This is a list of pathogenic ClinVar variants found in the IPO8 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-30630885-A-T		Inborn genetic diseases	Uncertain significance (Jun 27, 2022)
12-30630927-C-A			Conflicting classifications of pathogenicity (Apr 18, 2023)
12-30630952-T-C		Inborn genetic diseases	Uncertain significance (Feb 01, 2023)
12-30630954-G-C		Inborn genetic diseases • IPO8-related disorder	Uncertain significance (May 25, 2022)
12-30631907-G-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
12-30631907-G-T			Likely benign (Mar 01, 2023)
12-30631959-G-A			Likely benign (Mar 01, 2023)
12-30631984-T-A		Inborn genetic diseases	Uncertain significance (Dec 06, 2022)
12-30631990-G-T		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
12-30632009-C-T		Inborn genetic diseases	Uncertain significance (Jun 16, 2023)
12-30632012-C-T		VISS syndrome • IPO8 related Connective tissue disorder • IPO8-related aortopathy	Pathogenic/Likely pathogenic (Jun 29, 2022)
12-30634125-T-C		Inborn genetic diseases	Uncertain significance (Jun 21, 2023)
12-30634159-C-T		IPO8-related disorder	Likely benign (Jun 29, 2023)
12-30634160-G-A		Inborn genetic diseases	Uncertain significance (Aug 10, 2021)
12-30634208-T-G		Inborn genetic diseases	Uncertain significance (Apr 06, 2023)
12-30634255-A-G			Likely benign (Mar 01, 2023)
12-30636973-AGACTT-A		VISS syndrome	Pathogenic (Aug 12, 2021)
12-30636974-GACTTT-G		IPO8 related Connective tissue disorder	Pathogenic (Apr 22, 2021)
12-30637024-C-T			Uncertain significance (Jan 23, 2024)
12-30637026-C-T		Inborn genetic diseases	Uncertain significance (Dec 18, 2023)
12-30637027-G-C		Inborn genetic diseases	Uncertain significance (Nov 19, 2022)
12-30637041-C-T			Benign (Aug 01, 2024)
12-30637045-T-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
12-30637047-G-T		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
12-30637075-GGAAAA-G		VISS syndrome • IPO8-related aortopathy	Pathogenic (Mar 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IPO8	protein_coding	protein_coding	ENST00000256079	25	66999

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.234	0.766	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.12	408	547	0.745	0.0000274	6855
Missense in Polyphen		50	110.02	0.45446		1374
Synonymous	-0.316	195	189	1.03	0.00000940	1884
Loss of Function	5.71	15	64.5	0.232	0.00000354	729

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000340	0.000334
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to function in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter- like protein in association with the importin-beta subunit KPNB1. Acting autonomously, is thought to serve itself as receptor for nuclear localization signals (NLS) and to promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to 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. In vitro mediates the nuclear import of SRP19. {ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9214382}.
• Pathway: Gene expression (Transcription);Transcriptional regulation by small RNAs;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.677
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.07

Haploinsufficiency Scores

• pHI: 0.264
• hipred: Y
• hipred_score: 0.601
• ghis: 0.670

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.808

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ipo8

Gene ontology

• Biological process: protein import into nucleus;signal transduction;regulation of gene silencing by miRNA
• Cellular component: nuclear envelope;nucleoplasm;cytosol
• Molecular function: protein binding;Ran GTPase binding;protein transporter activity