KPNA7

protein-coding

karyopherin subunit alpha 7, the group of Importins|Armadillo repeat containing

Gene summary

The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import, but exhibits different nuclear localization signal binding specificity compared to other members of the family. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, Jul 2016]

MANE transcript

NM_001145715.3

Inheritance

ClinVar variants

P:3U:277B:169

Top phenotype

Oocyte/zygote/embryo maturation arrest 17

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr7:99,173,572-99,250,075

External References & Databases

Ensembl (ENSG00000185467)

Transcript & Mutation Effects

hg38 • Region Span ~76.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018430

Submitter: Orphanet

neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

oocyte/zygote/embryo maturation arrest 17STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957220

Submitter: Labcorp Genetics (formerly Invitae)

epilepsyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005027

Submitter: ClinGen

*KPNA7* was first reported in relation to autosomal recessive epilepsy in 2014 (Paciorkowski et al. PMID: 24045845). *KPNA7* has also been reported in association with oocyte/zygote/embryo maturation arrest (Wang et al. 2012 PMID: 22281085). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in phenotypic variability and have split out the disease entity oocyte/zygote/embryo maturation arrest (OMIM:620319), which will be assessed separately. At this time, only two probands have been reported in relation to epilepsy, with compound heterozygous missense variants in proband one (p.Pro339Ala and p.Glu344Gln) and a nonsense variant in proband two (p.Arg25Ter) (PMIDs: 24045845, 29302074). At this time, the mechanism of pathogenicity is unknown and no functional evidence is available for this gene-disease relationship. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Epilepsy GCEP on the meeting date 10/7/2025 (SOP version 11).

Clinical Genomic Database (CGD)

Oocyte/zygote/embryo maturation arrest 17AR

Manifestation: Obstetric

Intervention: General

Rationale: 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

Refs: 36647821

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KPNA7 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 503

not specifiedTotal: 101

KPNA7-related disorderTotal: 18

Oocyte/zygote/embryo maturation arrest 17Total: 7

Mild intellectual disabilityTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001145715.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	154 clinvar	1 clinvar	161
missense	1 clinvar		233 clinvar	11 clinvar	3 clinvar	248
nonsense		1 clinvar	14 clinvar			15
start loss			1 clinvar			1
frameshift	1 clinvar		17 clinvar			18
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	2	1	277	165	4	449

Highest pathogenic variant AF is 0.000021270725

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001145715.3	RefSeq	NP_001139187.1	10	MANE Select
ENST00000327442.7	Ensembl	ENSP00000330878.6	10	MANE Select
ENST00000681060.1	Ensembl	ENSP00000506489.1	10	Standard
ENST00000681060.2	Ensembl	ENSP00000506489.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Disease
NS1 Mediated Effects on Host Pathways
Host Interactions with Influenza Factors
Influenza Infection
Infectious disease

Biological Process

protein import into nucleus
modulation by virus of host process

Molecular Function

protein binding
protein transporter activity
nuclear import signal receptor activity

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327442
Coding exons: 10
Length: 33933
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.907	238	281	0.848	0.0000160	3327
Missense (PolyPhen)		75	96.747	0.77522		1223
Synonymous	1.13	104	120	0.869	0.00000756	1042
Loss of Function	0.236	23	24.3	0.948	0.00000147	254

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions in nuclear protein import. {ECO:0000250}.;

Intolerance Scores

RVIS EVS: 0.4
RVIS percentile EVS: 76.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.296

Gene Damage Prediction

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