KPNA4

Chr 3

karyopherin subunit alpha 4

Also known as: IPOA3, QIP1, SRP3

The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex. The protein encoded by this gene shares the sequence similarity with Xenopus importin-alpha and Saccharomyces cerevisiae Srp1. This protein is found to interact with the NLSs of DNA helicase Q1 and SV40 T antigen. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
LOEUF 0.16
Clinical SummaryKPNA4
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 VUS of 45 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.16LOEUF
pLI 1.000
Z-score 4.94
OE 0.03 (0.010.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.23Z-score
OE missense 0.43 (0.360.50)
107 obs / 251.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.03 (0.010.16)
00.351.4
Missense OE?0.43 (0.360.50)
00.61.4
Synonymous OE?0.96
01.21.6
LoF obs/exp: 1 / 30.4Missense obs/exp: 107 / 251.0Syn Z: 0.29

ClinVar Variant Classifications

45 submitted variants in ClinVar

Classification Summary

VUS18
Likely Benign1
Benign1
18
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
18
0
0
18
Likely Benign
0
0
1
0
1
Benign
0
0
1
0
1
Total0182020

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap KPNA4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

KPNA4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →