KPNA4

Chr 3

karyopherin subunit alpha 4

Also known as: IPOA3, QIP1, SRP3

NCBI Gene: 3840 ENSG00000186432 UniProt: O00629

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.16

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.16LOEUF

pLI 1.000

Z-score 4.94

OE 0.03 (0.01–0.16)

Highly constrained

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

Missense Constraint?

3.23Z-score

OE missense 0.43 (0.36–0.50)

107 obs / 251.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.16)

0≤0.351.4

Missense OE?0.43 (0.36–0.50)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 1 / 30.4Missense obs/exp: 107 / 251.0Syn Z: 0.29

Background carrier burden — how many people carry a rare variant somewhere in KPNA4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

393 rare PASS variants

Rare truncating (LoF)

1 in 3,300

32 rare PASS variants

Rare synonymous (reference)

1 in 150

221 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KPNA4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 340	1 in 11,000
South Asian	~43k	1 in 230	1 in 1,400
Remaining (unassigned)	~30k	1 in 200	≈ 1 in 30,000
European (Finnish)	~27k	1 in 610	1 in 1,700
Admixed American	~22k	1 in 280	≈ 1 in 16,000
African / African American	~21k	1 in 200	1 in 3,700
East Asian	~20k	1 in 200	1 in 2,300
Ashkenazi Jewish	~13k	1 in 820	none seen
Middle Eastern	~2,883	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 17 coding exons well covered in gnomAD exomes; exons 2, 3, 5, 6, 10 and 3 more marginal. Genomes: 16 of 17 (exon 3 below).? see exons ↓