NUP214

Chr 9AR

nucleoporin 214

Also known as: CAIN, CAN, IIAE9

NCBI Gene: 8021 ENSG00000126883 UniProt: P35658 OMIM: 114350

The protein is a nucleoporin that forms part of the nuclear pore complex and is essential for nucleocytoplasmic transport and proper cell cycle progression. Mutations cause autosomal recessive acute infection-induced encephalopathy with increased susceptibility during febrile episodes. The gene is highly constrained against loss-of-function variation (LOEUF 0.35), indicating that biallelic mutations likely have severe consequences for cellular function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene is a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is localized to the cytoplasmic face of the nuclear pore complex where it is required for proper cell cycle progression and nucleocytoplasmic transport. The 3' portion of this gene forms a fusion gene with the DEK gene on chromosome 6 in a t(6,9) translocation associated with acute myeloid leukemia and myelodysplastic syndrome. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.353 OMIM phenotypes

Clinical Summary— NUP214

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 344 VUS of 476 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.055

Z-score 6.53

OE 0.24 (0.17–0.35)

Highly constrained

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

Missense Constraint?

0.65Z-score

OE missense 0.95 (0.90–0.99)

1063 obs / 1124.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.17–0.35)

0≤0.351.4

Missense OE?0.95 (0.90–0.99)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 21 / 86.5Missense obs/exp: 1063 / 1124.7Syn Z: -0.31

ClinVar Variant Classifications

476 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic8

VUS344

Likely Benign53

Benign12

Conflicting1

Pathogenic

Likely Pathogenic

344

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	4	3	1	0	8
VUS	2	339	2	1	344
Likely Benign	0	26	3	24	53
Benign	0	5	0	7	12
Conflicting	—				1
Total	8	373	6	32	420

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap NUP214 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →