NUP214

nucleoporin 214, the group of Nucleoporins

Basic information

Region (hg38): 9:131125573-131234663

Links

ENSG00000126883 ∙ NCBI:8021 ∙ OMIM:114350 ∙ HGNC:8064 ∙ Uniprot:P35658 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• encephalopathy, acute, infection-induced, susceptibility to, 9 (Limited), mode of inheritance: AR
• encephalopathy, acute, infection-induced, susceptibility to, 9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, acute, infection-induced, suseptibility to, 9	AR	General	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	Neurologic	30758658; 31178128

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NUP214 gene.

• NUP14 Related Disorders (2 variants)
• Encephalopathy, acute, infection-induced, susceptibility to, 9 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUP214 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				15	7	22
missense		2	197	15	5	219
nonsense		1				1
start loss						0
frameshift	3	1	2			6
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			1			1
Total	3	4	202	30	12

Variants in NUP214

This is a list of pathogenic ClinVar variants found in the NUP214 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-131127519-A-G			Likely benign (Apr 19, 2018)
9-131127539-G-C		not specified	Uncertain significance (Aug 04, 2024)
9-131127540-C-T		not specified	Uncertain significance (Feb 28, 2024)
9-131127541-G-A			Likely benign (Mar 30, 2018)
9-131127569-C-G		not specified	Uncertain significance (Mar 07, 2025)
9-131127590-C-T		Progressive microcephaly;Recurrent encephalopathy • Encephalopathy, acute, infection-induced, susceptibility to, 9	Pathogenic/Likely pathogenic (Dec 11, 2022)
9-131127594-C-T		Encephalopathy, acute, infection-induced, susceptibility to, 9	Uncertain significance (Jun 03, 2020)
9-131127611-T-A		not specified	Uncertain significance (Aug 16, 2021)
9-131127618-A-G		not specified	Uncertain significance (Oct 06, 2023)
9-131127620-T-C		not specified	Uncertain significance (May 20, 2024)
9-131127647-A-C			Uncertain significance (Mar 24, 2023)
9-131127675-ATCT-A		Acute myeloid leukemia	Uncertain significance (-)
9-131127683-A-C		not specified	Uncertain significance (Feb 17, 2022)
9-131127697-C-T			Likely benign (Jun 15, 2018)
9-131128358-C-G			Uncertain significance (Feb 01, 2024)
9-131128361-A-G		not specified	Uncertain significance (Jun 24, 2022)
9-131128376-C-T			Uncertain significance (Mar 07, 2022)
9-131128392-G-C		not specified	Uncertain significance (Feb 14, 2023)
9-131128409-C-T			Uncertain significance (Oct 22, 2019)
9-131128416-C-T			Benign (Dec 31, 2019)
9-131128421-A-G		not specified	Uncertain significance (Jun 29, 2023)
9-131128431-G-T		not specified	Uncertain significance (Nov 22, 2023)
9-131129297-C-G		not specified	Uncertain significance (Mar 10, 2025)
9-131129302-T-G		Encephalopathy, acute, infection-induced, susceptibility to, 9	Uncertain significance (Dec 11, 2022)
9-131129343-T-C		not specified	Uncertain significance (Oct 21, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NUP214	protein_coding	protein_coding	ENST00000359428	36	109110

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0547	0.945	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.653	1063	1.12e+3	0.945	0.0000593	13334
Missense in Polyphen		139	173.87	0.79946		1905
Synonymous	-0.308	459	451	1.02	0.0000271	4584
Loss of Function	6.53	21	86.5	0.243	0.00000445	1042

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000592	0.000577
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000221	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000221	0.000217
South Asian	0.000298	0.000294
Other	0.000494	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex. {ECO:0000303|PubMed:8108440}.
• Disease: DISEASE: Note=A chromosomal aberration involving NUP214 is found in a subset of acute myeloid leukemia (AML); also known as acute non-lymphocytic leukemia. Translocation t(6;9)(p23;q34) with DEK. It results in the formation of a DEK-CAN fusion gene. {ECO:0000269|PubMed:1549122}.; DISEASE: Note=A chromosomal aberration involving NUP214 is found in some cases of acute undifferentiated leukemia (AUL). Translocation t(6;9)(q21;q34.1) with SET. {ECO:0000269|PubMed:1630450}.
• Pathway: RNA transport - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);TGF-Ncore;TGF-beta Signaling Pathway;tRNA processing;Disease;Gene expression (Transcription);sumoylation by ranbp2 regulates transcriptional repression;cycling of ran in nucleocytoplasmic transport;Regulation of HSF1-mediated heat shock response;Metabolism of carbohydrates;Rev-mediated nuclear export of HIV RNA;Late Phase of HIV Life Cycle;HIV Life Cycle;Interactions of Rev with host cellular proteins;Host Interactions of HIV factors;HIV Infection;snRNP Assembly;Vpr-mediated nuclear import of PICs;SUMOylation of DNA damage response and repair proteins;Transport of Ribonucleoproteins into the Host Nucleus;Viral Messenger RNA Synthesis;Export of Viral Ribonucleoproteins from Nucleus;SUMOylation of chromatin organization proteins;Influenza Viral RNA Transcription and Replication;Cellular responses to stress;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;NEP/NS2 Interacts with the Cellular Export Machinery;Metabolism of proteins;Influenza Life Cycle;Influenza Infection;Metabolism of RNA;Glycolysis and Gluconeogenesis;Infectious disease;Leukotriene metabolism;Squalene and cholesterol biosynthesis;Purine metabolism;Vitamin B3 (nicotinate and nicotinamide) metabolism;Vitamin B5 - CoA biosynthesis from pantothenate;Metabolism;Transport of the SLBP independent Mature mRNA;Transport of the SLBP Dependant Mature mRNA;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Mature mRNAs Derived from Intronless Transcripts;Pyrimidine metabolism;SUMOylation;Glycosphingolipid metabolism;Cellular responses to external stimuli;Regulation of Glucokinase by Glucokinase Regulatory Protein;Glycolysis;Phosphatidylinositol phosphate metabolism;Lysine metabolism;Methionine and cysteine metabolism;Selenoamino acid metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Aminosugars metabolism;Pentose phosphate pathway;Nuclear Pore Complex (NPC) Disassembly;De novo fatty acid biosynthesis;Glycerophospholipid metabolism;Prostaglandin formation from dihomo gama-linoleic acid;Putative anti-Inflammatory metabolites formation from EPA;Vitamin D3 (cholecalciferol) metabolism;Vitamin E metabolism;tRNA processing in the nucleus;TGF_beta_Receptor;Transport of Mature mRNA derived from an Intron-Containing Transcript;mechanism of protein import into the nucleus;BMP receptor signaling;Signaling events mediated by HDAC Class II;HuR (ELAVL1) binds and stabilizes mRNA;Metabolism of non-coding RNA;Cellular response to heat stress;Nuclear Envelope Breakdown;Mitotic Prophase;M Phase;Nuclear import of Rev protein;Glucose metabolism;Transcriptional regulation by small RNAs;Cell Cycle;Regulation of mRNA stability by proteins that bind AU-rich elements;Interactions of Vpr with host cellular proteins;Glycine, serine, alanine and threonine metabolism;Cell Cycle, Mitotic;Regulation of cytoplasmic and nuclear SMAD2/3 signaling;Sumoylation by RanBP2 regulates transcriptional repression;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Transport of Mature Transcript to Cytoplasm;Signaling events mediated by HDAC Class I;Processing of Capped Intron-Containing Pre-mRNA;Arachidonic acid metabolism;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.216

Intolerance Scores

• loftool: 0.247
• rvis_EVS: -2.15
• rvis_percentile_EVS: 1.47

Haploinsufficiency Scores

• pHI: 0.276
• hipred: Y
• hipred_score: 0.718
• ghis: 0.573

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nup214
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Gene ontology

• Biological process: mitotic cell cycle;mRNA export from nucleus;protein import into nucleus;protein export from nucleus;viral process;regulation of mRNA stability;regulation of nucleocytoplasmic transport;regulation of cell cycle
• Cellular component: nucleus;nuclear pore;nucleoplasm;cytosol;focal adhesion;intracellular membrane-bounded organelle;cytoplasmic side of nuclear pore
• Molecular function: nuclear export signal receptor activity;protein binding;nuclear localization sequence binding;structural constituent of nuclear pore