Encephalopathy, acute, infection-induced, susceptibility to, 9

Summary

Encephalopathy, acute, infection-induced, susceptibility to, 9 (MONDO:0032742) is a disease caused by NUP214 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NUP214 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	encephalopathy, acute, infection-induced, susceptibility to, 9
Mondo ID	MONDO:0032742
OMIM	618426
UMLS	C5193089
MedGen	1673394
Is cancer (heuristic)	no

Also known as: IIAE9

Data availability: 20 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › encephalitis, acute, infection-induced, susceptibility to › encephalopathy, acute, infection-induced, susceptibility to, 9

Related subtypes (6): encephalopathy, acute, infection-induced, susceptibility to, 4, encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 10, encephalitis, acute, infection (viral)-induced, susceptibility to, 11, encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8, immunodeficiency 83, susceptibility to viral infections, encephalitis, acute, infection-induced, susceptibility to, 12

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

20 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 2 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
545116	NM_005085.4(NUP214):c.112C>T (p.Arg38Cys)	NUP214	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
634925	NM_005085.4(NUP214):c.1574del (p.Pro525fs)	NUP214	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2500761	NM_005085.4(NUP214):c.929T>C (p.Ile310Thr)	NUP214	Likely pathogenic	criteria provided, single submitter
634924	NM_005085.4(NUP214):c.1159C>T (p.Pro387Ser)	NUP214	Likely pathogenic	criteria provided, single submitter
1028855	NM_005085.4(NUP214):c.116C>T (p.Ser39Leu)	NUP214	Uncertain significance	criteria provided, single submitter
1048608	NM_005085.4(NUP214):c.1412C>T (p.Ser471Phe)	NUP214	Uncertain significance	criteria provided, single submitter
1048609	NM_005085.4(NUP214):c.3344C>T (p.Thr1115Met)	NUP214	Uncertain significance	criteria provided, multiple submitters, no conflicts
1708051	NM_005085.4(NUP214):c.1129A>G (p.Ile377Val)	NUP214	Uncertain significance	criteria provided, single submitter
2441819	NM_005085.4(NUP214):c.417T>G (p.Phe139Leu)	NUP214	Uncertain significance	criteria provided, single submitter
2504272	NM_005085.4(NUP214):c.4133dup (p.Val1379fs)	NUP214	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065516	NM_005085.4(NUP214):c.655T>G (p.Tyr219Asp)	NUP214	Uncertain significance	criteria provided, single submitter
3065684	NM_005085.4(NUP214):c.5954C>A (p.Ser1985Tyr)	NUP214	Uncertain significance	criteria provided, single submitter
3596490	NM_005085.4(NUP214):c.505C>A (p.Leu169Met)	NUP214	Uncertain significance	criteria provided, multiple submitters, no conflicts
3596491	NM_005085.4(NUP214):c.3952G>A (p.Gly1318Arg)	NUP214	Uncertain significance	criteria provided, single submitter
3596492	NM_005085.4(NUP214):c.5251A>G (p.Ser1751Gly)	NUP214	Uncertain significance	criteria provided, multiple submitters, no conflicts
3596493	NM_005085.4(NUP214):c.6075-4G>A	NUP214	Uncertain significance	criteria provided, single submitter
3777071	NM_005085.4(NUP214):c.515G>A (p.Gly172Asp)	NUP214	Uncertain significance	criteria provided, single submitter
4294314	NM_005085.4(NUP214):c.1291C>T (p.Pro431Ser)	NUP214	Uncertain significance	criteria provided, single submitter
4294315	NM_005085.4(NUP214):c.1681C>G (p.Pro561Ala)	NUP214	Uncertain significance	criteria provided, single submitter
634922	NM_005085.4(NUP214):c.461A>G (p.Asp154Gly)	NUP214	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NUP214	Strong	Autosomal recessive	encephalopathy, acute, infection-induced, susceptibility to, 9	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP214	Orphanet:402014	Acute myeloid leukemia with t(6;9)(p23;q34)
NUP214	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NUP214	HGNC:8064	ENSG00000126883	P35658	Nuclear pore complex protein Nup214	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP214	Nuclear pore complex protein Nup214	Part of the nuclear pore complex.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NUP214	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, Nucleoporin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
monocyte	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP214	246	ubiquitous	marker	left testis, right testis, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP214	2,907

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP214	P35658	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
HuR (ELAVL1) binds and stabilizes mRNA	1	1268.9×	0.006	NUP214
IPs transport between nucleus and cytosol	1	380.7×	0.006	NUP214
IP3 and IP4 transport between cytosol and nucleus	1	380.7×	0.006	NUP214
IP6 and IP7 transport between cytosol and nucleus	1	380.7×	0.006	NUP214
Transport of Ribonucleoproteins into the Host Nucleus	1	356.9×	0.006	NUP214
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	356.9×	0.006	NUP214
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	356.9×	0.006	NUP214
NEP/NS2 Interacts with the Cellular Export Machinery	1	346.1×	0.006	NUP214
Nuclear import of Rev protein	1	335.9×	0.006	NUP214
Vpr-mediated nuclear import of PICs	1	335.9×	0.006	NUP214
Transport of the SLBP independent Mature mRNA	1	326.3×	0.006	NUP214
SUMOylation of SUMOylation proteins	1	326.3×	0.006	NUP214
Transport of the SLBP Dependant Mature mRNA	1	317.2×	0.006	NUP214
Rev-mediated nuclear export of HIV RNA	1	317.2×	0.006	NUP214
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.006	NUP214
SUMOylation of ubiquitinylation proteins	1	292.8×	0.006	NUP214
NS1 Mediated Effects on Host Pathways	1	285.5×	0.006	NUP214
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.006	NUP214
Viral Messenger RNA Synthesis	1	259.6×	0.006	NUP214
SUMOylation of DNA replication proteins	1	248.3×	0.006	NUP214
SUMOylation of RNA binding proteins	1	237.9×	0.006	NUP214
snRNP Assembly	1	211.5×	0.007	NUP214
tRNA processing in the nucleus	1	196.9×	0.007	NUP214
SUMOylation of chromatin organization proteins	1	158.6×	0.008	NUP214
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.008	NUP214
ISG15 antiviral mechanism	1	150.3×	0.008	NUP214
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.008	NUP214
Regulation of HSF1-mediated heat shock response	1	139.3×	0.008	NUP214
HCMV Late Events	1	98.5×	0.011	NUP214
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	NUP214

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of nucleocytoplasmic transport	1	1872.4×	0.004	NUP214
RNA export from nucleus	1	936.2×	0.004	NUP214
protein export from nucleus	1	510.7×	0.004	NUP214
nucleocytoplasmic transport	1	391.9×	0.004	NUP214
mRNA export from nucleus	1	295.6×	0.005	NUP214
protein import into nucleus	1	144.0×	0.008	NUP214
regulation of cell cycle	1	74.6×	0.013	NUP214

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NUP214	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NUP214

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
NUP214	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.