NFKBIE

protein-coding

NFKB inhibitor epsilon, the group of Ankyrin repeat domain containing

Gene summary

The protein encoded by this gene binds to components of NF-kappa-B, trapping the complex in the cytoplasm and preventing it from activating genes in the nucleus. Phosphorylation of the encoded protein targets it for destruction by the ubiquitin pathway, which activates NF-kappa-B by making it available to translocate to the nucleus. [provided by RefSeq, Sep 2011]

MANE transcript

NM_004556.3

Inheritance

—

ClinVar variants

U:35B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr6:44,258,166-44,265,788

External References & Databases

Ensembl (ENSG00000146232)

Transcript & Mutation Effects

hg38 • Region Span ~7.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NFKBIE variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004556.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			30 clinvar	1 clinvar		31
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	35	2	0	37

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004556.3	RefSeq	NP_004547.3	6	MANE Select
ENST00000619360.6	Ensembl	ENSP00000480216.1	6	MANE Select
ENST00000275015.9	Ensembl	ENSP00000275015.3	6	Standard
ENST00000443607.2	Ensembl	ENSP00000394658.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Adipocytokine signaling pathway - Homo sapiens (human)
T cell receptor signaling pathway - Homo sapiens (human)
B cell receptor signaling pathway - Homo sapiens (human)
Neurotrophin signaling pathway - Homo sapiens (human)
Th17 cell differentiation - Homo sapiens (human)

Biological Process

D-serine transport
cytoplasmic sequestering of transcription factor

Molecular Function

protein binding

Cellular Component

fibrillar center
nucleus
cytoplasm
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000275015
Coding exons: 6
Length: 7598
Individuals with no LoFs: 125620
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125621
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	213	282	0.754	0.0000148	3066
Missense (PolyPhen)		46	87.502	0.5257		946
Synonymous	-0.970	144	130	1.11	0.00000666	1170
Loss of Function	3.28	3	18.0	0.166	7.90e-7	190

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. Inhibits DNA-binding of NF-kappa-B p50-p65 and p50-c-Rel complexes. {ECO:0000269|PubMed:9315679}.;

Recessive Scores

pRec: 0.164

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.896

Gene Damage Prediction

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