NFIL3

protein-coding

nuclear factor, interleukin 3 regulated, the group of Basic leucine zipper proteins

Gene summary

The protein encoded by this gene is a transcriptional regulator that binds as a homodimer to activating transcription factor (ATF) sites in many cellular and viral promoters. The encoded protein represses PER1 and PER2 expression and therefore plays a role in the regulation of circadian rhythm. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2014]

Previous symbols:

IL3BP1

MANE transcript

NM_005384.3

Inheritance

—

ClinVar variants

U:27B:15

Top phenotype

NFIL3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr9:91,408,748-91,424,626

External References & Databases

Ensembl (ENSG00000165030)

Transcript & Mutation Effects

hg38 • Region Span ~15.9 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 NFIL3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 6

NFIL3-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005384.3. 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				6 clinvar	2 clinvar	8
missense			26 clinvar	6 clinvar	1 clinvar	33
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	27	12	3	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005384.3	RefSeq	NP_005375.2	1	MANE Select
ENST00000297689.4	Ensembl	ENSP00000297689.2	1	MANE Select
NM_001289999.2	RefSeq	NP_001276928.1	1	Standard
NM_001290000.2	RefSeq	NP_001276929.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nfil3	Danio rerio	Structure: myeloid lineage restricted progenitor cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

nfil3

Danio rerio

Structure: myeloid lineage restricted progenitor cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

IL-4 Signaling Pathway
Development and heterogeneity of the ILC family

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription, DNA-templated
transcription by RNA polymerase II
immune response
circadian rhythm

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000297689
Coding exons: 1
Length: 14818
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125741
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	172	242	0.710	0.0000133	3031
Missense (PolyPhen)		39	78.291	0.49814		1033
Synonymous	0.00795	97	97.1	0.999	0.00000572	906
Loss of Function	3.03	2	14.4	0.139	8.58e-7	182

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a transcriptional regulator that recognizes and binds to the sequence 5'-[GA]TTA[CT]GTAA[CT]-3', a sequence present in many cellular and viral promoters. Represses transcription from promoters with activating transcription factor (ATF) sites. Represses promoter activity in osteoblasts (By similarity). Represses transcriptional activity of PER1 (By similarity). Represses transcriptional activity of PER2 via the B- site on the promoter (By similarity). Activates transcription from the interleukin-3 promoter in T-cells. Competes for the same consensus-binding site with PAR DNA-binding factors (DBP, HLF and TEF) (By similarity). Component of the circadian clock that acts as a negative regulator for the circadian expression of PER2 oscillation in the cell-autonomous core clock (By similarity). Protects pro-B cells from programmed cell death (By similarity). {ECO:0000250, ECO:0000269|PubMed:1620116, ECO:0000269|PubMed:7565758, ECO:0000269|PubMed:8836190}.;

Recessive Scores

pRec: 0.233

Intolerance Scores

LoFtool: 0.0243
RVIS EVS: -0.03
RVIS percentile EVS: 51.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

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