NFIL3

Summary

NFIL3 (nuclear factor, interleukin 3 regulated, HGNC:7787) is a protein-coding gene on chromosome 9q22.31, encoding Nuclear factor interleukin-3-regulated protein (Q16649). 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.

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.

Source: NCBI Gene 4783 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 37 total
• Transcription factor: yes — 41 downstream targets (CollecTRI)
• MANE Select transcript: NM_005384

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7787
Approved symbol	NFIL3
Name	nuclear factor, interleukin 3 regulated
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	E4BP4, NFIL3A, NF-IL3A
Ensembl gene	ENSG00000165030
Ensembl biotype	protein_coding
OMIM	605327
Entrez	4783

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000297689, ENST00000718345, ENST00000876779, ENST00000876780, ENST00000876781, ENST00000876782, ENST00000876783, ENST00000938983, ENST00000938984, ENST00000968872, ENST00000968873, ENST00000968874, ENST00000968875, ENST00000968876

RefSeq mRNA: 3 — MANE Select: NM_005384 NM_001289999, NM_001290000, NM_005384

CCDS: CCDS6690

Canonical transcript exons

ENST00000297689 — 2 exons

Exon	Start	End
ENSE00001292518	91423640	91423832
ENSE00004034832	91409045	91410906

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7387 / max 887.5541, expressed in 1774 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101377	18.1803	1770
101376	1.1768	524
101372	0.1893	49
101371	0.1477	57
101373	0.0446	17

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	98.93	gold quality
pericardium	UBERON:0002407	98.11	gold quality
mucosa of stomach	UBERON:0001199	98.05	gold quality
left uterine tube	UBERON:0001303	97.65	gold quality
cartilage tissue	UBERON:0002418	97.17	gold quality
popliteal artery	UBERON:0002250	96.99	gold quality
tibial artery	UBERON:0007610	96.98	gold quality
omental fat pad	UBERON:0010414	96.92	gold quality
peritoneum	UBERON:0002358	96.89	gold quality
stromal cell of endometrium	CL:0002255	96.61	gold quality
periodontal ligament	UBERON:0008266	96.32	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.25	gold quality
heart right ventricle	UBERON:0002080	95.87	gold quality
endocervix	UBERON:0000458	95.75	gold quality
decidua	UBERON:0002450	95.74	gold quality
left ovary	UBERON:0002119	95.57	gold quality
aorta	UBERON:0000947	95.51	gold quality
gastrocnemius	UBERON:0001388	95.32	gold quality
right ovary	UBERON:0002118	95.05	gold quality
cortical plate	UBERON:0005343	95.05	gold quality
ectocervix	UBERON:0012249	94.94	gold quality
tibial nerve	UBERON:0001323	94.62	gold quality
upper lobe of left lung	UBERON:0008952	94.45	gold quality
blood	UBERON:0000178	94.37	gold quality
ganglionic eminence	UBERON:0004023	94.30	gold quality
islet of Langerhans	UBERON:0000006	94.22	gold quality
upper lobe of lung	UBERON:0008948	94.14	gold quality
cauda epididymis	UBERON:0004360	94.13	gold quality
lower lobe of lung	UBERON:0008949	94.13	gold quality
monocyte	CL:0000576	94.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	7.28
E-MTAB-6075	no	243.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

41 targets.

Target	Regulation
ABCB1	Unknown
APP	Unknown
AREG	Unknown
ARNT
BCL2L1	Repression
BMP4
CD28
CD3E
CD40LG
CD86
CYP3A4	Repression
CYP7A1	Repression
DLST
EHMT2
EREG	Unknown
FGF21	Repression
GADD45B
HPGD	Unknown
IFNG	Unknown
IL10	Activation
IL12B	Repression
IL13	Repression
IL1B	Repression
IL2RB
IL3	Activation
IL33
PER1	Repression
PER2
PGR	Unknown
PHEX	Unknown

JASPAR motifs

Motif	Name	Family
MA0025.1	NFIL3	CEBP-related
MA0025.2	NFIL3	CEBP-related
MA0025.3	NFIL3	CEBP-related

JASPAR matrix evidence (PMIDs): PMID:1620116, PMID:9122243

Upstream regulators (CollecTRI, top): GATA1, MYC, NR3C1, PTEN

miRNA regulators (miRDB)

36 targeting NFIL3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-216B-3P	98.55	67.19	1223

Literature-anchored findings (GeneRIF, showing 29)

• This report demonstrates that GC-mediated upregulation of the bZIP transcriptional repressor gene, E4BP4, is dependent on [Ca2+]i levels, and correlates with GC-evoked apoptosis of GC-sensitive CEM-C7-14 cells. (PMID:16630563)
• E4BP4 has a role as osteoblast transcriptional repressor in inhibiting both Runx2 and Osterix in myeloma bone disease (PMID:18829486)
• Identification of adjacent binding sites for the YY1 and E4BP4 transcription factors in the PrP (Prion) gene promoter. (PMID:19129193)
• Conclude that E4BP4 plays as a survival factor in heart and E4BP4 is essential for proper embryonic heart development. (PMID:20186462)
• The clock-regulated and immune system modulator transcription factor E4BP4/ NFIL3 likely regulates the expression of both appb in zebrafish and APP in humans. (PMID:22947103)
• G9a mediates E4BP4-dependent suppression of hepatic Fgf21 by enhancing histone methylation (H3K9me2) of the Fgf21 promoter (PMID:23283977)
• Data indicate that E4BP4 can inhibit CD40L expression through epigenetic modifications in the promoter region of CD40L. (PMID:23340290)
• NFIL3 alters cancer cell behavior and FOXO function by acting on chromatin to restrict the menu of FOXO target genes (PMID:23630076)
• NFIL3 plays a neuroprotective role in neurons and constitutes a potential therapeutic target for neurodegeneration. (PMID:24280221)
• Results conclude that the transcriptional repressor E4BP4 plays a role in repressing epigenetically regulated SOSTDC1 expression in breast cancer cells, which can be reverted by E4BP4 silencing. (PMID:25338303)
• E4BP4 and BIM regulation correlated with that of RCAN1-1. A putative GRE and four EBPREs were identified within 1500bp upstream from the transcription start site of RCAN1-1 (PMID:26102033)
• glucocorticoid-mediated transactivating pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3 (PMID:26880402)
• Here we review the regulatory mechanisms of E4BP4 engaging in not only the biological function but also the development of immune-mediated diseases, paving the way for future therapies (PMID:28365317)
• STAT3/NFIL3 axis-inhibited apoptosis is a novel mechanism of chemotherapy resistance in choriocarcinoma. With the suppression of STAT3/NFIL3 axis and apoptosis induction, RA is a potential agent or lead candidate for improving chemotherapy. (PMID:29215740)
• Our results indicate that the action of E4bp4 in NK cells is highly regulated and can potentially be strongly influenced by extrinsic stimuli (PMID:29311361)
• data provide evidence that E4BP4 attenuates RASSF8-mediated anti-proliferation and apoptosis, shedding mechanistic insights into RASSF8 down-regulation in breast cancers. (PMID:29467226)
• We propose that E4BP4, being the critical component for the regulation of the above signaling processes, may serve as a novel therapeutic target for Heart failure , and scientific investigations are merited in this direction. (PMID:29856483)
• E4BP4 contribute to enhance the GCs sensitivity. (PMID:30153899)
• Depletion of E4BP4 inhibits cancer growth, reduces hepcidin secretion, and reduces G9a nuclear transportation. Iron homeostasis and tumor growth in thyroid cancer may be regulated by an E4BP4-dependent epigenetic mechanism. (PMID:30250199)
• our observations suggest that the NFIL3/PrPc axis, through regulating lamellipodium formation and cell mobility via JNK signaling, plays a critical role in lung cancer invasiveness and metastasis. (PMID:31477838)
• NFIL3 is highly expressed in osteosarcoma tissues and thus promotes the proliferation, migration, and invasion of osteosarcoma cells. NFIL3 is potential to become a new target for development of novel treatment strategies of osteosarcoma. (PMID:31886210)
• E4BP4-mediated inhibition of T follicular helper cell differentiation is compromised in autoimmune diseases. (PMID:32191636)
• Diurnal Rhythmicity Programs of Microbiota and Transcriptional Oscillation of Circadian Regulator, NFIL3. (PMID:33013924)
• NFIL3 and its immunoregulatory role in rheumatoid arthritis patients. (PMID:36439145)
• A Potential Role of NFIL3 in Atherosclerosis. (PMID:37741601)
• NFIL3 aggravates human coronary artery endothelial cell injury by promoting ITGAM transcription in Kawasaki disease. (PMID:37933872)
• The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update. (PMID:38193973)
• Structural basis for specific DNA sequence recognition by the transcription factor NFIL3. (PMID:38382670)
• Knockdown of NFIL3 modulates the AMPK pathway to suppress excessive cell proliferation, inflammation, and migration in rheumatoid arthritis. (PMID:39175280)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfil3	ENSDARG00000042977
mus_musculus	Nfil3	ENSMUSG00000056749
rattus_norvegicus	Nfil3	ENSRNOG00000011668
drosophila_melanogaster	vri	FBGN0016076
caenorhabditis_elegans		WBGENE00000220

Paralogs (1): NFILZ (ENSG00000268480)

Protein

Protein identifiers

Nuclear factor interleukin-3-regulated protein — Q16649 (reviewed: Q16649)

Alternative names: E4 promoter-binding protein 4, Interleukin-3 promoter transcriptional activator, Interleukin-3-binding protein 1, Transcriptional activator NF-IL3A

All UniProt accessions (1): Q16649

UniProt curated annotations — full annotation on UniProt →

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. Represses transcriptional activity of PER1. Represses transcriptional activity of PER2 via the B-site on the promoter. 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). Component of the circadian clock that acts as a negative regulator for the circadian expression of PER2 oscillation in the cell-autonomous core clock. Protects pro-B cells from programmed cell death. Represses the transcription of CYP2A5. Positively regulates the expression and activity of CES2 by antagonizing the repressive action of NR1D1 on CES2. Required for the development of natural killer cell precursors.

Subunit / interactions. Homodimer. Binds DNA as a dimer. Interacts with DR1. Interacts with PER2 and CRY2. Interacts with NR0B2. Interacts with MYSM1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in bladder stomach, thyroid, spinal cord, lymph node, trachea, adrenal gland, bone marrow and muscle.

Induction. Up-regulated by PHA or TPA.

Similarity. Belongs to the bZIP family. NFIL3 subfamily.

RefSeq proteins (3): NP_001276928, NP_001276929, NP_005375* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR010533	Vert_IL3-reg_TF	Domain
IPR016743	NFIL3/E4BP4	Family
IPR046347	bZIP_sf	Homologous_superfamily
IPR047106	NFIL3-like_bZIP	Domain
IPR047229	NFIL3-like	Family

Pfam: PF06529, PF07716

UniProt features (41 total): cross-link 19, region of interest 5, mutagenesis site 4, sequence conflict 3, helix 3, compositionally biased region 3, modified residue 2, chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8K86	X-RAY DIFFRACTION	2.06
8K8A	X-RAY DIFFRACTION	2.07
8K89	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16649-F1	57.65	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (21): 301, 353, 24, 214, 219, 219, 306, 314, 326, 332, 337, 350, 360, 394, 401, 406, 412, 419, 424, 434 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
330	interacts with dr1 and partially affects transcriptional repression; when associated with e-332.
330	does not interact with dr1 and drastically affects transcriptional repression; when associated with e-332.
332	interacts with dr1 and partially affects transcriptional repression; when associated with e-330.
332	does not interact with dr1 and drastically affects transcriptional repression; when associated with e-330.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 448 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_CIRCADIAN_RHYTHM, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, MCLACHLAN_DENTAL_CARIES_UP, LU_IL4_SIGNALING, MODULE_255, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, MENSE_HYPOXIA_UP, HALMOS_CEBPA_TARGETS_UP, MODULE_317, TGACCTY_ERR1_Q2

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), natural killer cell differentiation (GO:0001779), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), immune response (GO:0006955), circadian rhythm (GO:0007623), positive regulation of gene expression (GO:0010628), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), cellular response to interleukin-4 (GO:0071353), DNA-templated transcription (GO:0006351), rhythmic process (GO:0048511)

GO Molecular Function (8): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), RNA polymerase II transcription regulator complex (GO:0090575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	4
regulation of DNA-templated transcription	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of gene expression	2
gene expression	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
lymphocyte differentiation	1
natural killer cell activation	1
regulation of RNA biosynthetic process	1
immune system process	1
response to stimulus	1
rhythmic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
response to interleukin-4	1
cellular response to cytokine stimulus	1
RNA biosynthetic process	1
biological_process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription regulator activity	1
protein binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFIL3	NR1D1	P20393	964
NFIL3	PER2	O15055	955
NFIL3	PER3	P56645	955
NFIL3	BMAL1	O00327	946
NFIL3	CRY1	Q16526	941
NFIL3	NPAS2	Q99743	930
NFIL3	NR1D2	Q14995	924
NFIL3	RORA	P35397	904
NFIL3	RORB	Q92753	903
NFIL3	BHLHE40	O14503	902
NFIL3	BHLHE41	Q9C0J9	893
NFIL3	RORC	P51449	887
NFIL3	CLOCK	O15516	866
NFIL3	CRY2	Q49AN0	859
NFIL3	TIMELESS	Q9UNS1	753

IntAct

71 interactions, top by confidence:

A	B	Type	Score
NFIL3	NFIL3	psi-mi:“MI:0407”(direct interaction)	0.730
NFIL3	AMOTL2	psi-mi:“MI:0915”(physical association)	0.670
DDIT3	NFIL3	psi-mi:“MI:0407”(direct interaction)	0.620
ATF1	NFIL3	psi-mi:“MI:0407”(direct interaction)	0.590
CREB1	NFIL3	psi-mi:“MI:0407”(direct interaction)	0.590
NFIL3	ATF1	psi-mi:“MI:0407”(direct interaction)	0.590
NFIL3	CREB1	psi-mi:“MI:0407”(direct interaction)	0.590
NFIL3	TRAF2	psi-mi:“MI:0915”(physical association)	0.560
AMOTL2	NFIL3	psi-mi:“MI:0915”(physical association)	0.560
NFIL3	AMOTL2	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	NFIL3	psi-mi:“MI:0915”(physical association)	0.560
MDV005	NFIL3	psi-mi:“MI:0407”(direct interaction)	0.560
HSF2BP	NFIL3	psi-mi:“MI:0915”(physical association)	0.560
NFIL3	RINT1	psi-mi:“MI:0915”(physical association)	0.560
NFIL3	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
PDE9A	NFIL3	psi-mi:“MI:0915”(physical association)	0.560
NFIL3	PIH1D2	psi-mi:“MI:0915”(physical association)	0.560
NFIL3	STK40	psi-mi:“MI:0914”(association)	0.530
NFIL3		psi-mi:“MI:0915”(physical association)	0.500
	NFIL3	psi-mi:“MI:0914”(association)	0.500

BioGRID (48): TRAF2 (Two-hybrid), AMOTL2 (Two-hybrid), NFIL3 (Two-hybrid), AMOTL2 (Two-hybrid), NFIL3 (Affinity Capture-MS), NFIL3 (Reconstituted Complex), RFWD2 (Affinity Capture-MS), STK40 (Affinity Capture-MS), CREB1 (Affinity Capture-MS), ATF1 (Affinity Capture-MS), NFIL3 (Affinity Capture-MS), NFIL3 (Affinity Capture-MS), NFIL3 (Negative Genetic), NFIL3 (Affinity Capture-RNA), NFIL3 (Affinity Capture-MS)

ESM2 similar proteins: B0FZN7, B0FZN8, B0FZN9, B0FZP0, B0FZP1, B0FZP2, B0FZP3, O08750, O60381, P01105, P04150, P08235, P10157, P19102, P32314, P46200, Q08D88, Q0P4X6, Q16649, Q1LXZ9, Q29131, Q2KJ34, Q3UPW2, Q3YC04, Q4JM28, Q4V7E1, Q5DTV4, Q5FW38, Q5HYM0, Q5R7I3, Q5R9P5, Q5WM45, Q62661, Q66J36, Q66J77, Q68EL6, Q6NYU3, Q6XLJ0, Q8AYI2, Q8K402

Diamond homologs: A0A5F9ZHS7, O08750, P16443, P41224, P97516, Q08D88, Q10586, Q10587, Q16534, Q16649, Q32PF6, Q5FW38, Q60925, Q64709, Q66J36, Q68EL6, Q6IMZ0, Q8BW74, Q90Z72, Q92172, Q94126, Q9JLC6

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
NFIL3	“down-regulates quantity by repression”	SOSTDC1	“transcriptional regulation”
NFIL3	“down-regulates quantity by repression”	CYP3A4	“transcriptional regulation”
PTEN	“up-regulates quantity by expression”	NFIL3	“transcriptional regulation”
NR3C1	“up-regulates quantity by expression”	NFIL3	“transcriptional regulation”
NFIL3	“down-regulates quantity by repression”	PER1	“transcriptional regulation”
KRAS	up-regulates	NFIL3
NFIL3	up-regulates	Survival
IL3	up-regulates	NFIL3
NFIL3	down-regulates	Apoptosis
NFIL3	down-regulates	Cell_death
NFIL3	“up-regulates activity”	NFIL3	binding
NFIL3	“up-regulates quantity by expression”	IL3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

37 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

314 predictions. Top by Δscore:

Variant	Effect	Δscore
9:91410903:TTAT:T	acceptor_gain	1.0000
9:91410904:TAT:T	acceptor_gain	1.0000
9:91410905:ATCT:A	acceptor_loss	1.0000
9:91410906:TCTGC:T	acceptor_loss	1.0000
9:91410907:C:CC	acceptor_gain	1.0000
9:91410912:A:AC	acceptor_gain	1.0000
9:91410915:C:CT	acceptor_gain	1.0000
9:91410916:A:AC	acceptor_gain	1.0000
9:91410916:A:C	acceptor_gain	1.0000
9:91423634:GCTTA:G	donor_loss	1.0000
9:91423635:CTTAC:C	donor_loss	1.0000
9:91423636:TTAC:T	donor_loss	1.0000
9:91423637:TACC:T	donor_loss	1.0000
9:91423638:A:AC	donor_gain	1.0000
9:91423638:A:C	donor_loss	1.0000
9:91423639:C:CC	donor_gain	1.0000
9:91423639:C:G	donor_loss	1.0000
9:91410902:GTTAT:G	acceptor_gain	0.9900
9:91410905:AT:A	acceptor_gain	0.9900
9:91410908:T:A	acceptor_loss	0.9900
9:91410910:CAA:C	acceptor_gain	0.9900
9:91410911:A:T	acceptor_gain	0.9900
9:91410912:A:C	acceptor_gain	0.9900
9:91410916:A:T	acceptor_gain	0.9900
9:91423638:AC:A	donor_gain	0.9900
9:91423639:CC:C	donor_gain	0.9900
9:91410836:T:TA	donor_gain	0.9800
9:91410920:A:AC	acceptor_gain	0.9800
9:91422557:C:CA	donor_gain	0.9800
9:91423639:CCGT:C	donor_gain	0.9800

AlphaMissense

3040 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:91409755:A:G	L327P	1.000
9:91409757:C:A	K326N	1.000
9:91409757:C:G	K326N	1.000
9:91409759:T:C	K326E	1.000
9:91410370:A:G	L122P	1.000
9:91410379:A:G	L119P	1.000
9:91410412:A:G	L108P	1.000
9:91410421:A:G	L105P	1.000
9:91410439:A:G	L99P	1.000
9:91410442:T:A	D98V	1.000
9:91410442:T:C	D98G	1.000
9:91410442:T:G	D98A	1.000
9:91410443:C:G	D98H	1.000
9:91410451:C:G	R95P	1.000
9:91410454:C:G	R94P	1.000
9:91410455:G:A	R94C	1.000
9:91410455:G:T	R94S	1.000
9:91410456:C:A	K93N	1.000
9:91410456:C:G	K93N	1.000
9:91410458:T:C	K93E	1.000
9:91410463:C:G	R91P	1.000
9:91410463:C:T	R91H	1.000
9:91410464:G:A	R91C	1.000
9:91410464:G:C	R91G	1.000
9:91410464:G:T	R91S	1.000
9:91410466:G:A	S90F	1.000
9:91410467:A:G	S90P	1.000
9:91410468:T:A	R89S	1.000
9:91410468:T:G	R89S	1.000
9:91410469:C:G	R89T	1.000

dbSNP variants (sampled 300 via entrez): RS1000031510 (9:91475649 T>G), RS1000077777 (9:91437018 A>C,G), RS1000130320 (9:91429834 A>G), RS1000160505 (9:91447354 T>C), RS1000161092 (9:91454427 A>G), RS1000230410 (9:91423372 G>A,C,T), RS1000247120 (9:91441860 G>A), RS1000272669 (9:91482474 C>G,T), RS1000318723 (9:91471405 G>C), RS1000319447 (9:91442233 G>T), RS1000337862 (9:91417298 A>G), RS1000366993 (9:91460336 G>A), RS1000379169 (9:91467056 C>G,T), RS1000381759 (9:91409790 A>C), RS1000447640 (9:91448020 A>G,T)

Disease associations

OMIM: gene MIM:605327 | disease phenotypes: MIM:250950

GenCC curated gene-disease

Mondo (1): 3-methylglutaconic aciduria type 1 (MONDO:0009610)

Orphanet (1): 3-methylglutaconic aciduria type 1 (Orphanet:67046)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001725_100	Inflammatory bowel disease	4.000000e-09
GCST002815_1	Bipolar disorder (inflammation and infection response interaction)	8.000000e-06
GCST008362_117	Birth weight	2.000000e-08
GCST008363_116	Offspring birth weight	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007037	cytomegalovirus seropositivity
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562801	3-Methylglutaconic Aciduria, Type I (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

102 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects methylation	4
Vehicle Emissions	affects cotreatment, affects expression, increases reaction, decreases expression, decreases reaction	3
Cisplatin	affects expression, affects cotreatment, decreases expression, increases expression	3
Particulate Matter	decreases expression, decreases reaction, increases abundance, affects expression, increases reaction	3
nickel sulfate	increases expression	2
Acetaminophen	increases expression	2
Cadmium	decreases expression, increases expression	2
Cannabidiol	affects cotreatment, decreases expression, increases expression	2
Estradiol	decreases expression, increases expression	2
Progesterone	increases expression	2
Silicon Dioxide	decreases expression	2
Tamoxifen	decreases expression, affects expression, affects cotreatment	2
Valproic Acid	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation, increases expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
moringin	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
geraniol	increases expression	1
lead acetate	decreases expression	1
methylselenic acid	affects expression	1
kojic acid	increases expression	1
arsenite	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4N5	SEES3-1V human NFIL3, clone1	Embryonic stem cell	Male
CVCL_A4N6	SEES3-1V human NFIL3, clone2	Embryonic stem cell	Male
CVCL_A4N7	SEES3-1V human NFIL3, clone3	Embryonic stem cell	Male
CVCL_XQ95	HAP1 NFIL3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan