NRF1

Summary

NRF1 (nuclear respiratory factor 1, HGNC:7996) is a protein-coding gene on chromosome 7q32.2, encoding Nuclear respiratory factor 1 (Q16656). Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene.

This gene encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternative splicing results in multiple transcript variants. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for “nuclear factor (erythroid-derived 2)-like 1” which has an official symbol of NFE2L1.

Source: NCBI Gene 4899 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_005011

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7996
Approved symbol	NRF1
Name	nuclear respiratory factor 1
Location	7q32.2
Locus type	gene with protein product
Status	Approved
Aliases	EWG, ALPHA-PAL
Ensembl gene	ENSG00000106459
Ensembl biotype	protein_coding
OMIM	600879
Entrez	4899

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 31 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000223190, ENST00000311967, ENST00000353868, ENST00000393230, ENST00000393232, ENST00000454688, ENST00000477428, ENST00000928007, ENST00000928008, ENST00000928009, ENST00000928010, ENST00000928011, ENST00000928012, ENST00000928013, ENST00000928014, ENST00000928015, ENST00000928016, ENST00000928017, ENST00000928018, ENST00000928019, ENST00000962504, ENST00000962505, ENST00000962506, ENST00000962507, ENST00000962508, ENST00000962509, ENST00000962510, ENST00000962511, ENST00000962512, ENST00000962513, ENST00000962514, ENST00000962515

RefSeq mRNA: 4 — MANE Select: NM_005011 NM_001040110, NM_001293163, NM_001293164, NM_005011

CCDS: CCDS5813, CCDS78273

Canonical transcript exons

ENST00000393232 — 11 exons

Exon	Start	End
ENSE00001514543	129657346	129657574
ENSE00001514544	129611720	129611824
ENSE00003847230	129755018	129757076
ENSE00003890985	129677632	129677758
ENSE00003891594	129711475	129711576
ENSE00003891643	129710374	129710571
ENSE00003891888	129690406	129690546
ENSE00003893539	129717219	129717376
ENSE00003894597	129727241	129727365
ENSE00003894766	129671429	129671543
ENSE00003895839	129709075	129709233

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 88.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0067 / max 84.2817, expressed in 1791 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81040	12.1948	1780
81041	1.8118	1013

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	88.67	gold quality
cerebellar cortex	UBERON:0002129	88.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.39	gold quality
cerebellum	UBERON:0002037	86.50	gold quality
right uterine tube	UBERON:0001302	86.40	gold quality
ventricular zone	UBERON:0003053	86.20	gold quality
apex of heart	UBERON:0002098	86.02	gold quality
adenohypophysis	UBERON:0002196	85.89	gold quality
granulocyte	CL:0000094	85.85	gold quality
ganglionic eminence	UBERON:0004023	85.37	gold quality
sural nerve	UBERON:0015488	85.25	gold quality
gastrocnemius	UBERON:0001388	84.91	gold quality
pituitary gland	UBERON:0000007	84.58	gold quality
muscle of leg	UBERON:0001383	84.48	gold quality
right ovary	UBERON:0002118	84.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.46	gold quality
cortical plate	UBERON:0005343	84.36	gold quality
endocervix	UBERON:0000458	84.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.21	gold quality
body of uterus	UBERON:0009853	83.98	gold quality
right frontal lobe	UBERON:0002810	83.69	gold quality
left ovary	UBERON:0002119	83.58	gold quality
popliteal artery	UBERON:0002250	83.54	gold quality
tibial artery	UBERON:0007610	83.53	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.51	gold quality
lower esophagus mucosa	UBERON:0035834	83.24	gold quality
nerve	UBERON:0001021	83.21	gold quality
tibial nerve	UBERON:0001323	83.21	gold quality
left uterine tube	UBERON:0001303	83.14	gold quality
ectocervix	UBERON:0012249	83.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.37

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0089.2	MAFG::NRF1	Maf-related::NRF
MA0089.3	MAFG::NRF1	Maf-related::NRF
MA0506.1	NRF1	NRF

JASPAR matrix evidence (PMIDs): PMID:9421508, PMID:12533512

miRNA regulators (miRDB)

104 targeting NRF1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3941	99.86	70.54	2735

Literature-anchored findings (GeneRIF, showing 40)

• Insulin resistance and DM associate with reduced expression of multiple nuclear respiratory factor-1 (NRF-1)-dependent genes encoding key enzymes in oxidative metabolism and mitochondrial function (PMID:12832613)
• Overexpression of human nuclear respiratory factor 1 in transgenic mice increases glucose transport capacity in skeletal muscle. (PMID:12958173)
• alpha-Pal/NRF-1 is an essential transcription factor in the regulation of human IAP gene expression (PMID:14747477)
• specifically binds the 21-bp minimal promoter and positively contributes to transcription of the X gene of Hepatitis B virus. (PMID:15452206)
• These findings indicate that a novel function of alpha-Pal/NRF-1 is to regulate neuronal differentiation, and that this function is mediated partly via its downstream IAP gene. (PMID:15992771)
• There is an association between NRF-1 genotypes (rs2402970 and rs6949152 polymorphisms) and the baseline and/or training response of human aerobic capacity. (PMID:18184751)
• These findings support a role for MEF2A as an intermediary in coordinating respiratory chain subunit expression in heart and muscle through a NRF1 –> MEF2A –> COX(H) transcriptional cascade. (PMID:18222924)
• results reveal that especially NRF-1, along with AP-1 and, to a minor extent, an Sp1 site, is essential for human CAPNS1 promoter activity and gene expression (PMID:18234454)
• Data show that NRF-1 is the main transcription factor regulating the expression of TOMM34, and that Sp1 interacts with NRF-1 to stimulate the promoter’s full activity. (PMID:18364745)
• No differences in mRNA levels of genes which mediate the transcriptional of mitochondrial biogenesis (PPARGC1A and NRF1) or in mitochondrial mass between diabetic and control myotubes. (PMID:18719883)
• NRF-1 can also directly interact with poly(ADP-ribose) polymerase 1 (PARP-1) and co-purify the PARP-1.DNA-PK.Ku80.Ku70.topoisomerase IIbeta-containing protein complex. (PMID:19181665)
• Deletion and site-directed mutagenesis combined with in silico transcription factor binding analysis of VSNL1 promoter identified nuclear respiratory factor (NRF)-1/alpha-PAL as a major player in regulating VSNL1 minimal promoter activity. (PMID:19674972)
• Taken together, these results confirm the direct interaction of NRF-1 and ERR alpha with PGC-1 beta, and their participation in mitochondrial biogenesis and respiration. (PMID:20561910)
• Findings indicate that TLR4-dependent NFkappaB and CREB activation co-regulate the NRF1 promoter with NFkappaB intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression. (PMID:20587593)
• This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACCbeta gene promoter in the mammalian heart. (PMID:20599696)
• the obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1 (PMID:20724482)
• Data demonstrated that the polymorphism in TP53 (rs1042522) was associated with type 2 diabetes, and that potential interaction of TP53 (rs1042522) and RAPGEF1 (rs11243444), or NRF1 (rs1882095) increased the risk of type 2 diabetes. (PMID:21146886)
• Single nucleotide polymorphism in NRF1 gene is associated with epithelial ovarian cancer. (PMID:21447778)
• Upon IMS stress, overproduction of reactive oxygen species (ROS) and phosphorylation of AKT triggers estrogen receptor (ER) activity, which further upregulates the transcription of the mitochondrial regulator NRF1 and the IMS protease HTRA2. (PMID:21486948)
• Both NRF-1 and GABP have been linked to the regulation of nuclear-encoded mitochondrial proteins, and the results of this study suggest their expression is coordinated by NRF-1’s activation of the GABPbeta promoter. (PMID:21609478)
• Given that NRF-1 is a key nuclear transcription factor regulating genes involved in mitochondrial activity and biogenesis, these data suggest that diesel exhaust particulate extracts may adversely affect mitochondrial function. (PMID:22105178)
• APE1 is a new coactivator of NRF1, demonstrating an additional regulatory role of APE1 in maintenance of mitochondrial functionality. (PMID:22580151)
• NRF-1 regulates Atp1a1 and Atp1b1 and are important in mediating the energy generation and neuronal activity. (PMID:23048038)
• We verified that NRF-1 positively regulates FAM134C and ENOX1, and negatively regulates C3orf10 in human neuroblastoma IMR-32 cells and primary rat cortical neurons. (PMID:23939472)
• Low NRF1 expression is associated with chronic kidney disease after dialysis. (PMID:24204994)
• The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. (PMID:24875355)
• This study identified a regulatory branch of the mitochondrial unfolded protein response (UPR(mt)), which is mediated by the interplay of SIRT7 and NRF1 and is coupled to cellular energy metabolism and proliferation. (PMID:25792330)
• We show that composite nucleosomes containing mH2A and NRF-1 are stably positioned on gene regulatory regions and can buffer transcriptional noise associated with antiviral responses (PMID:25959814)
• Results present evidence in the support of E2-induced ROS-mediated AKT signalling leading to the activation of NRF-1-regulated cell cycle genes. (PMID:25965299)
• Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway. (PMID:25976310)
• Low NRF1 expression was associated lymphatic metastasis and radio-resistance in nasopharyngeal carcinoma. (PMID:26201446)
• EglN2 associates with the NRF1-PGC1alpha complex and controls mitochondrial function in breast cancer (PMID:26492917)
• NRF1 overexpression attenuated BPDEinduced Sphase arrest via the ATM/Chk2 signaling pathway. (PMID:27035420)
• this study therefore identifies NRF-1 as a novel regulator of HIF-1a. (PMID:27491637)
• NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in Tamoxifen (TAM)-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. (PMID:27515002)
• Chronic kidney disease patients undergoing hemodialysis might be subjected to potential mitochondrial oxidative dysregulation and NRF1 down-regulation. (PMID:28164673)
• CB-5083 decreases viability in multiple myeloma cell lines and patient-derived multiple myeloma cells, including those with background proteasome inhibitor (PI) resistance. CB-5083 has a unique mechanism of action that combines well with PIs, which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI (PMID:28878026)
• HBZ suppresses TDP1 expression by inhibiting NRF-1 function in Adult T-cell leukemia cells. (PMID:28993637)
• NRF1 is more stable in KEAP1(+/+) than in KEAP1(-/-) isogenic cell lines, whereas NRF2 is dramatically stabilized in KEAP1(-/-) cells. (PMID:29255090)
• By Ras via MEK/ERK/NRF1/Atg7 signaling pathways. (PMID:29908161)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrf1	ENSDARG00000000018
mus_musculus	Nrf1	ENSMUSG00000058440
rattus_norvegicus	Nrf1	ENSRNOG00000008752
drosophila_melanogaster	ewg	FBGN0005427
drosophila_melanogaster	ova	FBGN0032197

Protein

Protein identifiers

Nuclear respiratory factor 1 — Q16656 (reviewed: Q16656)

Alternative names: Alpha palindromic-binding protein

All UniProt accessions (2): Q16656, C9JP85

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene. Links the transcriptional modulation of key metabolic genes to cellular growth and development. Implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication.

Subunit / interactions. Homodimer. Binds DNA as a dimer. Interacts with PPRC1.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed with strongest expression in skeletal muscle.

Post-translational modifications. Phosphorylation enhances DNA binding.

Similarity. Belongs to the NRF1/Ewg family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q16656-1	Long	yes
Q16656-2	Short
Q16656-3	3
Q16656-4	4

RefSeq proteins (4): NP_001035199, NP_001280092, NP_001280093, NP_005002* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019525	Nrf1_NLS/DNA-bd_dimer	Domain
IPR039142	NRF1/Ewg	Family

Pfam: PF10491

UniProt features (34 total): helix 11, modified residue 5, strand 5, splice variant 3, region of interest 3, sequence conflict 2, chain 1, DNA-binding region 1, cross-link 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8K4L	X-RAY DIFFRACTION	2.1
8K3D	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16656-F1	58.73	0.17

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 (6): 52, 139, 39, 44, 46, 47

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)

MSigDB gene sets: 189 (showing top): RNGTGGGC_UNKNOWN, TGCGCANK_UNKNOWN, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AP2_Q3, GCM_RING1, ATF1_Q6, chr7q32, MARTIN_VIRAL_GPCR_SIGNALING_UP, KEGG_HUNTINGTONS_DISEASE, MODULE_123, MYOD_Q6, HIF1_Q3, MYB_Q3, GCM_TEC

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (7): 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 activator activity, RNA polymerase II-specific (GO:0001228), protein homodimerization activity (GO:0042803), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Mitochondrial biogenesis	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
identical protein binding	1
protein dimerization activity	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRF1	PPARGC1A	Q9UBK2	998
NRF1	TFAM	Q00059	977
NRF1	FOXO3	O43524	933
NRF1	PPARGC1B	Q86YN6	916
NRF1	SIRT1	Q96EB6	816
NRF1	GABPA	Q06546	768
NRF1	PPP1R15B	Q5SWA1	717
NRF1	ESRRA	P11474	706
NRF1	EIF2S2	P20042	703
NRF1	EIF2S1	P05198	700
NRF1	GABPB1	Q06547	697
NRF1	EIF5	P55010	686
NRF1	SIRT7	Q9NRC8	679
NRF1	EIF1	P41567	639
NRF1	PPARG	P37231	629

IntAct

35 interactions, top by confidence:

A	B	Type	Score
NRF1	FHL2	psi-mi:“MI:0915”(physical association)	0.670
FHL2	NRF1	psi-mi:“MI:0915”(physical association)	0.670
NRF1	SP4	psi-mi:“MI:0915”(physical association)	0.560
NRF1	TRAF2	psi-mi:“MI:0915”(physical association)	0.560
POGZ	NRF1	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	NRF1	psi-mi:“MI:0915”(physical association)	0.560
NRF1	POGZ	psi-mi:“MI:0915”(physical association)	0.560
SP4	NRF1	psi-mi:“MI:0915”(physical association)	0.560
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
WDR59	EPB41L2	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
SIRT7	NRF1	psi-mi:“MI:0915”(physical association)	0.520
DYNLL1	SHMT2	psi-mi:“MI:0914”(association)	0.510
DYNLL2	SHMT2	psi-mi:“MI:0914”(association)	0.510
CCND1	NRF1	psi-mi:“MI:0915”(physical association)	0.510
NRF1	E7	psi-mi:“MI:0915”(physical association)	0.370
PB1	NRF1	psi-mi:“MI:0915”(physical association)	0.370
NRF1	PB1	psi-mi:“MI:0915”(physical association)	0.370
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
WDR59	HDAC3	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): NRF1 (Two-hybrid), SP4 (Two-hybrid), TRAF2 (Two-hybrid), POGZ (Two-hybrid), PLXDC1 (Two-hybrid), NRF1 (Affinity Capture-MS), NRF1 (Affinity Capture-MS), NRF1 (Affinity Capture-MS), NRF1 (Affinity Capture-MS), NRF1 (Affinity Capture-MS), NRF1 (Affinity Capture-MS), NRF1 (Affinity Capture-RNA), NRF1 (Co-localization), NRF1 (Co-localization), NRF1 (Co-localization)

ESM2 similar proteins: A0JMF8, A2RSY1, A6QLW9, B1WAV2, B2GV50, O60271, O75069, O77627, P05412, P05627, P0C090, P17325, P22670, P48377, P48378, P48379, P48380, P48381, P56432, Q0V989, Q0V9K5, Q16656, Q32NR3, Q3KR73, Q499B3, Q49GP3, Q4R3I8, Q4R3Z4, Q4V872, Q4VGL6, Q58A65, Q5EAP5, Q5EY87, Q5RDR2, Q5RJA1, Q5TC82, Q62739, Q66IV1, Q6NRE7, Q6NUC6

Diamond homologs: Q04073, Q16656, Q24312, Q90X44, Q9WU00, Q62792

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
PRKAA1	up-regulates	NRF1
PPARGC1A	“up-regulates activity”	NRF1
NRF1	“up-regulates quantity by expression”	FMR1	“transcriptional regulation”
NRF1	“up-regulates quantity by expression”	SLC46A1	“transcriptional regulation”
NRF1	“up-regulates quantity by expression”	SPAST	“transcriptional regulation”
NRF1	“up-regulates quantity by expression”	RETREG3	“transcriptional regulation”
NRF1	“up-regulates quantity by expression”	ENOX1	“transcriptional regulation”
NRF1	“down-regulates quantity by repression”	BRK1	“transcriptional regulation”
NRF1	up-regulates	ENOX1
NRF1	up-regulates	RETREG3
NRF1	“up-regulates quantity by expression”	TFB2M	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005204 (7:129742466 T>A), RS1000009633 (7:129756533 CTCTG>C), RS1000017301 (7:129621924 A>G), RS1000044458 (7:129631204 T>G), RS1000088967 (7:129674015 C>T), RS1000090774 (7:129614558 G>A), RS1000099734 (7:129657299 A>G,T), RS1000107076 (7:129749663 A>T), RS1000114484 (7:129613364 G>T), RS1000170065 (7:129672930 G>A), RS1000171515 (7:129718994 T>C), RS1000199787 (7:129724279 C>T), RS1000209702 (7:129669016 C>T), RS1000212846 (7:129698591 G>A,T), RS1000245489 (7:129698990 T>C)

Disease associations

OMIM: gene MIM:600879 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression	5
Resveratrol	increases expression, affects cotreatment, decreases expression, increases reaction, decreases reaction	4
Arsenic	decreases expression, increases abundance, affects methylation, increases expression	3
Benzo(a)pyrene	decreases reaction, increases abundance, increases reaction, affects methylation, decreases expression	3
Estradiol	decreases reaction, increases expression	3
Hydrogen Peroxide	affects expression, decreases expression, affects response to substance, decreases reaction	3
Doxorubicin	decreases expression, decreases reaction, affects reaction	2
Formaldehyde	decreases expression	2
T-2 Toxin	affects reaction, decreases expression, affects binding, increases reaction	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	increases methylation	2
FR900359	decreases phosphorylation	1
flumetralin	increases expression	1
uranyl acetate	affects expression	1
cobaltiprotoporphyrin	increases expression, decreases reaction	1
di-n-octyl phthalate	decreases expression	1
acadesine	decreases expression, decreases reaction, increases expression	1
8-bromocyclic GMP	increases expression, decreases reaction	1
afimoxifene	increases expression, decreases reaction	1
sulforaphane	increases expression	1
butylbenzyl phthalate	decreases expression	1
tin protoporphyrin IX	decreases reaction, increases expression, increases reaction	1
dimethoxyethyl phthalate	decreases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression, decreases reaction, decreases phosphorylation	1
polyoxyethyleneamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one	decreases reaction, increases expression	1
propham	increases expression	1
mepanipyrim	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4Y1	SEES3-1V human NRF1, clone1	Embryonic stem cell	Male
CVCL_A4Y2	SEES3-1V human NRF1, clone2	Embryonic stem cell	Male
CVCL_A4Y3	SEES3-1V human NRF1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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