NFXL1

gene
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Also known as HOZFP

Summary

NFXL1 (nuclear transcription factor, X-box binding like 1, HGNC:18726) is a protein-coding gene on chromosome 4p12, encoding NF-X1-type zinc finger protein NFXL1 (Q6ZNB6).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of DNA-templated transcription. Located in membrane.

Source: NCBI Gene 152518 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 72 total
  • Druggable target: yes
  • MANE Select transcript: NM_001278624

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:18726
Approved symbolNFXL1
Namenuclear transcription factor, X-box binding like 1
Location4p12
Locus typegene with protein product
StatusApproved
AliasesHOZFP
Ensembl geneENSG00000170448
Ensembl biotypeprotein_coding
OMIM620488
Entrez152518

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000329043, ENST00000381538, ENST00000464756, ENST00000502448, ENST00000507131, ENST00000507489, ENST00000508115, ENST00000511452, ENST00000906325, ENST00000927224, ENST00000927225

RefSeq mRNA: 3 — MANE Select: NM_001278624 NM_001278623, NM_001278624, NM_152995

CCDS: CCDS3478

Canonical transcript exons

ENST00000507489 — 23 exons

ExonStartEnd
ENSE000020293644791436547914583
ENSE000034591754785109547851148
ENSE000034775794787852547878665
ENSE000034955714786284647862915
ENSE000034983404788549847885657
ENSE000035012644791396947914205
ENSE000035024894785185647851942
ENSE000035067954789875747898857
ENSE000035159394787909647879117
ENSE000035169584790523747905346
ENSE000035571324790319347903323
ENSE000035594434789061347890703
ENSE000035597774785505947855163
ENSE000035643274789895947899120
ENSE000035870704787512747875293
ENSE000035891304788434647884437
ENSE000036185864789418047894302
ENSE000036360574789937047899548
ENSE000036448414789652347896647
ENSE000036476444789796747898081
ENSE000036489934788587947885999
ENSE000036575374784724047848336
ENSE000036896444791082447910994

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 97.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3563 / max 186.3378, expressed in 1766 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
520467.84581698
520452.67201307
520472.42101188
520430.162745
520440.145047
520420.109833

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
secondary oocyteCL:000065597.87gold quality
oocyteCL:000002395.55gold quality
epithelial cell of pancreasCL:000008393.38gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099192.91gold quality
spermCL:000001988.66gold quality
corpus epididymisUBERON:000435987.75gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047386.94gold quality
calcaneal tendonUBERON:000370186.46gold quality
cartilage tissueUBERON:000241886.31gold quality
ventricular zoneUBERON:000305385.04gold quality
body of pancreasUBERON:000115084.71gold quality
testisUBERON:000047384.14gold quality
left testisUBERON:000453383.73gold quality
endothelial cellCL:000011583.62silver quality
right testisUBERON:000453483.50gold quality
bone marrow cellCL:000209283.05gold quality
pancreasUBERON:000126482.87gold quality
endometriumUBERON:000129582.81gold quality
right lobe of liverUBERON:000111482.73gold quality
caput epididymisUBERON:000435882.58gold quality
colonic epitheliumUBERON:000039781.98gold quality
right lobe of thyroid glandUBERON:000111981.81gold quality
oviduct epitheliumUBERON:000480481.77gold quality
left lobe of thyroid glandUBERON:000112081.57gold quality
thyroid glandUBERON:000204681.55gold quality
right uterine tubeUBERON:000130281.30gold quality
tendonUBERON:000004381.28gold quality
endocervixUBERON:000045881.14gold quality
pancreatic ductal cellCL:000207981.02silver quality
body of uterusUBERON:000985381.02gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes6.10
E-ENAD-17no247.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting NFXL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-126-5P100.0072.713180
HSA-MIR-4682100.0068.891258
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-6833-3P100.0070.633197
HSA-MIR-4768-5P100.0069.492861
HSA-MIR-3646100.0073.565283
HSA-MIR-5692B100.0071.322622
HSA-MIR-5692C100.0071.322622
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-428299.9975.366408
HSA-MIR-196A-1-3P99.9972.152772
HSA-MIR-548P99.9872.253784
HSA-MIR-60799.9773.625593
HSA-MIR-302C-5P99.9772.563642
HSA-MIR-570-3P99.9672.414910
HSA-MIR-365899.9673.874379
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-144-3P99.9473.982698
HSA-MIR-6835-3P99.9370.492904
HSA-MIR-6809-3P99.9171.453814
HSA-MIR-548E-5P99.8972.734486
HSA-MIR-576-5P99.8470.462582
HSA-MIR-132399.8369.892471
HSA-MIR-548AZ-5P99.8369.943230
HSA-MIR-548T-5P99.8369.913220
HSA-MIR-94499.8270.853042
HSA-MIR-5002-5P99.7670.841763
HSA-MIR-548O-3P99.7469.302228
HSA-MIR-442899.7366.411733
HSA-MIR-488-3P99.6168.791731

Literature-anchored findings (GeneRIF, showing 1)

  • We conclude that coding variants within NFXL1 confer an increased risk of Specific Language Impairment within a complex genetic model (PMID:25781923)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerionfxl1ENSDARG00000070127
mus_musculusNfxl1ENSMUSG00000072889
rattus_norvegicusNfxl1ENSRNOG00000058588
drosophila_melanogasterCG15011FBGN0035518

Paralogs (1): NFX1 (ENSG00000086102)

Protein

Protein identifiers

NF-X1-type zinc finger protein NFXL1Q6ZNB6 (reviewed: Q6ZNB6)

Alternative names: Ovarian zinc finger protein

All UniProt accessions (1): Q6ZNB6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the NFX1 family.

Isoforms (2)

UniProt IDNamesCanonical?
Q6ZNB6-11yes
Q6ZNB6-22

RefSeq proteins (3): NP_001265552, NP_001265553, NP_694540 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000967Znf_NFX1Domain
IPR001841Znf_RINGDomain
IPR034078NFX1_famFamily

Pfam: PF01422

UniProt features (26 total): zinc finger region 11, modified residue 6, splice variant 2, chain 1, transmembrane region 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6ZNB6-F174.400.07

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): 50, 65, 106, 107, 108, 109

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 120 (showing top): RRAGTTGT_UNKNOWN, GCAAGGA_MIR502, chr4p12, FOSTER_TOLERANT_MACROPHAGE_UP, ATGTCAC_MIR489, ACTWSNACTNY_UNKNOWN, CTGAGCC_MIR24, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, CHICAS_RB1_TARGETS_GROWING, SNACANNNYSYAGA_UNKNOWN, MTOR_UP.V1_DN, STK33_SKM_UP, STK33_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, E2F5_TARGET_GENES

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of DNA-templated transcription2
transcription cis-regulatory region binding2
cellular anatomical structure2
DNA-templated transcription1
regulation of gene expression1
regulation of RNA biosynthetic process1
transcription by RNA polymerase II1
chromatin1
RNA polymerase II transcription regulatory region sequence-specific DNA binding1
DNA-binding transcription factor activity1
regulation of transcription by RNA polymerase II1
transition metal ion binding1
transcription regulator activity1
cation binding1
chromosome1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

1273 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NFXL1ATP2C2O75185690
NFXL1CMIPQ8IY22649
NFXL1DNAAF4Q8WXU2578
NFXL1KIAA0319Q5VV43571
NFXL1DCDC2Q9UHG0563
NFXL1CNTNAP2Q9UHC6561
NFXL1ROBO2Q9HCK4508
NFXL1SLAIN2Q9P270496
NFXL1CNGA1P29973494
NFXL1OCIAD1Q9NX40471
NFXL1ROBO1Q9Y6N7459
NFXL1NIPAL1Q6NVV3447
NFXL1SLC10A4Q96EP9433
NFXL1LRRC66Q68CR7418
NFXL1ZNF451Q9Y4E5416

IntAct

93 interactions, top by confidence:

ABTypeScore
TUBA1CTXNDC9psi-mi:“MI:0914”(association)0.730
KLK5DENND11psi-mi:“MI:0914”(association)0.640
SLC1A1AGPAT2psi-mi:“MI:0914”(association)0.640
EGFRNDUFA4psi-mi:“MI:0914”(association)0.530
RPN1APBB1psi-mi:“MI:0914”(association)0.530
TUBB3POTEFpsi-mi:“MI:0914”(association)0.530
TUBA4APLD2psi-mi:“MI:0914”(association)0.530
NCEH1CLGNpsi-mi:“MI:0914”(association)0.530
GALNSCLGNpsi-mi:“MI:0914”(association)0.530
TUBA1ATUBAL3psi-mi:“MI:0914”(association)0.420
NFXL1TOMM20psi-mi:“MI:0915”(physical association)0.400
NFXL1TPRpsi-mi:“MI:0915”(physical association)0.400
FOXL1IFRD1psi-mi:“MI:0914”(association)0.350
RIPK4VWA8psi-mi:“MI:0914”(association)0.350
HSCBRBP5psi-mi:“MI:0914”(association)0.350
SLC16A11ESYT2psi-mi:“MI:0914”(association)0.350
NTRK1ILVBLpsi-mi:“MI:0914”(association)0.350
NTRK3ILVBLpsi-mi:“MI:0914”(association)0.350
GRHL1POLRMTpsi-mi:“MI:0914”(association)0.350
CANXHLA-Apsi-mi:“MI:0914”(association)0.350
DDOSTATL3psi-mi:“MI:0914”(association)0.350
CCDC47ESYT2psi-mi:“MI:0914”(association)0.350
OST4ATL3psi-mi:“MI:0914”(association)0.350
RPN2APBB1psi-mi:“MI:0914”(association)0.350
MGARPBTAF1psi-mi:“MI:0914”(association)0.350
GLMPRTL8Cpsi-mi:“MI:0914”(association)0.350
FFAR1SLC12A8psi-mi:“MI:0914”(association)0.350
GPR182SLC12A8psi-mi:“MI:0914”(association)0.350
RCCD1IFT56psi-mi:“MI:0914”(association)0.350

BioGRID (152): NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Reconstituted Complex), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Proximity Label-MS), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-RNA), NFXL1 (Affinity Capture-MS), NFXL1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMY5, A2YEZ6, A3BDI8, A6QLA0, A9YUB1, B1AY10, D4A4T9, E0X9N4, O74853, P40798, P47226, P53971, Q09YN8, Q0D5B9, Q108U9, Q12986, Q15326, Q17QE2, Q18034, Q29RL2, Q2IBC3, Q2LAP6, Q2QLA1, Q2QLG8, Q4R7U2, Q54BK0, Q5PXT2, Q5R966, Q5RD91, Q5U2P3, Q5ZA07, Q5ZML4, Q67YE6, Q6DIR5, Q6IDS6, Q6NUA0, Q6ZNB6, Q7ZXE9, Q8N6M9, Q8R5C8

Diamond homologs: A0JMY5, A6QLA0, B1AY10, Q12986, Q18034, Q6ZNB6, Q9FFK8, Q9P2E3, Q9SY59, O74853, P40798, Q54BK0, P53971

SIGNOR signaling

1 interactions.

AEffectBMechanism
Ub:E2“up-regulates activity”NFXL1ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 140 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane847.8×5e-10
Transport of connexons to the plasma membrane847.8×5e-10
Gap junction trafficking and regulation841.8×8e-10
Gap junction trafficking841.8×8e-10
Post-chaperonin tubulin folding pathway841.8×8e-10
Metal ion SLC transporters639.6×1e-07
Formation of tubulin folding intermediates by CCT/TriC837.2×2e-09
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding835.9×2e-09

GO biological processes:

GO termPartnersFoldFDR
zinc ion transmembrane transport633.7×1e-05
intracellular zinc ion homeostasis519.3×7e-04
protein N-linked glycosylation612.6×8e-04
microtubule cytoskeleton organization109.7×3e-05
mitotic cell cycle88.6×7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance61
Likely benign2
Benign4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3243 predictions. Top by Δscore:

VariantEffectΔscore
4:47848333:CAGC:Cacceptor_gain1.0000
4:47848335:GCC:Gacceptor_loss1.0000
4:47848337:C:CCacceptor_gain1.0000
4:47848338:T:Cacceptor_loss1.0000
4:47851090:GTTA:Gdonor_loss1.0000
4:47851091:TTA:Tdonor_loss1.0000
4:47851092:TA:Tdonor_loss1.0000
4:47851093:A:Cdonor_loss1.0000
4:47851094:C:CTdonor_loss1.0000
4:47851144:TTTAT:Tacceptor_gain1.0000
4:47851145:TTAT:Tacceptor_gain1.0000
4:47851147:ATCTG:Aacceptor_loss1.0000
4:47851149:C:CCacceptor_gain1.0000
4:47851149:CT:Cacceptor_loss1.0000
4:47851153:T:Cacceptor_gain1.0000
4:47851153:T:TCacceptor_gain1.0000
4:47851155:A:ACacceptor_gain1.0000
4:47851155:A:Cacceptor_gain1.0000
4:47851158:CACA:Cacceptor_gain1.0000
4:47851160:C:CTacceptor_gain1.0000
4:47851161:A:Cacceptor_gain1.0000
4:47855161:AAGC:Aacceptor_loss1.0000
4:47855162:AGC:Aacceptor_loss1.0000
4:47855163:GC:Gacceptor_loss1.0000
4:47855164:C:CAacceptor_loss1.0000
4:47862911:TTTTT:Tacceptor_gain1.0000
4:47862912:TTTT:Tacceptor_gain1.0000
4:47862913:TTT:Tacceptor_gain1.0000
4:47862914:TT:Tacceptor_gain1.0000
4:47862916:C:CCacceptor_gain1.0000

AlphaMissense

5990 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:47890634:A:GC508R1.000
4:47903267:C:AW191C1.000
4:47903267:C:GW191C1.000
4:47903269:A:GW191R1.000
4:47903269:A:TW191R1.000
4:47885927:C:GC539S0.999
4:47885928:A:GC539R0.999
4:47885928:A:TC539S0.999
4:47885985:A:GC520R0.999
4:47885994:A:GC517R0.999
4:47890619:G:CH513D0.999
4:47890621:C:GC512S0.999
4:47890622:A:GC512R0.999
4:47890622:A:TC512S0.999
4:47890632:A:CC508W0.999
4:47890633:C:GC508S0.999
4:47890634:A:TC508S0.999
4:47890638:A:CH506Q0.999
4:47890638:A:TH506Q0.999
4:47890648:C:GC503S0.999
4:47890649:A:GC503R0.999
4:47890649:A:TC503S0.999
4:47890667:A:GC497R0.999
4:47890679:A:GC493R0.999
4:47894191:A:GC481R0.999
4:47894206:A:GC476R0.999
4:47894224:A:GC470R0.999
4:47894236:A:GC466R0.999
4:47899376:G:CH274D0.999
4:47899379:A:GC273R0.999

dbSNP variants (sampled 300 via entrez): RS1000055505 (4:47901700 TA>T), RS1000071439 (4:47878840 T>C), RS1000088810 (4:47866792 T>C), RS1000130155 (4:47914757 G>C,T), RS1000242218 (4:47850611 C>A,T), RS1000290311 (4:47865014 C>A,T), RS1000316337 (4:47851005 C>A,T), RS1000341516 (4:47907607 A>G), RS1000345265 (4:47851674 G>C), RS1000347890 (4:47907995 G>A,C,T), RS1000377198 (4:47900608 G>A,C), RS1000436478 (4:47873766 T>C), RS1000447646 (4:47852046 T>C), RS1000489743 (4:47904949 G>A), RS1000500021 (4:47879314 G>A,T)

Disease associations

OMIM: gene MIM:620488 | 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: yes

ChEMBL targets (1): CHEMBL6067386 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
5.50Kd3185nMCHEMBL5653589
5.50ED503185nMCHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148866: Binding affinity to human NFXL1 incubated for 45 mins by Kinobead based pull down assaykd3.1851uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Cyclosporinedecreases methylation, increases expression, affects cotreatment5
Valproic Aciddecreases expression, increases expression, affects expression3
Air Pollutantsdecreases expression, increases abundance, increases expression2
Estradiolincreases expression2
Tunicamycinincreases expression2
Particulate Matterdecreases expression, increases abundance, increases expression2
FR900359increases phosphorylation1
triphenyl phosphateaffects expression1
propionaldehydeincreases methylation1
pirinixic acidincreases expression, affects binding, increases activity1
bisphenol Adecreases expression1
nonanalincreases methylation1
titanium dioxideincreases methylation1
n-hexanalincreases methylation1
sodium arsenitedecreases expression1
butyraldehydeincreases methylation1
perfluorooctanoic acidincreases expression1
coumarindecreases phosphorylation1
caprylic aldehydeincreases methylation1
pentanalincreases methylation1
heptanalincreases methylation1
nefazodoneaffects cotreatment, increases expression1
di-n-butylphosphoric acidaffects expression1
perfluorooctane sulfonic acidincreases expression1
pentabromodiphenyl etherincreases expression1
jinfukangaffects cotreatment, decreases expression1
Atazanavir Sulfateaffects cotreatment, increases expression1
Resveratrolaffects cotreatment, increases expression1
Sunitinibincreases expression1
Carbamazepineaffects expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5651908BindingBinding affinity to human NFXL1 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.