LUZP4

Summary

LUZP4 (leucine zipper protein 4, HGNC:24971) is a protein-coding gene on chromosome Xq23, encoding Leucine zipper protein 4 (Q9P127). Export adapter involved in mRNA nuclear export in cancer cells.

This gene encodes a leucine-zipper protein that was first defined as a cancer testis antigens. The encoded protein is an RNA binding protein that interacts with the mRNA export receptor nuclear RNA export factor 2. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 51213 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_016383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24971
Approved symbol	LUZP4
Name	leucine zipper protein 4
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	HOM-TES-85, CT-8, CT28
Ensembl gene	ENSG00000102021
Ensembl biotype	protein_coding
OMIM	300616
Entrez	51213

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000371920, ENST00000371921

RefSeq mRNA: 2 — MANE Select: NM_016383 NM_001318840, NM_016383

CCDS: CCDS14567

Canonical transcript exons

ENST00000371920 — 4 exons

Exon	Start	End
ENSE00000675048	115303300	115303418
ENSE00001901510	115306205	115307563
ENSE00001951050	115289715	115289850
ENSE00003680383	115301992	115302123

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 96.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1007 / max 66.7691, expressed in 9 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197322	0.0937	8
197321	0.0070	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.66	gold quality
olfactory bulb	UBERON:0002264	70.52	gold quality
type B pancreatic cell	CL:0000169	70.35	gold quality
testis	UBERON:0000473	67.58	gold quality
right testis	UBERON:0004534	67.24	gold quality
left testis	UBERON:0004533	66.17	gold quality
epithelium of nasopharynx	UBERON:0001951	62.42	gold quality
tibialis anterior	UBERON:0001385	61.83	silver quality
mucosa of paranasal sinus	UBERON:0005030	61.05	gold quality
diaphragm	UBERON:0001103	60.79	gold quality
mucosa of urinary bladder	UBERON:0001259	60.55	gold quality
germinal epithelium of ovary	UBERON:0001304	58.78	gold quality
superficial temporal artery	UBERON:0001614	57.30	gold quality
ileal mucosa	UBERON:0000331	56.74	silver quality
quadriceps femoris	UBERON:0001377	54.29	gold quality
deltoid	UBERON:0001476	53.82	gold quality
thymus	UBERON:0002370	53.52	gold quality
cervix epithelium	UBERON:0004801	53.51	gold quality
vastus lateralis	UBERON:0001379	53.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	52.63	gold quality
kidney epithelium	UBERON:0004819	52.62	gold quality
epithelial cell of pancreas	CL:0000083	51.53	gold quality
oviduct epithelium	UBERON:0004804	50.94	gold quality
nasal cavity epithelium	UBERON:0005384	49.94	gold quality
CA1 field of hippocampus	UBERON:0003881	49.92	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.78	gold quality
myocardium	UBERON:0002349	49.43	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting LUZP4, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-581	98.39	67.42	835
HSA-MIR-10395-3P	98.10	66.70	1726

Literature-anchored findings (GeneRIF, showing 2)

• A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing. (PMID:12032826)
• Luzp4 is an RNA-binding protein which associates with the TREX mRNA export complex subunit Uap56. Luzp4 also binds the principal mRNA export receptor Nxf1, enhances its RNA binding activity and complements Alyref knockdown in vivo. Luzp4 displays all features of an mRNA export adaptor. Whilst Luzp4 is up-regulated in a range of tumours, it appears preferentially expressed in melanoma cells where it is required for growth. (PMID:25662211)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Leucine zipper protein 4 — Q9P127 (reviewed: Q9P127)

Alternative names: Cancer/testis antigen 28, Tumor antigen HOM-TES-85

All UniProt accessions (2): Q9P127, Q5JX98

UniProt curated annotations — full annotation on UniProt →

Function. Export adapter involved in mRNA nuclear export in cancer cells. Binds and enhances the RNA-binding activity of the nuclear RNA export factor NXF1. Can restore mRNA export function in cells compromised by loss of mRNA export adapters.

Subunit / interactions. Interacts with NXF1, NXF2, THOC1, THOC5, DDX39B/UAP56 and SRRT.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed specifically in testis. Also expressed in a wide variety of cancer types, but particularly high levels of expression observed in melanoma cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P127-1	1	yes
Q9P127-2	2

RefSeq proteins (2): NP_001305769, NP_057467* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR050768	UPF0353/GerABKA_families	Family

UniProt features (22 total): compositionally biased region 8, region of interest 7, splice variant 2, sequence variant 2, chain 1, modified residue 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P127-F1	66.63	0.31

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 (1): 234

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 56 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_NUCLEAR_TRANSPORT, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_NUCLEAR_EXPORT, GOBP_RNA_LOCALIZATION, REACTOME_METABOLISM_OF_RNA, GOCC_TRANSCRIPTION_EXPORT_COMPLEX, XU_GH1_EXOGENOUS_TARGETS_DN, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, chrXq23, GOBP_RNA_EXPORT_FROM_NUCLEUS, GOBP_MRNA_EXPORT_FROM_NUCLEUS

GO Biological Process (1): mRNA transport (GO:0051028)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	2
Transport of Mature Transcript to Cytoplasm	1
RNA Polymerase II Transcription	1
Metabolism of RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA transport	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LUZP4	SRSF2	Q01130	762
LUZP4	NXF1	Q9UBU9	716
LUZP4	DDX39B	Q13838	623
LUZP4	NXT1	Q9UKK6	600
LUZP4	KLHL11	Q9NVR0	581
LUZP4	SSX1	Q16384	576
LUZP4	SSX4	O60224	575
LUZP4	SPACA3	Q8IXA5	552
LUZP4	FYTTD1	Q96QD9	541
LUZP4	MAGEC1	O60732	541
LUZP4	LRRFIP2	Q9Y608	479
LUZP4	PNLDC1	Q8NA58	478
LUZP4	RBM47	A0AV96	447
LUZP4	CTAG1A	P78358	447
LUZP4	CHTOP	Q9Y3Y2	447

IntAct

76 interactions, top by confidence:

A	B	Type	Score
LUZP4	EMD	psi-mi:“MI:0915”(physical association)	0.810
EMD	LUZP4	psi-mi:“MI:0915”(physical association)	0.810
CLK2	LUZP4	psi-mi:“MI:0915”(physical association)	0.720
APPBP2	LUZP4	psi-mi:“MI:0915”(physical association)	0.720
LUZP4	CLK2	psi-mi:“MI:0915”(physical association)	0.720
LUZP4	APPBP2	psi-mi:“MI:0915”(physical association)	0.720
FOSL2	LUZP4	psi-mi:“MI:0915”(physical association)	0.560
LUZP4	SRPK2	psi-mi:“MI:0915”(physical association)	0.560
	LUZP4	psi-mi:“MI:0915”(physical association)	0.560
LUZP4	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.560
LUZP4	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
LUZP4	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
LUZP4	FOS	psi-mi:“MI:0915”(physical association)	0.560
RCOR3	LUZP4	psi-mi:“MI:0915”(physical association)	0.560
LUZP4	TLK1	psi-mi:“MI:0915”(physical association)	0.560
LUZP4	FOSL2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	LUZP4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (109): LUZP4 (Two-hybrid), LUZP4 (Two-hybrid), LUZP4 (Two-hybrid), LUZP4 (Two-hybrid), LUZP4 (Two-hybrid), LUZP4 (Two-hybrid), LUZP4 (Two-hybrid), RCOR3 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), ACTN4 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), PPP1R12A (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUY1, A6NJ88, A6QL64, B3KS81, E9Q6E9, O43493, O48582, O77733, P04279, P0C7A4, P0C7A5, P0CV57, P0DKJ7, P10322, P16225, P48997, P48998, Q02383, Q06990, Q08AG5, Q0ZNK1, Q5JPF3, Q5JRC9, Q5SRN2, Q5U7M7, Q5U7M8, Q5U7M9, Q5U7N0, Q5U7N1, Q5U7N3, Q5U7N4, Q5XHX6, Q659K0, Q6AYN3, Q6JHY2, Q6P902, Q6SJ82, Q6X2M3, Q6XPR3, Q80Y39

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	15
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

682 predictions. Top by Δscore:

Variant	Effect	Δscore
X:115301985:A:AG	acceptor_gain	1.0000
X:115301986:A:G	acceptor_gain	0.9900
X:115301987:TACAG:T	acceptor_loss	0.9900
X:115301989:CA:C	acceptor_loss	0.9900
X:115301990:A:AG	acceptor_gain	0.9900
X:115301990:A:C	acceptor_loss	0.9900
X:115301991:G:GA	acceptor_gain	0.9900
X:115301991:GAC:G	acceptor_gain	0.9900
X:115302121:GAG:G	donor_gain	0.9900
X:115302122:AG:A	donor_loss	0.9900
X:115302123:GGTAA:G	donor_loss	0.9900
X:115302125:T:C	donor_loss	0.9900
X:115302129:G:GG	donor_gain	0.9900
X:115303423:A:G	donor_gain	0.9900
X:115306187:AATTG:A	acceptor_gain	0.9900
X:115301975:T:G	acceptor_gain	0.9800
X:115301990:AGAC:A	acceptor_gain	0.9800
X:115301991:GA:G	acceptor_gain	0.9800
X:115301991:GACG:G	acceptor_gain	0.9800
X:115301991:GACGA:G	acceptor_gain	0.9800
X:115303296:AAAG:A	acceptor_gain	0.9800
X:115306187:A:AG	acceptor_gain	0.9800
X:115306187:AATT:A	acceptor_gain	0.9800
X:115289826:GT:G	donor_gain	0.9700
X:115289827:TT:T	donor_gain	0.9700
X:115289839:A:G	donor_gain	0.9700
X:115289847:CTAGG:C	donor_loss	0.9700
X:115289851:G:T	donor_loss	0.9700
X:115289852:T:A	donor_loss	0.9700
X:115301989:C:G	acceptor_gain	0.9700

AlphaMissense

2050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:115289832:T:C	F25L	0.850
X:115289834:C:A	F25L	0.850
X:115289834:C:G	F25L	0.850
X:115306638:T:C	L259P	0.831
X:115306617:T:C	L252P	0.791
X:115306659:T:C	L266P	0.782
X:115306680:T:C	L273P	0.711
X:115306630:G:C	Q256H	0.697
X:115306630:G:T	Q256H	0.697
X:115302010:A:T	K37I	0.692
X:115302011:A:C	K37N	0.666
X:115302011:A:T	K37N	0.666
X:115306651:G:C	Q263H	0.650
X:115306651:G:T	Q263H	0.650
X:115289843:G:A	M28I	0.648
X:115289843:G:C	M28I	0.648
X:115289843:G:T	M28I	0.648
X:115306629:A:C	Q256P	0.638
X:115306664:G:C	A268P	0.632
X:115301998:T:G	I33S	0.631
X:115306596:T:C	L245P	0.629
X:115306672:G:C	Q270H	0.619
X:115306672:G:T	Q270H	0.619
X:115306622:G:C	A254P	0.618
X:115306650:A:C	Q263P	0.607
X:115301995:A:T	D32V	0.601
X:115306643:G:C	A261P	0.600
X:115306609:G:C	Q249H	0.592
X:115306609:G:T	Q249H	0.592
X:115306671:A:C	Q270P	0.581

dbSNP variants (sampled 300 via entrez): RS1000072216 (X:115301248 A>G), RS1000222638 (X:115293354 C>A), RS1001305878 (X:115302845 A>G), RS1001380762 (X:115302343 G>T), RS1001412917 (X:115293749 G>A), RS1001481098 (X:115299763 A>G,T), RS1001989861 (X:115293940 G>C), RS1002426496 (X:115300788 C>A), RS1002809962 (X:115292040 C>T), RS1002832532 (X:115304278 C>G,T), RS1003049776 (X:115304827 A>G), RS1003242092 (X:115288523 G>A,T), RS1003261514 (X:115296195 A>G), RS1003492647 (X:115295428 A>T), RS1004204770 (X:115306147 T>C)

Disease associations

OMIM: gene MIM:300616 | 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Aflatoxin B1	affects expression	1

Clinical trials (associated diseases)

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