SPZ1

Summary

SPZ1 (spermatogenic leucine zipper 1, HGNC:30721) is a protein-coding gene on chromosome 5q14.1, encoding Spermatogenic leucine zipper protein 1 (Q9BXG8). Transcription factor that binds to the DNA sequence 5’-CANNTG-3’(E box) and the G-box motif.

This gene encodes a bHLH-zip transcription factor which functions in the mitogen-activate protein kinase (MAPK) signaling pathway. Because of its role in the upregulation of cell proliferation and tumorigenesis, this gene may serve as a target for Ras-induced tumor treatments.

Source: NCBI Gene 84654 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_032567

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30721
Approved symbol	SPZ1
Name	spermatogenic leucine zipper 1
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	NYD-TSP1, FLJ25709, PPP1R148
Ensembl gene	ENSG00000164299
Ensembl biotype	protein_coding
OMIM	618068
Entrez	84654

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000296739, ENST00000511881

RefSeq mRNA: 1 — MANE Select: NM_032567 NM_032567

CCDS: CCDS43336

Canonical transcript exons

ENST00000296739 — 1 exons

Exon	Start	End
ENSE00001083204	80320002	80321842

Expression profiles

Bgee: expression breadth broad, 21 present calls, max score 98.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0135 / max 11.7036, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57299	0.0135	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	98.19	gold quality
left testis	UBERON:0004533	87.72	gold quality
right testis	UBERON:0004534	87.60	gold quality
testis	UBERON:0000473	85.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.47	gold quality
adult organism	UBERON:0007023	55.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.03	gold quality
buccal mucosa cell	CL:0002336	51.05	gold quality
myocardium	UBERON:0002349	50.25	gold quality
tibialis anterior	UBERON:0001385	47.99	silver quality
cauda epididymis	UBERON:0004360	47.45	silver quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
deltoid	UBERON:0001476	46.69	gold quality
pancreatic ductal cell	CL:0002079	46.63	silver quality
quadriceps femoris	UBERON:0001377	46.51	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
ileal mucosa	UBERON:0000331	45.37	silver quality
lower lobe of lung	UBERON:0008949	44.63	silver quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
muscle tissue	UBERON:0002385	40.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CCN2
PCNA	Activation
TPM1

miRNA regulators (miRDB)

28 targeting SPZ1, 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-524-5P	99.98	73.43	4882
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-626	98.89	66.21	762
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-7852-3P	98.37	67.98	823
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-630	97.50	66.38	921
HSA-MIR-4535	97.27	65.17	469
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-7161-3P	96.79	68.79	798
HSA-MIR-659-5P	95.36	65.00	300
HSA-MIR-4513	95.04	67.06	727
HSA-MIR-6855-3P	95.04	66.57	725

Literature-anchored findings (GeneRIF, showing 6)

• highly expressed in adult testis; may play an important role in spermatogenesis in the humans (PMID:12778315)
• SPZ1 promotes epithelial-mesenchymal transition (EMT) by trans-activating the gene of TWIST1. A clinical analysis showed a marker association of SPZ1 and TWIST1 with induction of tumorigenesis in HCC patients. (PMID:28368406)
• Tip60 mediates acetylation at lysine residues of SPZ1 at positions 369 and 374 which are required for SPZ1-TWIST1 complex formation and cancer cell migration in vitro and in vivo. (PMID:30154425)
• SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer. (PMID:31934723)
• TSP1 is the essential domain of SEMA5A involved in pannus formation in rheumatoid arthritis. (PMID:33616619)
• SPZ1 promotes glioma aggravation via targeting CXXC4. (PMID:34076982)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spz1	ENSMUSG00000046957
rattus_norvegicus	Spz1	ENSRNOG00000013050
drosophila_melanogaster	Tango1	FBGN0286898

Paralogs (10): OTOR (ENSG00000125879), MIA2 (ENSG00000150527), MIA3 (ENSG00000154305), CTAGE1 (ENSG00000212710), CTAGE9 (ENSG00000236761), MIA (ENSG00000261857), CTAGE15 (ENSG00000271079), CTAGE6 (ENSG00000271321), CTAGE4 (ENSG00000288784), CTAGE8 (ENSG00000289604)

Protein

Protein identifiers

Spermatogenic leucine zipper protein 1 — Q9BXG8 (reviewed: Q9BXG8)

Alternative names: Testis-specific protein 1, Testis-specific protein NYD-TSP1

All UniProt accessions (3): A0A140VKA5, D6RFL8, Q9BXG8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds to the DNA sequence 5’-CANNTG-3’(E box) and the G-box motif. May play an important role in the regulation of cell proliferation and differentiation during spermatogenesis.

Subunit / interactions. Interacts with PPP1CC isoform gamma-2.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Specifically and strongly expressed in the testis. Expressed in several tumor cell lines.

Post-translational modifications. Phosphorylated by MAPK1/ERK2 and MAPK3/ERK1.

Miscellaneous. The helix-loop-helix and basic motifs form a SPZ1 specific bHLH different from the classical one.

RefSeq proteins (1): NP_115956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR042961	Spz1	Family

UniProt features (15 total): region of interest 4, sequence conflict 3, coiled-coil region 3, sequence variant 2, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXG8-F1	68.04	0.18

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 (2): 107, 258

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, MODULE_95, BOCHKIS_FOXA2_TARGETS, MODULE_49, MODULE_163, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GSE10239_KLRG1INT_VS_KLRG1HIGH_EFF_CD8_TCELL_UP, MIR93_3P, MIR508_3P, MIR4464, MIR4748, MIR4513, MIR6855_3P, SYATTGTG_UNKNOWN, GSE17721_POLYIC_VS_GARDIQUIMOD_24H_BMDC_UP

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1105 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPZ1	PAX4	O43316	615
SPZ1	TWIST1	Q15672	535
SPZ1	CRISP2	P16562	463
SPZ1	TCP11	Q8WWU5	390
SPZ1	MEA1	Q16626	389
SPZ1	SPATA4	Q8NEY3	384
SPZ1	PLAAT5	Q96KN8	374
SPZ1	KLHDC3	Q9BQ90	374
SPZ1	SCP2D1	Q9UJQ7	352
SPZ1	NHLH1	Q02575	342
SPZ1	HIC1	Q14526	334
SPZ1	PHF7	Q9BWX1	326
SPZ1	ZSCAN4	Q8NAM6	320
SPZ1	ZMYND10	O75800	318
SPZ1	CREM	Q03060	313

IntAct

16 interactions, top by confidence:

A	B	Type	Score
DTNB	SPZ1	psi-mi:“MI:0915”(physical association)	0.670
SPZ1	DTNB	psi-mi:“MI:0915”(physical association)	0.670
HERC2	SPZ1	psi-mi:“MI:0915”(physical association)	0.670
DTNB	SPZ1	psi-mi:“MI:0915”(physical association)	0.560
SPZ1	GAPDHS	psi-mi:“MI:0914”(association)	0.530
HOXB9	SPZ1	psi-mi:“MI:0915”(physical association)	0.370
SPZ1	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
SPZ1	OFD1	psi-mi:“MI:0914”(association)	0.350
DTNB	SPZ1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): SPZ1 (Two-hybrid), HERC2 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), DTNA (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), SNTB2 (Affinity Capture-MS), SNTA1 (Affinity Capture-MS), SPZ1 (Reconstituted Complex), NEURL4 (Affinity Capture-MS), HERC2 (Affinity Capture-MS), DTNA (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), SNTA1 (Affinity Capture-MS), SNTB2 (Affinity Capture-MS), SPZ1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GVN3, A4FU49, A6NHN6, A6NI47, A6NJ64, A6QQS3, A7KBS4, E9PQR5, O75200, O75459, O96001, P0C2X8, P0C7A2, P22575, P88825, Q13127, Q28181, Q2HR71, Q32MG2, Q4R729, Q4R8H9, Q4V8E9, Q5JRC9, Q5R7U0, Q5SRN2, Q63HK3, Q6AXV6, Q6IC83, Q6PGQ1, Q6S545, Q6S5H5, Q6SJ82, Q70KF4, Q7Z2Y5, Q80VJ6, Q80YD3, Q8IZU0, Q8N660, Q8NA70, Q923B3

Diamond homologs: Q32L17, Q6AXY9, Q99MY0, Q9BXG8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	9
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

91 predictions. Top by Δscore:

Variant	Effect	Δscore
5:80320972:G:GT	donor_gain	0.5200
5:80320985:G:GT	donor_gain	0.5000
5:80321047:A:G	donor_gain	0.4600
5:80321255:G:T	donor_gain	0.4600
5:80321101:G:GT	donor_gain	0.4400
5:80321044:GACA:G	donor_gain	0.4300
5:80321641:G:GT	donor_gain	0.4100
5:80321254:GGAAC:G	donor_gain	0.4000
5:80321004:GCTCA:G	donor_gain	0.3900
5:80321110:GC:G	donor_gain	0.3900
5:80321008:A:AG	donor_gain	0.3700
5:80321009:G:GG	donor_gain	0.3700
5:80321047:A:AG	donor_gain	0.3700
5:80321111:C:G	donor_gain	0.3700
5:80321005:C:G	donor_gain	0.3600
5:80321168:A:AG	acceptor_gain	0.3300
5:80321169:G:GG	acceptor_gain	0.3300
5:80320672:G:GT	donor_gain	0.3200
5:80320988:G:GG	donor_gain	0.3200
5:80320987:A:AG	donor_gain	0.3100
5:80320703:G:GT	donor_gain	0.3000
5:80320841:A:G	donor_gain	0.3000
5:80321169:GTT:G	acceptor_gain	0.3000
5:80321233:G:GT	donor_gain	0.3000
5:80321281:A:G	donor_gain	0.2900
5:80321642:A:T	donor_gain	0.2900
5:80321328:GAAA:G	donor_gain	0.2800
5:80321367:GG:G	donor_gain	0.2800
5:80321368:GG:G	donor_gain	0.2800
5:80321629:C:G	donor_gain	0.2700

AlphaMissense

2902 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:80320975:G:C	A254P	0.960
5:80321006:T:C	L264P	0.934
5:80321015:T:C	L267P	0.919
5:80321176:G:C	A321P	0.893
5:80321179:G:C	A322P	0.891
5:80320967:T:C	L251P	0.882
5:80321144:T:C	L310P	0.882
5:80321186:T:C	L324P	0.882
5:80320984:T:A	W257R	0.881
5:80320984:T:C	W257R	0.881
5:80320964:T:C	L250S	0.857
5:80320986:G:C	W257C	0.856
5:80320986:G:T	W257C	0.856
5:80320430:T:C	L72P	0.827
5:80320956:G:A	M247I	0.806
5:80320956:G:C	M247I	0.806
5:80320956:G:T	M247I	0.806
5:80321228:T:C	L338P	0.803
5:80321424:G:C	K403N	0.801
5:80321424:G:T	K403N	0.801
5:80320454:T:C	L80P	0.789
5:80321217:A:C	R334S	0.776
5:80321217:A:T	R334S	0.776
5:80321207:T:C	L331S	0.772
5:80320831:T:C	F206L	0.756
5:80320833:T:A	F206L	0.756
5:80320833:T:G	F206L	0.756
5:80320997:A:C	H261P	0.756
5:80321443:T:C	F410L	0.756
5:80321445:C:A	F410L	0.756

dbSNP variants (sampled 300 via entrez): RS1001711896 (5:80318851 C>T), RS1002556609 (5:80319564 G>A), RS1003458873 (5:80320808 A>C,G,T), RS1004436420 (5:80321052 T>A), RS1005437095 (5:80319213 C>T), RS1006375893 (5:80318035 G>T), RS10069319 (5:80322228 T>A,C,G), RS1007104375 (5:80318817 A>G), RS1007935402 (5:80321948 G>A), RS1007966600 (5:80321572 T>A), RS1009106719 (5:80322143 G>C), RS1009928855 (5:80318489 G>A,T), RS1010000969 (5:80318176 A>G), RS1010619073 (5:80318288 G>A), RS1011206247 (5:80319874 A>C,G)

Disease associations

OMIM: gene MIM:618068 | 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
Decitabine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	decreases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6R2	SEES3-1V human SPZ1, clone1	Embryonic stem cell	Male
CVCL_A6R3	SEES3-1V human SPZ1, clone2	Embryonic stem cell	Male
CVCL_A6R4	SEES3-1V human SPZ1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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