STPG4

Summary

STPG4 (sperm-tail PG-rich repeat containing 4, HGNC:26850) is a protein-coding gene on chromosome 2p21, encoding Protein STPG4 (Q8N801). Maternal factor that plays a role in epigenetic chromatin reprogramming during early development of the zygote.

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in epigenetic programing of male pronucleus. Predicted to act upstream of or within pyrimidine-containing compound catabolic process. Predicted to be located in cytoplasm and nucleus. Predicted to be active in female pronucleus; germinal vesicle; and male pronucleus.

Source: NCBI Gene 285051 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001163561

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26850
Approved symbol	STPG4
Name	sperm-tail PG-rich repeat containing 4
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40172
Ensembl gene	ENSG00000239605
Ensembl biotype	protein_coding
Entrez	285051

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000294947, ENST00000445927, ENST00000449846, ENST00000464527, ENST00000482548, ENST00000496939

RefSeq mRNA: 2 — MANE Select: NM_001163561 NM_001163561, NM_173649

CCDS: CCDS1831, CCDS54356

Canonical transcript exons

ENST00000445927 — 7 exons

Exon	Start	End
ENSE00001736202	47155171	47155308
ENSE00003891050	47129941	47129995
ENSE00003891234	47152957	47153016
ENSE00003891447	47130196	47130260
ENSE00003893767	47090270	47090374
ENSE00003894140	47086991	47087130
ENSE00003894828	47151258	47151515

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 81.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1076 / max 34.7335, expressed in 33 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28211	0.0375	18
28210	0.0308	16
28212	0.0303	3
28213	0.0090	3

Top tissues by expression

134 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	81.47	gold quality
left testis	UBERON:0004533	80.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.00	gold quality
testis	UBERON:0000473	79.88	gold quality
right testis	UBERON:0004534	79.04	gold quality
monocyte	CL:0000576	63.65	gold quality
leukocyte	CL:0000738	62.98	gold quality
granulocyte	CL:0000094	62.96	gold quality
blood	UBERON:0000178	57.61	gold quality
vagina	UBERON:0000996	57.61	gold quality
smooth muscle tissue	UBERON:0001135	56.78	gold quality
ectocervix	UBERON:0012249	55.59	gold quality
skin of leg	UBERON:0001511	55.34	gold quality
endocervix	UBERON:0000458	54.97	gold quality
zone of skin	UBERON:0000014	54.78	gold quality
uterine cervix	UBERON:0000002	54.67	gold quality
corpus callosum	UBERON:0002336	54.65	gold quality
urinary bladder	UBERON:0001255	54.31	gold quality
skin of abdomen	UBERON:0001416	53.97	gold quality
tonsil	UBERON:0002372	53.38	gold quality
mucosa of stomach	UBERON:0001199	53.16	gold quality
bone marrow	UBERON:0002371	51.87	gold quality
cortical plate	UBERON:0005343	51.34	gold quality
gall bladder	UBERON:0002110	51.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	50.80	gold quality
tibial nerve	UBERON:0001323	50.65	gold quality
spleen	UBERON:0002106	49.36	gold quality
right adrenal gland	UBERON:0001233	49.29	gold quality
sural nerve	UBERON:0015488	49.09	silver quality
bone marrow cell	CL:0002092	48.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting STPG4, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-376B-5P	98.46	66.40	606
HSA-MIR-376C-5P	98.46	66.64	589
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-581	98.39	67.42	835
HSA-MIR-147A	98.33	66.40	795

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Stpg4	ENSMUSG00000036557
rattus_norvegicus	Stpg4	ENSRNOG00000040136

Protein

Protein identifiers

Protein STPG4 — Q8N801 (reviewed: Q8N801)

Alternative names: Gonad-specific expression gene protein, Sperm-tail PG-rich repeat-containing protein 4

All UniProt accessions (2): Q8N801, H7C3W9

UniProt curated annotations — full annotation on UniProt →

Function. Maternal factor that plays a role in epigenetic chromatin reprogramming during early development of the zygote. Involved in the regulation of gametic DNA demethylation by inducing the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC).

Subunit / interactions. Interacts with histone H3. Interacts with histone H4.

Subcellular location. Cytoplasm. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N801-1	1	yes
Q8N801-2	2

RefSeq proteins (2): NP_001157033, NP_775920 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010736	SHIPPO-rpt	Repeat

Pfam: PF07004

UniProt features (4 total): sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N801-F1	67.29	0.01

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9821002	Chromatin modifications during the maternal to zygotic transition (MZT)
R-HSA-1266738	Developmental Biology
R-HSA-9816359	Maternal to zygotic transition (MZT)

MSigDB gene sets: 46 (showing top): GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_CHROMATIN_BINDING, GOCC_GERM_CELL_NUCLEUS, GOCC_PRONUCLEUS, GOMF_HISTONE_BINDING, HEIDENBLAD_AMPLICON_8Q24_UP, GOCC_FEMALE_PRONUCLEUS, GOCC_MALE_PRONUCLEUS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, FEV_TARGET_GENES, FOXD2_TARGET_GENES, LHX9_TARGET_GENES

GO Biological Process (3): epigenetic programing of male pronucleus (GO:0044727), pyrimidine-containing compound catabolic process (GO:0072529), chromatin organization (GO:0006325)

GO Molecular Function (3): chromatin binding (GO:0003682), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (7): male germ cell nucleus (GO:0001673), female pronucleus (GO:0001939), male pronucleus (GO:0001940), nucleus (GO:0005634), cytoplasm (GO:0005737), germinal vesicle (GO:0042585), female germ cell nucleus (GO:0001674)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
germ cell nucleus	2
pronucleus	2
epigenetic programming in the zygotic pronuclei	1
catabolic process	1
pyrimidine-containing compound metabolic process	1
cellular component organization	1
protein binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
female germ cell nucleus	1

Protein interactions and networks

STRING

120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STPG4	TMEM247	A6NEH6	541
STPG4	ANKRD30BL	A7E2S9	528
STPG4	MANBAL	Q9NQG1	506
STPG4	PPP1R21	Q6ZMI0	477
STPG4	CREG2	Q8IUH2	472
STPG4	KCNK12	Q9HB15	472
STPG4	GTF2A1L	Q9UNN4	472
STPG4	STON1	Q9Y6Q2	447
STPG4	Q53S48	Q53S48	445
STPG4	MARCHF10	Q8NA82	430
STPG4	ZBTB5	O15062	419
STPG4	TLCD3A	Q8TBR7	417
STPG4	ENTREP1	Q15884	413
STPG4	SEC31B	Q9NQW1	400
STPG4	NSMCE1	Q8WV22	391

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TLK2	PES1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (4): C2orf61 (Affinity Capture-MS), C2orf61 (Affinity Capture-RNA), C2orf61 (Two-hybrid), C2orf61 (Co-fractionation)

ESM2 similar proteins: A1A5R9, A2AVQ5, A2RRW4, A2RSX4, A5WUY6, A9JS51, B0BM24, B0S4Q5, B1H283, D4A039, F1MMV1, Q08BC4, Q0VB26, Q2T9Q3, Q2TA11, Q2TBS4, Q3KQ80, Q3SX64, Q3TZ65, Q3ZCV2, Q4KKZ1, Q4KLY8, Q4R5Y0, Q5PQN4, Q5RAF2, Q5XI56, Q6ZN84, Q810P2, Q8BUG5, Q8C008, Q8C8J0, Q8IXM7, Q8N412, Q8N6G2, Q8N7U6, Q8N801, Q8TCI5, Q8WW14, Q9D067, Q9D131

Diamond homologs: Q8N801, Q9DAG5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2119 predictions. Top by Δscore:

Variant	Effect	Δscore
2:47046313:A:AG	acceptor_gain	1.0000
2:47046313:AGCCT:A	acceptor_gain	1.0000
2:47046314:G:GA	acceptor_gain	1.0000
2:47046314:GC:G	acceptor_gain	1.0000
2:47046314:GCC:G	acceptor_gain	1.0000
2:47046314:GCCT:G	acceptor_gain	1.0000
2:47046314:GCCTG:G	acceptor_gain	1.0000
2:47046429:GGG:G	donor_gain	1.0000
2:47046430:GG:G	donor_gain	1.0000
2:47046430:GGG:G	donor_gain	1.0000
2:47046430:GGGT:G	donor_loss	1.0000
2:47046431:GG:G	donor_gain	1.0000
2:47046432:G:A	donor_loss	1.0000
2:47046432:G:GG	donor_gain	1.0000
2:47046433:T:G	donor_loss	1.0000
2:47051876:GGCTG:G	donor_gain	1.0000
2:47051877:GCTGG:G	donor_gain	1.0000
2:47060764:T:TA	acceptor_gain	1.0000
2:47060764:TGCA:T	acceptor_loss	1.0000
2:47060765:GCA:G	acceptor_loss	1.0000
2:47060766:CA:C	acceptor_loss	1.0000
2:47060767:A:AG	acceptor_gain	1.0000
2:47060767:A:T	acceptor_loss	1.0000
2:47060767:AGCT:A	acceptor_gain	1.0000
2:47060768:G:GT	acceptor_gain	1.0000
2:47060768:GC:G	acceptor_gain	1.0000
2:47060768:GCT:G	acceptor_gain	1.0000
2:47060768:GCTG:G	acceptor_gain	1.0000
2:47060768:GCTGA:G	acceptor_gain	1.0000
2:47060967:GCCTG:G	donor_gain	1.0000

AlphaMissense

1606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:47090306:A:C	F196L	0.976
2:47090306:A:T	F196L	0.976
2:47090308:A:G	F196L	0.976
2:47151432:A:C	F75L	0.976
2:47151432:A:T	F75L	0.976
2:47151434:A:G	F75L	0.976
2:47151417:C:A	R80S	0.975
2:47151417:C:G	R80S	0.975
2:47129983:A:C	F159L	0.974
2:47129983:A:T	F159L	0.974
2:47129985:A:G	F159L	0.974
2:47152974:A:G	W42R	0.971
2:47152974:A:T	W42R	0.971
2:47151306:G:C	F117L	0.966
2:47151306:G:T	F117L	0.966
2:47151308:A:G	F117L	0.966
2:47151433:A:G	F75S	0.962
2:47152977:A:G	W41R	0.956
2:47152977:A:T	W41R	0.956
2:47090307:A:G	F196S	0.952
2:47151477:A:C	F60L	0.952
2:47151477:A:T	F60L	0.952
2:47151479:A:G	F60L	0.952
2:47129984:A:G	F159S	0.950
2:47152972:C:A	W42C	0.950
2:47152972:C:G	W42C	0.950
2:47151418:C:G	R80T	0.947
2:47151429:T:A	K76N	0.946
2:47151429:T:G	K76N	0.946
2:47129965:T:A	R165S	0.945

dbSNP variants (sampled 300 via entrez): RS1000000482 (2:47087805 T>C,G), RS1000068033 (2:47129037 G>T), RS1000074800 (2:47089294 T>C), RS1000082160 (2:47149482 A>G), RS1000093617 (2:47095877 G>C,T), RS1000124891 (2:47096077 T>C), RS1000199774 (2:47109802 T>C), RS1000208697 (2:47154976 T>C,G), RS1000216965 (2:47143333 A>C), RS1000264552 (2:47091516 A>C), RS1000273684 (2:47087460 G>GC), RS1000331975 (2:47106005 T>C), RS1000428397 (2:47114650 G>A), RS1000440819 (2:47095482 C>G,T), RS1000486179 (2:47123668 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): Lynch syndrome (MONDO:0005835)

Orphanet (1): Lynch syndrome (Orphanet:144)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000635_23	Response to statin therapy	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases methylation	1
benzo(e)pyrene	increases methylation	1
caprylic aldehyde	increases methylation	1
pentanal	increases methylation	1
heptanal	increases methylation	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Catechin	affects cotreatment, increases expression	1
Copper	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00566644	PHASE3	TERMINATED	Intrauterine Levonorgestrel and Observation or Observation Alone in Preventing Atypical Endometrial Hyperplasia and Endometrial Cancer in Women With Hereditary Non-Polyposis Colorectal Cancer or Lynch Syndrome
NCT02000089	PHASE3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT02813824	PHASE3	ACTIVE_NOT_RECRUITING	Effect of Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome
NCT02912559	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair
NCT04711434	PHASE3	UNKNOWN	PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients
NCT07609901	PHASE3	NOT_YET_RECRUITING	Preventive Dendritic Cell Vaccination for Lynch Syndrome Carriers
NCT03631641	PHASE2	TERMINATED	Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy
NCT03831698	PHASE2	UNKNOWN	Omega 3 Fatty Acids in Colorectal Cancer (CRC) Prevention in Patients With Lynch Syndrome (COLYNE)
NCT04920149	PHASE2	RECRUITING	Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome
NCT05411718	PHASE2	RECRUITING	A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome
NCT05419011	PHASE2	ACTIVE_NOT_RECRUITING	Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome
NCT02052908	PHASE1	COMPLETED	Naproxen in Preventing DNA Mismatch Repair Deficient Colorectal Cancer in Patients With Lynch Syndrome
NCT02359565	PHASE1	ACTIVE_NOT_RECRUITING	Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma
NCT04500548	PHASE1	WITHDRAWN	Testing the Combination of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) in Children, Adolescent, and Young Adult Patients With Relapsed/Refractory Cancers That Have an Increased Number of Genetic Changes, The 3CI Study
NCT07163403	PHASE1	RECRUITING	First in Human Pilot Study to Assess the Safety and Efficacy of Dendritic Cells Loaded With Frameshift Derived Neopeptides for the Prevention of Cancer in of Lynch Syndrome Carriers
NCT05078866	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients
NCT07412197	PHASE1/PHASE2	NOT_YET_RECRUITING	Preventive Dendritic Cell Vaccination for Lynch Syndrome
NCT00898768	EARLY_PHASE1	COMPLETED	Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT04379999	EARLY_PHASE1	COMPLETED	Atorvastatin ± Aspirin in Lynch Syndrome Syndrome
NCT04906382	EARLY_PHASE1	TERMINATED	Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer
NCT00508573	Not specified	COMPLETED	Registry for Women Who Are At Risk Or May Have Lynch Syndrome
NCT00582296	Not specified	ACTIVE_NOT_RECRUITING	Multi-Organ Screening Recommendations in Patients With Lynch Syndrome
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT00633607	Not specified	COMPLETED	Hereditary Colorectal and Associated Tumor Registry Study
NCT00905710	Not specified	COMPLETED	Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome
NCT00927680	Not specified	UNKNOWN	Familial Colorectal Cancer Registry in Hispanics
NCT01199250	Not specified	WITHDRAWN	Biomarkers in Samples From Patients With Endometrial Cancer
NCT01216930	Not specified	COMPLETED	Molecular Screening for Lynch Syndrome in Southern Denmark
NCT01582841	Not specified	COMPLETED	Integrating Genetic Testing for Lynch Syndrome in a Managed Care Setting
NCT01823471	Not specified	COMPLETED	I-Scan For Colon Polyp Detection In HNPCC
NCT01845753	Not specified	COMPLETED	Molecular Screening for Lynch Syndrome in Denmark
NCT01850654	Not specified	COMPLETED	Ohio Colorectal Cancer Prevention Initiative
NCT02012699	Not specified	RECRUITING	Integrated Cancer Repository for Cancer Research
NCT02053805	Not specified	UNKNOWN	Prostate Cancer Screening Among Men With High Risk Genetic Predisposition
NCT02194387	Not specified	ACTIVE_NOT_RECRUITING	Energy Balance Interventions in Increasing Physical Activity in Breast Cancer Gene Positive Patients, Lynch Syndrome-Positive Patients, CLL Survivors or High-Risk Family Members
NCT02198092	Not specified	COMPLETED	Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT02371135	Not specified	ACTIVE_NOT_RECRUITING	Metagenomic Evaluation of the Gut Microbiome in Patients With Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes
NCT02494791	Not specified	UNKNOWN	Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer