RPRM

Summary

RPRM (reprimo, TP53 dependent G2 arrest mediator homolog, HGNC:24201) is a protein-coding gene on chromosome 2q23.3, encoding Protein reprimo (Q9NS64). May be involved in the regulation of p53-dependent G2 arrest of the cell cycle.

Predicted to be involved in regulation of mitotic cell cycle. Predicted to act upstream of or within regulation of cell cycle. Predicted to be located in membrane. Predicted to be active in cytoplasm.

Source: NCBI Gene 56475 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_019845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24201
Approved symbol	RPRM
Name	reprimo, TP53 dependent G2 arrest mediator homolog
Location	2q23.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90327, REPRIMO
Ensembl gene	ENSG00000177519
Ensembl biotype	protein_coding
OMIM	612171
Entrez	56475

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000325926

RefSeq mRNA: 1 — MANE Select: NM_019845 NM_019845

CCDS: CCDS2198

Canonical transcript exons

ENST00000325926 — 1 exons

Exon	Start	End
ENSE00001287926	153477338	153478762

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 95.49.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1348 / max 272.0495, expressed in 540 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31324	1.8922	437
31323	0.6904	268
31325	0.5523	242

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.49	gold quality
cauda epididymis	UBERON:0004360	88.80	gold quality
adenohypophysis	UBERON:0002196	86.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.45	gold quality
body of uterus	UBERON:0009853	85.88	gold quality
nasal cavity epithelium	UBERON:0005384	85.40	gold quality
left adrenal gland cortex	UBERON:0035825	84.40	gold quality
left adrenal gland	UBERON:0001234	84.36	gold quality
prefrontal cortex	UBERON:0000451	83.50	gold quality
amygdala	UBERON:0001876	83.39	gold quality
endocervix	UBERON:0000458	82.98	gold quality
pituitary gland	UBERON:0000007	82.93	gold quality
right adrenal gland cortex	UBERON:0035827	82.75	gold quality
right adrenal gland	UBERON:0001233	82.66	gold quality
adrenal cortex	UBERON:0001235	82.55	gold quality
orbitofrontal cortex	UBERON:0004167	82.29	gold quality
myometrium	UBERON:0001296	81.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.81	gold quality
secondary oocyte	CL:0000655	80.67	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	80.67	gold quality
adrenal gland	UBERON:0002369	80.07	gold quality
frontal cortex	UBERON:0001870	79.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.95	gold quality
neocortex	UBERON:0001950	79.81	gold quality
hypothalamus	UBERON:0001898	79.71	gold quality
anterior cingulate cortex	UBERON:0009835	79.41	gold quality
cingulate cortex	UBERON:0003027	79.31	gold quality
right uterine tube	UBERON:0001302	78.93	gold quality
temporal lobe	UBERON:0001871	78.63	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	529.48
E-HCAD-10	yes	28.08
E-ANND-3	no	1.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, FOXA1, TCF12, TCF3, TP53

miRNA regulators (miRDB)

38 targeting RPRM, 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-5692A	100.00	74.40	6850
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-3184-5P	98.56	67.13	1491

Literature-anchored findings (GeneRIF, showing 18)

• Results suggest that aberrant methylation of Reprimo is a common event in pancreatic carcinogenesis and is associated with genetic instability. (PMID:16752411)
• An association between the Reprimo 824G>C heterozygote and diverticular disease may exist on the basis of deviation from Hardy-Weinberg equilibrium. (PMID:18197409)
• Aberrant hypermethylation of Reprimo is high in primary gastric cancer as well as in pair plasma samples. In plasma from asymptomatic controls, Reprimo is infrequently methylated. Reprimo is a potential biomarker for early detection of gastric cancer. (PMID:18829507)
• these data implicate a novel role for HDAC7 and FoxA1 in estrogen repression of RPRM. (PMID:19917725)
• Loss of Reprimo and S100A2 expressions occurs frequently in gastric adenocarcinomas. The expressions of Reprimo and S100A2 may be potential biomarkers for gastric adenocarcinomas detection. (PMID:20949468)
• RPRM is transiently up-regulated at a posttranscriptional level in times of cellular stress to restrict cell survival, proliferation, and tumor formation (PMID:22562171)
• study concludes that LMP-1 may induce cell cycle arrest at G(2)/M progression via upregulation of 14-3-3sigma and Reprimo (PMID:23312294)
• Reprimo expression is normally induced in response to DNA damage, acting as a novel tumor suppressor in gastric cancer; however, Reprimo methylation abrogates its expression and effects (PMID:23982217)
• tp53-dependent G2 arrest mediator candidate gene, Reprimo, is down-regulated by promoter hypermethylation in pediatric acute myeloid leukemia (PMID:25629980)
• Loss of expression of Reprimo (RPRM), a p53-induced cell cycle arrest gene correlates with invasive stage of tumor progression and p73 expression in gastric cancer. These findings suggest that other members of the p53 gene family may participate in the regulation of RPRM expression (PMID:25954972)
• Positive association between RPRM and p73 expression suggest that other members of the p53 gene family may participate in the regulation of RPRM expression. (PMID:25954972)
• The DNA methylation of both Reprimo and hMLH1 genes depressed the protein expression, and may participate in the occurrence and progression and gastric cancer (PMID:26823831)
• Results provide evidence that RPRM promoter methylation is highly associated with gastric cancer. (PMID:27992600)
• tissue-specific expression patterns of the RPRM transcripts and protein are conserved between zebrafish and humans. We propose the zebrafish as a powerful tool to elucidate the both physiological and pathological roles of the RPRM gene family (PMID:28562620)
• data suggest that ERalpha expression in breast cancer may affect the DNA methylation of CpG-island in the RPRM gene. (PMID:28809778)
• Reprimo methylation was found more frequently in malignant intraductal papillary mucinous neoplasm (IPMN), suggesting reprimo methylation is involved in malignant transformation of IPMNs. (PMID:29401170)
• rawing on embryonic and adult expression patterns, we address the potential relevance of RPRM and RPRML in cancer. Active investigation or analytical research in the coming years should contribute to novel translational applications of this poorly understood gene family as potential biomarkers and development of novel cancer therapies. (PMID:29941787)
• Downregulated Reprimo by LINC00467 participates in the growth and metastasis of gastric cancer. (PMID:35549646)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rprmb	ENSDARG00000024006
danio_rerio	rprma	ENSDARG00000053383
mus_musculus	Rprm	ENSMUSG00000075334
rattus_norvegicus	Rprm	ENSRNOG00000005109

Paralogs (1): RPRML (ENSG00000179673)

Protein

Protein identifiers

Protein reprimo — Q9NS64 (reviewed: Q9NS64)

All UniProt accessions (1): Q9NS64

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the regulation of p53-dependent G2 arrest of the cell cycle. Seems to induce cell cycle arrest by inhibiting CDK1 activity and nuclear translocation of the CDC2 cyclin B1 complex.

Subcellular location. Cytoplasm. Membrane.

Induction. By p53/TP53, following X-ray irradiation.

Miscellaneous. ‘Reprimo’ signifies stop/repress.

Similarity. Belongs to the reprimo family.

RefSeq proteins (1): NP_062819* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043383	Reprimo_fam	Family

UniProt features (5 total): glycosylation site 2, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS64-F1	61.09	0.10

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): 98

Glycosylation sites (2): 7, 18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, MODULE_255, GOZGIT_ESR1_TARGETS_DN, MODULE_317, SASSON_RESPONSE_TO_FORSKOLIN_DN, GOBP_REGULATION_OF_CELL_CYCLE, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_MITOTIC_CELL_CYCLE, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, PACHER_TARGETS_OF_IGF1_AND_IGF2_UP, SASSON_RESPONSE_TO_GONADOTROPHINS_DN, CAIRO_LIVER_DEVELOPMENT_UP, MASSARWEH_TAMOXIFEN_RESISTANCE_UP

GO Biological Process (2): regulation of mitotic cell cycle (GO:0007346), regulation of cell cycle (GO:0051726)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
mitotic cell cycle	1
regulation of cell cycle	1
cell cycle	1
regulation of cellular process	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPRM	CCNB1	P14635	748
RPRM	TP53	P04637	617
RPRM	NPBWR2	P48146	458
RPRM	PTGS2	P35354	457
RPRM	GADD45A	P24522	431
RPRM	NPB	Q8NG41	408
RPRM	RASSF1	Q9NS23	401
RPRM	TMEM74	Q96NL1	396
RPRM	SFN	P31947	394
RPRM	MGMT	P16455	388
RPRM	TAL2	Q16559	383
RPRM	RUNX3	Q13761	380
RPRM	CDKN2A	P42771	378
RPRM	PIDD1	Q9HB75	378
RPRM	PERP	Q96FX8	377

IntAct

249 interactions, top by confidence:

A	B	Type	Score
FATE1	RPRM	psi-mi:“MI:0915”(physical association)	0.720
TMEM79	RPRM	psi-mi:“MI:0915”(physical association)	0.720
CLEC17A	RPRM	psi-mi:“MI:0915”(physical association)	0.600
MS4A4A	RPRM	psi-mi:“MI:0915”(physical association)	0.600
RPRM	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
RPRM	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
RPRM	GJB3	psi-mi:“MI:0915”(physical association)	0.560
RPRM	AQP6	psi-mi:“MI:0915”(physical association)	0.560
RPRM	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
RPRM	HHLA2	psi-mi:“MI:0915”(physical association)	0.560
RPRM	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
BNIP3	RPRM	psi-mi:“MI:0915”(physical association)	0.560
MPP1	RPRM	psi-mi:“MI:0915”(physical association)	0.560
EHHADH	RPRM	psi-mi:“MI:0915”(physical association)	0.560
RPRM	GNG13	psi-mi:“MI:0915”(physical association)	0.560
PBX3	RPRM	psi-mi:“MI:0915”(physical association)	0.560
LPAR6	RPRM	psi-mi:“MI:0915”(physical association)	0.560
FBXL19	RPRM	psi-mi:“MI:0915”(physical association)	0.560
PLEKHF2	RPRM	psi-mi:“MI:0915”(physical association)	0.560
WDFY2	RPRM	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (102): TMEM79 (Two-hybrid), FATE1 (Two-hybrid), RPRM (Two-hybrid), RPRM (Two-hybrid), CUL1 (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), CDK4 (Affinity Capture-MS), RPRM (Affinity Capture-MS), RPRM (Affinity Capture-MS), RPRM (Two-hybrid), RPRM (Two-hybrid), RPRM (Two-hybrid), RPRM (Two-hybrid), RPRM (Two-hybrid), RPRM (Two-hybrid)

ESM2 similar proteins: A4IG66, A5PLA0, A9ZLX4, D3Z1Q2, D3ZZP4, D5K8A9, F1M2Z5, O14525, P0C2L3, P0DKX4, Q08DP3, Q08EA8, Q13145, Q1LVN1, Q1RMT2, Q2F7Z7, Q3MHM8, Q3T0Q2, Q3URD2, Q4R8C8, Q502I1, Q58CU5, Q5BJN9, Q5R800, Q5RA41, Q5XJS0, Q5ZKK0, Q61137, Q6GM22, Q6PBK8, Q8BPM6, Q8C4Q9, Q8HYZ0, Q8IUW5, Q8K2J7, Q8N4K4, Q8N6S5, Q8NEA5, Q91XN4, Q96G30

Diamond homologs: A5PLA0, Q1RMT2, Q3URD2, Q502I1, Q5BJN9, Q6GM22, Q6PBK8, Q8N4K4, Q9JJ72, Q9NS64

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	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

63 predictions. Top by Δscore:

Variant	Effect	Δscore
2:153478267:T:TA	donor_gain	0.6700
2:153478261:TC:T	donor_gain	0.5300
2:153478262:CC:C	donor_gain	0.5300
2:153477657:T:C	donor_gain	0.4400
2:153478102:T:A	donor_gain	0.4100
2:153478263:C:CT	donor_gain	0.4100
2:153477976:T:TA	donor_gain	0.3900
2:153478009:G:A	donor_gain	0.3700
2:153477686:CAAA:C	donor_gain	0.3600
2:153477687:AAAA:A	donor_gain	0.3600
2:153477684:CACA:C	donor_gain	0.3400
2:153477685:ACAA:A	donor_gain	0.3400
2:153477689:A:T	donor_gain	0.3400
2:153477706:CG:C	donor_gain	0.3400
2:153478105:G:T	acceptor_gain	0.3400
2:153478253:C:CT	donor_gain	0.3300
2:153477913:ACCTG:A	donor_gain	0.3100
2:153477914:CCTGC:C	donor_gain	0.3100
2:153477606:A:C	donor_gain	0.3000
2:153477688:AA:A	donor_gain	0.3000
2:153477912:CACCT:C	donor_gain	0.3000
2:153478104:C:CT	acceptor_gain	0.2900
2:153477656:A:AC	donor_gain	0.2800
2:153478098:T:TA	donor_gain	0.2800
2:153478254:C:CT	donor_gain	0.2800
2:153477909:GCCCA:G	donor_gain	0.2700
2:153477910:CCCAC:C	donor_gain	0.2700
2:153477911:CCACC:C	donor_gain	0.2700
2:153478217:C:CT	acceptor_gain	0.2700
2:153477614:T:TA	donor_gain	0.2600

AlphaMissense

706 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:153478351:C:T	G72D	1.000
2:153478372:A:T	L65H	1.000
2:153478327:A:G	L80P	0.999
2:153478337:C:G	G77R	0.999
2:153478352:C:G	G72R	0.999
2:153478353:G:C	F71L	0.999
2:153478353:G:T	F71L	0.999
2:153478355:A:G	F71L	0.999
2:153478366:A:G	L67P	0.999
2:153478366:A:T	L67H	0.999
2:153478372:A:G	L65P	0.999
2:153478379:A:G	C63R	0.999
2:153478387:G:T	A60E	0.999
2:153478317:C:A	K83N	0.998
2:153478317:C:G	K83N	0.998
2:153478334:A:G	C78R	0.998
2:153478336:C:T	G77D	0.998
2:153478339:A:T	L76H	0.998
2:153478341:G:C	F75L	0.998
2:153478341:G:T	F75L	0.998
2:153478343:A:G	F75L	0.998
2:153478360:A:T	V69E	0.998
2:153478366:A:C	L67R	0.998
2:153478372:A:C	L65R	0.998
2:153478384:A:T	V61D	0.998
2:153478316:A:G	S84P	0.997
2:153478324:A:G	L81P	0.997
2:153478327:A:T	L80Q	0.997
2:153478329:A:C	N79K	0.997
2:153478329:A:T	N79K	0.997

dbSNP variants (sampled 300 via entrez): RS1000435194 (2:153477237 C>G,T), RS1000527137 (2:153480501 C>T), RS1003023147 (2:153478700 A>C), RS1004359758 (2:153479670 C>T), RS1004433347 (2:153479424 G>A), RS1004504779 (2:153479205 T>A,C), RS1004792732 (2:153479532 C>G), RS1005240395 (2:153478089 C>G), RS1007347878 (2:153479635 C>G,T), RS1007644121 (2:153479899 T>C), RS1007722783 (2:153477407 A>G), RS1009022788 (2:153477000 G>T), RS1009354917 (2:153477050 C>G,T), RS1009647646 (2:153477292 C>T), RS1009744450 (2:153480620 G>C,T)

Disease associations

OMIM: gene MIM:612171 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002040_4	Blood trace element (Zn levels)	5.000000e-06
GCST004748_71	Lung cancer	4.000000e-06
GCST005025_34	Anti-saccade response	9.000000e-07
GCST006979_42	Heel bone mineral density	4.000000e-09
GCST012303_5	Recurrent major depressive disorder x sex interaction	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006874	antisaccade response measurement
EFO:0009270	heel bone mineral density
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	8
Estradiol	affects cotreatment, decreases expression, increases expression	4
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
methylmercuric chloride	increases expression	1
naringenin	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression, decreases reaction	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	increases activity, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Vitamin E	increases expression	1
Mifepristone	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2E4	Abcam HeLa RPRM KO	Cancer cell line	Female

Clinical trials (associated diseases)

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