RPRML

Summary

RPRML (reprimo like, HGNC:32422) is a protein-coding gene on chromosome 17q21.32, encoding Reprimo-like protein (Q8N4K4).

Predicted to be located in membrane.

Source: NCBI Gene 388394 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_203400

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32422
Approved symbol	RPRML
Name	reprimo like
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	MGC43894
Ensembl gene	ENSG00000179673
Ensembl biotype	protein_coding
Entrez	388394

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000322329

RefSeq mRNA: 1 — MANE Select: NM_203400 NM_203400

CCDS: CCDS11508

Canonical transcript exons

ENST00000322329 — 1 exons

Exon	Start	End
ENSE00001263596	46978156	46979253

Expression profiles

Bgee: expression breadth ubiquitous, 114 present calls, max score 88.40.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0691 / max 125.3192, expressed in 200 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166589	0.9070	189
166590	0.1621	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	88.40	gold quality
putamen	UBERON:0001874	87.09	gold quality
caudate nucleus	UBERON:0001873	86.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.00	gold quality
primary visual cortex	UBERON:0002436	83.58	gold quality
endothelial cell	CL:0000115	82.92	silver quality
right frontal lobe	UBERON:0002810	82.43	gold quality
anterior cingulate cortex	UBERON:0009835	81.07	gold quality
middle temporal gyrus	UBERON:0002771	80.94	silver quality
prefrontal cortex	UBERON:0000451	80.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.28	silver quality
frontal cortex	UBERON:0001870	80.10	gold quality
neocortex	UBERON:0001950	79.86	gold quality
cerebral cortex	UBERON:0000956	78.63	gold quality
superior frontal gyrus	UBERON:0002661	77.48	gold quality
occipital lobe	UBERON:0002021	76.93	gold quality
amygdala	UBERON:0001876	76.00	gold quality
forebrain	UBERON:0001890	75.06	gold quality
temporal lobe	UBERON:0001871	74.49	gold quality
postcentral gyrus	UBERON:0002581	74.49	silver quality
buccal mucosa cell	CL:0002336	74.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.14	gold quality
tendon of biceps brachii	UBERON:0008188	73.83	silver quality
brain	UBERON:0000955	73.02	gold quality
cerebellar cortex	UBERON:0002129	72.66	gold quality
cerebellar hemisphere	UBERON:0002245	72.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	72.25	silver quality
parietal lobe	UBERON:0001872	71.92	silver quality
cerebellum	UBERON:0002037	71.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	129.08
E-ANND-3	no	2.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting RPRML, 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-8485	100.00	77.57	4731
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-1972	97.67	67.38	1172

Literature-anchored findings (GeneRIF, showing 3)

• 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)
• Our results suggest that RPRML is a TSG, downregulated by DNA methylation in GC, and that circulating methylated RPRML DNA can distinguish patients with GC from cancer-free controls. Thus, these findings provide justification for larger clinical studies to further assess its value in multi-biomarker panel approaches for non-invasive diagnosis of GC. (PMID:33322837)
• The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer. (PMID:33322837)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rprml	ENSDARG00000056768
mus_musculus	Rprml	ENSMUSG00000046215
rattus_norvegicus	Rprml	ENSRNOG00000028436

Paralogs (1): RPRM (ENSG00000177519)

Protein

Protein identifiers

Reprimo-like protein — Q8N4K4 (reviewed: Q8N4K4)

All UniProt accessions (1): Q8N4K4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the reprimo family.

RefSeq proteins (1): NP_981945* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043383	Reprimo_fam	Family

UniProt features (3 total): chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4K4-F1	59.23	0.04

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): 109

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): BENPORATH_ES_WITH_H3K27ME3, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, CAHOY_NEURONAL, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_129_MOUSE_DN, GSE5503_PLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, ZSCAN30_TARGET_GENES, MIR5688, MIR495_3P, GSE10239_KLRG1INT_VS_KLRG1HIGH_EFF_CD8_TCELL_UP, MIR532_3P, GSE13229_MATURE_VS_INTMATURE_NKCELL_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPRML	NRN1L	Q496H8	526
RPRML	CPLANE2	Q9BU20	406
RPRML	PLXDC1	Q8IUK5	364
RPRML	PLA2G4F	Q68DD2	355
RPRML	PLA2G4D	Q86XP0	336
RPRML	ACTR8	Q9H981	336
RPRML	NPW	Q8N729	328
RPRML	RNF180	Q86T96	324
RPRML	PIGC	Q92535	323
RPRML	PLAC1	Q9HBJ0	300
RPRML	ARHGEF19	Q8IW93	295
RPRML	COL25A1	Q9BXS0	293
RPRML	RPS13	P19116	285
RPRML	PROKR1	Q8TCW9	282
RPRML	SLF1	Q9BQI6	280

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ERBB2	RPRML	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): RPRML (Two-hybrid)

ESM2 similar proteins: A0A5F4BST2, A5PJC7, A8MWV9, D3ZZP4, O14836, P0CAN6, P11911, P11912, P14753, Q01114, Q07303, Q13113, Q2KI80, Q2KL21, Q3TS39, Q3URD2, Q4V9L6, Q5F267, Q5FVJ4, Q5FVQ7, Q5RA41, Q5T1S8, Q6P9G4, Q6UWJ8, Q6UX34, Q80VJ8, Q810F0, Q86XR5, Q8BRJ3, Q8BX43, Q8K064, Q8K5A9, Q8N112, Q8N4K4, Q8N6L0, Q8NBR0, Q8NC24, Q8QZT4, Q8R138, Q923S2

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

273 predictions. Top by Δscore:

Variant	Effect	Δscore
17:46978970:T:TA	donor_gain	0.9700
17:46978993:G:GT	donor_gain	0.8700
17:46978994:A:T	donor_gain	0.8600
17:46978747:C:CT	acceptor_gain	0.8100
17:46979083:G:T	donor_gain	0.8100
17:46978822:CAGG:C	donor_gain	0.7700
17:46978747:C:T	acceptor_gain	0.7000
17:46978748:A:T	acceptor_gain	0.6900
17:46978965:C:CT	donor_gain	0.6600
17:46978966:C:CT	donor_gain	0.6600
17:46978772:G:GG	donor_gain	0.6500
17:46978767:CCACG:C	donor_loss	0.6400
17:46978768:CACG:C	donor_loss	0.6400
17:46978769:ACGGT:A	donor_loss	0.6400
17:46978770:CGGTA:C	donor_loss	0.6400
17:46978772:GT:G	donor_loss	0.6400
17:46978773:T:A	donor_loss	0.6400
17:46978774:A:C	donor_loss	0.6400
17:46978964:TCC:T	donor_gain	0.6300
17:46978914:GCCC:G	donor_gain	0.6200
17:46979113:C:CA	donor_gain	0.6000
17:46978971:C:A	donor_gain	0.5900
17:46978776:G:C	donor_loss	0.5800
17:46978909:G:A	donor_gain	0.5800
17:46978885:C:CA	donor_gain	0.5700
17:46978998:T:TA	donor_gain	0.5700
17:46978418:CCCCA:C	donor_gain	0.5500
17:46978775:A:AC	donor_loss	0.5400
17:46978930:T:A	donor_gain	0.5400
17:46979229:G:GT	donor_gain	0.5400

AlphaMissense

758 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:46978760:C:T	G83D	0.998
17:46978788:A:G	C74R	0.997
17:46978736:A:G	L91P	0.996
17:46978746:C:G	G88R	0.996
17:46978761:C:G	G83R	0.996
17:46978796:G:T	A71D	0.996
17:46978745:C:T	G88D	0.994
17:46978775:A:T	L78H	0.994
17:46978781:A:T	L76Q	0.994
17:46978762:G:C	F82L	0.992
17:46978762:G:T	F82L	0.992
17:46978764:A:G	F82L	0.992
17:46978750:G:C	F86L	0.991
17:46978750:G:T	F86L	0.991
17:46978752:A:G	F86L	0.991
17:46978781:A:G	L76P	0.991
17:46978743:A:G	C89R	0.990
17:46978775:A:C	L78R	0.990
17:46978781:A:C	L76R	0.990
17:46978757:A:T	V84D	0.989
17:46978775:A:G	L78P	0.989
17:46978769:A:T	V80E	0.987
17:46978772:G:T	T79N	0.987
17:46978793:A:T	V72E	0.986
17:46978738:G:C	N90K	0.984
17:46978738:G:T	N90K	0.984
17:46978726:C:A	K94N	0.983
17:46978726:C:G	K94N	0.983
17:46978748:A:T	L87Q	0.982
17:46978784:A:T	V75E	0.982

dbSNP variants (sampled 300 via entrez): RS1002579657 (17:46980757 C>T), RS1002936054 (17:46980848 A>G), RS1003120786 (17:46979760 T>A,G), RS1003487112 (17:46980864 GA>G,GAA), RS1003561501 (17:46979514 T>G), RS1005189101 (17:46980846 T>A), RS1005446196 (17:46978691 C>A,G), RS1005471645 (17:46980754 A>C,T), RS1006637958 (17:46980318 TTCTTCCTTCTCC>T), RS1007098947 (17:46980954 C>T), RS1008714509 (17:46979889 G>A), RS1009326365 (17:46981227 A>G,T), RS1009387686 (17:46979034 G>C,T), RS1010665831 (17:46979405 T>G), RS1010679109 (17:46979360 C>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_16	Body mass index	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	8
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
aristolochic acid I	increases expression	1
decabromobiphenyl ether	affects expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
ferrous chloride	decreases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cytarabine	increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Silicon Dioxide	increases expression	1
Thapsigargin	decreases expression	1

Clinical trials (associated diseases)

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