RTP4

Summary

RTP4 (receptor transporter protein 4, HGNC:23992) is a protein-coding gene on chromosome 3q27.3, encoding Receptor-transporting protein 4 (Q96DX8). Chaperone protein that facilitates the trafficking and functional cell surface expression of some G-protein coupled receptors (GPCRs).

Predicted to enable olfactory receptor binding activity. Involved in detection of chemical stimulus involved in sensory perception of bitter taste and protein targeting to membrane. Located in cytoplasm.

Source: NCBI Gene 64108 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_022147

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23992
Approved symbol	RTP4
Name	receptor transporter protein 4
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Aliases	IFRG28, Z3CXXC4
Ensembl gene	ENSG00000136514
Ensembl biotype	protein_coding
OMIM	609350
Entrez	64108

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000259030

RefSeq mRNA: 1 — MANE Select: NM_022147 NM_022147

CCDS: CCDS33910

Canonical transcript exons

ENST00000259030 — 2 exons

Exon	Start	End
ENSE00000924358	187368385	187368596
ENSE00001079667	187370788	187372076

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 83.62.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3458 / max 313.1952, expressed in 812 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40380	4.1746	811
40381	0.1712	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	83.62	gold quality
nasopharynx	UBERON:0001728	83.60	gold quality
bronchial epithelial cell	CL:0002328	83.58	gold quality
palpebral conjunctiva	UBERON:0001812	82.70	gold quality
monocyte	CL:0000576	82.36	gold quality
leukocyte	CL:0000738	82.04	gold quality
mononuclear cell	CL:0000842	81.99	gold quality
epithelium of bronchus	UBERON:0002031	81.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.55	gold quality
granulocyte	CL:0000094	81.40	gold quality
bronchus	UBERON:0002185	80.89	gold quality
pancreatic ductal cell	CL:0002079	80.11	silver quality
nasal cavity epithelium	UBERON:0005384	80.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.92	gold quality
jejunal mucosa	UBERON:0000399	78.98	gold quality
nasal cavity mucosa	UBERON:0001826	78.47	gold quality
duodenum	UBERON:0002114	78.20	gold quality
germinal epithelium of ovary	UBERON:0001304	77.73	gold quality
gall bladder	UBERON:0002110	77.25	gold quality
spleen	UBERON:0002106	76.94	gold quality
rectum	UBERON:0001052	76.64	gold quality
decidua	UBERON:0002450	75.58	silver quality
right uterine tube	UBERON:0001302	74.97	gold quality
lymph node	UBERON:0000029	74.82	gold quality
apex of heart	UBERON:0002098	74.57	gold quality
mucosa of transverse colon	UBERON:0004991	74.18	gold quality
blood	UBERON:0000178	73.99	gold quality
stromal cell of endometrium	CL:0002255	73.69	gold quality
islet of Langerhans	UBERON:0000006	73.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-HCAD-30	no	69.07
E-ANND-3	no	3.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting RTP4, 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-4496	99.88	68.89	2236
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-6069	97.45	65.88	357

Literature-anchored findings (GeneRIF, showing 3)

• RTP4 inhibits IFN-I response and enhances experimental cerebral malaria and neuropathology. (PMID:32709745)
• RTP4 is a novel prognosis-related hub gene in cutaneous melanoma. (PMID:34154655)
• RTP4 silencing provokes tumor-intrinsic resistance to immune checkpoint blockade in colorectal cancer. (PMID:36859628)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rtp4	ENSMUSG00000033355
rattus_norvegicus	Rtp4	ENSRNOG00000066242

Paralogs (4): RTP3 (ENSG00000163825), RTP1 (ENSG00000175077), RTP5 (ENSG00000188011), RTP2 (ENSG00000198471)

Protein

Protein identifiers

Receptor-transporting protein 4 — Q96DX8 (reviewed: Q96DX8)

Alternative names: 28 kDa interferon-responsive protein, 3CxxC-type zinc finger protein 4

All UniProt accessions (1): Q96DX8

UniProt curated annotations — full annotation on UniProt →

Function. Chaperone protein that facilitates the trafficking and functional cell surface expression of some G-protein coupled receptors (GPCRs). Promotes functional expression of the bitter taste receptor TAS2R16. Also promotes functional expression of the opioid receptor heterodimer OPRD1-OPRM1. In addition, acts as a potent IFN-inducible suppressor of pathogens including lyssavirus rabies, influenza A or yellow fever virus. Mechanistically, associates with the viral replicase, binds viral RNA, and thereby suppresses viral genome amplification that replicates at the endoplasmic reticulum. In addition, restores antiviral signaling by interacting with and sequestering influenza A virus protein NS1.

Subunit / interactions. Interacts with TASR16. Interacts with OPRD1 and OPRM1; the interaction promotes cell surface localization of the OPDR1-OPRM1 heterodimer. (Microbial infection) Interacts with influenza A virus protein NS1; this interaction sequesters NS1 from interacting with RIG-I/DDX58 to restore antiviral signaling.

Subcellular location. Membrane. Cytoplasm.

Tissue specificity. Expressed in circumvallate papillae and testis.

Induction. By interferons. Upon influenza virus infection.

Similarity. Belongs to the TMEM7 family.

RefSeq proteins (1): NP_071430* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026096	R-trans_p	Family
IPR027377	ZAR1/RTP1-5-like_Znf-3CxxC	Domain

Pfam: PF13695

UniProt features (14 total): sequence conflict 4, mutagenesis site 4, sequence variant 2, chain 1, topological domain 1, transmembrane region 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DX8-F1	79.57	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (4):

Position	Phenotype
55	loss of interaction with influenza virus ns1.
93	loss of interaction with influenza virus ns1.
149	almost complete loss of influenza na viral rna binding and loss of interaction with influenza virus ns1.
154	complete loss of influenza na viral rna binding and loss of interaction with influenza virus ns1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 311 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_PROTEIN_TARGETING, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, MARTINEZ_RB1_TARGETS_UP, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_DETECTION_OF_CHEMICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_TASTE, GOBP_SENSORY_PERCEPTION_OF_TASTE, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, KOKKINAKIS_METHIONINE_DEPRIVATION_48HR_UP, ZHAN_MULTIPLE_MYELOMA_LB_DN, IRF_Q6

GO Biological Process (4): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), protein targeting to membrane (GO:0006612), protein insertion into membrane (GO:0051205), defense response to virus (GO:0051607)

GO Molecular Function (4): zinc ion binding (GO:0008270), olfactory receptor binding (GO:0031849), protein binding (GO:0005515), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
establishment of protein localization to membrane	2
cellular anatomical structure	2
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
protein targeting	1
intracellular protein localization	1
membrane organization	1
defense response	1
response to virus	1
transition metal ion binding	1
G protein-coupled receptor binding	1
binding	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RTP4	IFI44	Q8TCB0	739
RTP4	USP18	Q9UMW8	736
RTP4	ISG15	P05161	703
RTP4	IFIT3	O14879	685
RTP4	RSAD2	Q8WXG1	673
RTP4	MX1	P20591	647
RTP4	GBP1	P32455	644
RTP4	IFITM3	Q01628	604
RTP4	IRF9	Q00978	590
RTP4	SPATS2L	Q9NUQ6	565
RTP4	IFIT1	P09914	557
RTP4	OASL	Q15646	538
RTP4	PARP14	Q460N5	538
RTP4	HERC6	Q8IVU3	533
RTP4	RIGI	O95786	527

IntAct

21 interactions, top by confidence:

A	B	Type	Score
NRM	RTP4	psi-mi:“MI:0915”(physical association)	0.560
RTP4	DERL3	psi-mi:“MI:0915”(physical association)	0.560
RTP4	TAS2R10	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	RTP4	psi-mi:“MI:0915”(physical association)	0.560
RTP4	REEP4	psi-mi:“MI:0915”(physical association)	0.560
DYNC1H1	RTP4	psi-mi:“MI:0915”(physical association)	0.560
RTP4	OPRM1	psi-mi:“MI:0915”(physical association)	0.370
RTP4	SDHB	psi-mi:“MI:0914”(association)	0.350
TUSC5	RTP4	psi-mi:“MI:0915”(physical association)	0.000
DERL3	RTP4	psi-mi:“MI:0915”(physical association)	0.000
TAS2R10	RTP4	psi-mi:“MI:0915”(physical association)	0.000
RTP4	REEP4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): RTP4 (Two-hybrid), RTP4 (Two-hybrid), REEP4 (Two-hybrid), TUSC5 (Two-hybrid), RTP4 (Two-hybrid), SDHA (Affinity Capture-MS), SDHB (Affinity Capture-MS), RNF41 (Affinity Capture-MS), TMEM245 (Affinity Capture-MS), RTP4 (Affinity Capture-MS), RTP4 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1L8HJK9, A0A2R8QHQ6, A1BPI0, A2AQ14, A2CI98, A2CJ06, C3VD30, O55034, P03122, P11299, P22159, P56645, P59025, Q32L09, Q3T191, Q3UIR3, Q3UPF5, Q497M3, Q5E9L4, Q5EA86, Q5QGT7, Q5R8D5, Q5TKR9, Q5XIX0, Q68FS7, Q6Y2X3, Q7Z2W4, Q80ZA7, Q80ZI2, Q8BV79, Q8BZ21, Q8C8C1, Q8IXX5, Q8K3Y6, Q8N0W7, Q8NC06, Q8ND61, Q8WML3, Q921R4, Q92794

Diamond homologs: P59025, Q5QGT7, Q5QGU6, Q80ZI2, Q8C8C1, Q95JK0, Q96DX8, Q14D33, Q9BQQ7, Q9ER80

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

364 predictions. Top by Δscore:

Variant	Effect	Δscore
3:187368565:TGG:T	donor_gain	0.9900
3:187368592:GGCTG:G	donor_gain	0.9900
3:187368593:GCTG:G	donor_gain	0.9900
3:187368593:GCTGG:G	donor_gain	0.9900
3:187368595:TGG:T	donor_loss	0.9900
3:187368597:G:GG	donor_gain	0.9900
3:187368597:GTGA:G	donor_loss	0.9900
3:187368598:T:A	donor_loss	0.9900
3:187370107:T:TA	acceptor_gain	0.9900
3:187370108:G:A	acceptor_gain	0.9900
3:187370106:AT:A	acceptor_gain	0.9800
3:187370106:ATG:A	acceptor_gain	0.9800
3:187370107:T:G	acceptor_gain	0.9800
3:187370782:CTGCA:C	acceptor_loss	0.9800
3:187370783:TGCA:T	acceptor_loss	0.9800
3:187370784:GCAGG:G	acceptor_loss	0.9800
3:187370785:CAGG:C	acceptor_loss	0.9800
3:187370786:A:AG	acceptor_gain	0.9800
3:187370786:AGG:A	acceptor_loss	0.9800
3:187370787:G:GG	acceptor_gain	0.9800
3:187368594:CTG:C	donor_gain	0.9700
3:187368599:G:GG	donor_loss	0.9700
3:187370779:T:TA	acceptor_gain	0.9600
3:187370779:T:A	acceptor_loss	0.9500
3:187368595:TG:T	donor_gain	0.9400
3:187368596:GG:G	donor_gain	0.9400
3:187368601:GT:G	donor_gain	0.9400
3:187368567:G:GT	donor_gain	0.9300
3:187370106:A:AG	acceptor_gain	0.9200
3:187370117:CAATG:C	acceptor_gain	0.9200

AlphaMissense

1607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:187370789:T:C	F53L	0.992
3:187370791:C:A	F53L	0.992
3:187370791:C:G	F53L	0.992
3:187370948:T:C	F106L	0.988
3:187370950:C:A	F106L	0.988
3:187370950:C:G	F106L	0.988
3:187370818:G:C	W62C	0.984
3:187370818:G:T	W62C	0.984
3:187370949:T:C	F106S	0.982
3:187368514:T:A	W25R	0.978
3:187368514:T:C	W25R	0.978
3:187368589:T:C	F50L	0.978
3:187368591:T:A	F50L	0.978
3:187368591:T:G	F50L	0.978
3:187370790:T:C	F53S	0.976
3:187368516:G:C	W25C	0.972
3:187368516:G:T	W25C	0.972
3:187370897:T:C	F89L	0.971
3:187370899:T:A	F89L	0.971
3:187370899:T:G	F89L	0.971
3:187370943:C:A	P104H	0.970
3:187370905:A:C	Q91H	0.969
3:187370905:A:T	Q91H	0.969
3:187370790:T:G	F53C	0.966
3:187370816:T:A	W62R	0.962
3:187370816:T:C	W62R	0.962
3:187370909:T:A	C93S	0.962
3:187370910:G:C	C93S	0.962
3:187370985:T:C	L118P	0.961
3:187370949:T:G	F106C	0.958

dbSNP variants (sampled 300 via entrez): RS1000412394 (3:187368028 G>A), RS1000685460 (3:187367921 A>C), RS1000688214 (3:187369094 T>C), RS1000741574 (3:187369522 T>C), RS1001205774 (3:187368082 C>A,T), RS1001542371 (3:187367751 C>T), RS1002037344 (3:187367860 C>G,T), RS1002961109 (3:187369830 G>C,T), RS1003654011 (3:187371969 T>C), RS1003768812 (3:187372253 C>T), RS1003995 (3:187371243 C>A,T), RS1004409914 (3:187366847 C>T), RS1004598587 (3:187368660 G>T), RS1004652352 (3:187368340 A>G), RS1004760236 (3:187366751 G>A,C,T)

Disease associations

OMIM: gene MIM:609350 | 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
GCST007627_2	Impulsivity (attentional)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006946	behavioural disinhibition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Plant Extracts	increases expression, affects expression, affects reaction	2
Tretinoin	increases expression	2
afuresertib	increases expression	1
sotorasib	affects cotreatment, increases expression	1
alpha phellandrene	increases expression	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Diuron	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	affects expression, affects reaction	1
Methapyrilene	decreases expression, increases methylation	1
Nickel	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1HB	Abcam A-549 RTP4 KO 1	Cancer cell line	Male
CVCL_B2PV	Abcam A-549 RTP4 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

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