RRH

Summary

RRH (retinal pigment epithelium-derived rhodopsin homolog, HGNC:10450) is a protein-coding gene on chromosome 4q25, encoding Visual pigment-like receptor peropsin (O14718). May play a role in rpe physiology either by detecting light directly or by monitoring the concentration of retinoids or other photoreceptor-derived compounds.

Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes opsin 5 and retinal G protein coupled receptor.

Source: NCBI Gene 10692 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_006583

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10450
Approved symbol	RRH
Name	retinal pigment epithelium-derived rhodopsin homolog
Location	4q25
Locus type	gene with protein product
Status	Approved
Aliases	peropsin
Ensembl gene	ENSG00000180245
Ensembl biotype	protein_coding
OMIM	605224
Entrez	10692

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000317735, ENST00000650907, ENST00000652276

RefSeq mRNA: 1 — MANE Select: NM_006583 NM_006583

CCDS: CCDS3687

Canonical transcript exons

ENST00000317735 — 7 exons

Exon	Start	End
ENSE00001237833	109842469	109842647
ENSE00001237837	109837437	109837605
ENSE00001237846	109836007	109836160
ENSE00001237855	109835366	109835465
ENSE00001237863	109833139	109833329
ENSE00001237877	109827972	109828133
ENSE00003902626	109844083	109844942

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 73.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0701 / max 92.6403, expressed in 4 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49247	0.0328	4
49248	0.0243	2
49249	0.0088	3
49246	0.0041	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.19	silver quality
pigmented layer of retina	UBERON:0001782	70.04	gold quality
tibialis anterior	UBERON:0001385	60.20	silver quality
cerebellar cortex	UBERON:0002129	58.63	gold quality
cerebellar hemisphere	UBERON:0002245	58.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	58.49	gold quality
cerebellum	UBERON:0002037	57.29	gold quality
decidua	UBERON:0002450	56.55	gold quality
sperm	CL:0000019	55.11	gold quality
hair follicle	UBERON:0002073	55.10	gold quality
prefrontal cortex	UBERON:0000451	55.06	gold quality
male germ cell	CL:0000015	54.96	gold quality
deltoid	UBERON:0001476	54.30	gold quality
calcaneal tendon	UBERON:0003701	54.12	silver quality
stromal cell of endometrium	CL:0002255	54.10	silver quality
colonic epithelium	UBERON:0000397	54.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	53.93	gold quality
endometrium epithelium	UBERON:0004811	52.86	gold quality
ganglionic eminence	UBERON:0004023	52.70	silver quality
frontal cortex	UBERON:0001870	52.17	gold quality
right frontal lobe	UBERON:0002810	52.08	gold quality
pancreatic ductal cell	CL:0002079	52.07	silver quality
ventricular zone	UBERON:0003053	51.99	gold quality
neocortex	UBERON:0001950	51.83	gold quality
cingulate cortex	UBERON:0003027	51.62	gold quality
ileal mucosa	UBERON:0000331	51.61	silver quality
cortical plate	UBERON:0005343	51.54	silver quality
anterior cingulate cortex	UBERON:0009835	51.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	51.25	gold quality
right coronary artery	UBERON:0001625	51.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	23.82
E-GEOD-135922	yes	13.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting RRH, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385
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-765	99.84	68.24	2442
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-3160-5P	99.28	69.07	1938

Literature-anchored findings (GeneRIF, showing 2)

• Peropsin gene is not a common cause of retinitis pigmentosa or some related retinal degenerations, at least in the set of patients we analyzed. (PMID:17167409)
• By using chimeric mutant peropsins, it was found that peropsin potentially generates an “active form” that drives G-protein signalling in the dark by binding to all-trans-retinal, and that the active form photo-converts to an inactive form containing 11-cis-retinal. (PMID:29476064)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rrh	ENSDARG00000039534
mus_musculus	Rrh	ENSMUSG00000028012
rattus_norvegicus	Rrh	ENSRNOG00000053349
caenorhabditis_elegans		WBGENE00005641
caenorhabditis_elegans		WBGENE00017176

Paralogs (9): OPN3 (ENSG00000054277), OPN1LW (ENSG00000102076), OPN4 (ENSG00000122375), OPN5 (ENSG00000124818), OPN1SW (ENSG00000128617), RHO (ENSG00000163914), OPN1MW2 (ENSG00000166160), OPN1MW (ENSG00000268221), OPN1MW3 (ENSG00000269433)

Protein

Protein identifiers

Visual pigment-like receptor peropsin — O14718 (reviewed: O14718)

All UniProt accessions (2): O14718, A0A494C1B2

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in rpe physiology either by detecting light directly or by monitoring the concentration of retinoids or other photoreceptor-derived compounds.

Subcellular location. Membrane.

Tissue specificity. Found only in the eye, where it is localized to the retinal pigment epithelium (RPE). In the RPE, it is localized to the microvilli that surround the photoreceptor outer segments.

Similarity. Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.

RefSeq proteins (1): NP_006574* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR002962	Peropsin	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR027430	Retinal_BS	Binding_site
IPR050125	GPCR_opsins	Family

Pfam: PF00001

UniProt features (19 total): topological domain 8, transmembrane region 7, chain 1, modified residue 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14718-F1	85.95	0.64

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): 284

Disulfide bonds (1): 98–175

Glycosylation sites (1): 8

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-419771	Opsins

MSigDB gene sets: 95 (showing top): chr4q25, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, MODULE_64, GOBP_PHOTOTRANSDUCTION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_RADIATION, MODULE_123, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, MODULE_113, GOBP_DETECTION_OF_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_RADIATION, GOBP_SENSORY_PERCEPTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), visual perception (GO:0007601), phototransduction (GO:0007602), cellular response to light stimulus (GO:0071482), signal transduction (GO:0007165), detection of visible light (GO:0009584)

GO Molecular Function (4): G protein-coupled receptor activity (GO:0004930), G protein-coupled photoreceptor activity (GO:0008020), protein binding (GO:0005515), photoreceptor activity (GO:0009881)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	2
signal transduction	2
detection of light stimulus	2
sensory perception of light stimulus	1
response to light stimulus	1
cellular response to radiation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
detection of visible light	1
photoreceptor activity	1
binding	1
signaling receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRH	RD3L	P0DJH9	529
RRH	RPE65	Q16518	514
RRH	GPR139	Q6DWJ6	473
RRH	NRL	P54845	455
RRH	RLBP1	P12271	424
RRH	DEXI	O95424	422
RRH	RHAG	Q02094	400
RRH	EFHD1	Q9BUP0	398
RRH	PPP1R42	Q7Z4L9	398
RRH	SLC17A5	Q9NRA2	395
RRH	RFXAP	O00287	383
RRH	LRAT	O95237	355
RRH	MAP6D1	Q9H9H5	354
RRH	RDH5	Q92781	343
RRH	KLK1	P06870	341

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RRH	NSG2	psi-mi:“MI:0915”(physical association)	0.560
RRH	NSG2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): RRH (Two-hybrid)

ESM2 similar proteins: O01668, O02464, O02465, O14718, O15973, O16005, O16017, O16018, O16019, O16020, O18312, O18315, O18481, O18485, O18486, O35214, O96107, P04950, P06002, P08099, P08255, P09241, P17646, P22269, P24603, P28678, P28679, P28680, P29404, P31356, P35356, P35360, P35361, P35362, P87368, P90680, P90745, P91657, Q17053, Q17094

Diamond homologs: O02664, O13227, O14718, O15973, O16005, O35214, O57422, O60431, O77408, O88634, P02699, P02700, P09241, P14416, P21918, P22328, P24603, P28682, P31356, P32309, P32310, P35403, P41590, P41591, P41983, P49912, P51472, P52702, P60026, P61168, P61169, P79756, P79798, P79807, P79809, P79812, P79863, P79902, P79914, Q17094

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

835 predictions. Top by Δscore:

Variant	Effect	Δscore
4:109835361:TTCA:T	acceptor_loss	1.0000
4:109835363:CA:C	acceptor_loss	1.0000
4:109835364:A:AG	acceptor_gain	1.0000
4:109835365:G:GG	acceptor_gain	1.0000
4:109835365:GGTTT:G	acceptor_gain	1.0000
4:109835459:GAC:G	donor_gain	1.0000
4:109835462:G:GG	donor_gain	1.0000
4:109848314:CAAG:C	donor_loss	1.0000
4:109848316:AGGTA:A	donor_loss	1.0000
4:109848317:GGTA:G	donor_loss	1.0000
4:109848318:G:T	donor_loss	1.0000
4:109848319:T:A	donor_loss	1.0000
4:109835365:GGT:G	acceptor_gain	0.9900
4:109835365:GGTT:G	acceptor_gain	0.9900
4:109835460:AC:A	donor_gain	0.9900
4:109836001:TAATA:T	acceptor_loss	0.9900
4:109836003:ATAGG:A	acceptor_loss	0.9900
4:109836004:TA:T	acceptor_loss	0.9900
4:109836005:A:AT	acceptor_loss	0.9900
4:109836006:G:GT	acceptor_loss	0.9900
4:109833044:T:G	donor_gain	0.9800
4:109833298:G:GT	donor_gain	0.9800
4:109835364:AG:A	acceptor_gain	0.9800
4:109835365:GG:G	acceptor_gain	0.9800
4:109835392:T:TA	acceptor_gain	0.9800
4:109835458:TGAC:T	donor_gain	0.9800
4:109835459:GACG:G	donor_gain	0.9800
4:109842463:TTTCA:T	acceptor_loss	0.9800
4:109842464:TTCA:T	acceptor_loss	0.9800
4:109842465:TCAGA:T	acceptor_loss	0.9800

AlphaMissense

2233 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:109833147:A:C	S39R	0.999
4:109833149:T:A	S39R	0.999
4:109833149:T:G	S39R	0.999
4:109833305:G:C	W91C	0.999
4:109833305:G:T	W91C	0.999
4:109836146:G:C	W179C	0.999
4:109836146:G:T	W179C	0.999
4:109842505:T:A	W253R	0.999
4:109842505:T:C	W253R	0.999
4:109833232:T:C	L67P	0.998
4:109833255:A:C	S75R	0.998
4:109833257:T:A	S75R	0.998
4:109833257:T:G	S75R	0.998
4:109833303:T:A	W91R	0.998
4:109833303:T:C	W91R	0.998
4:109835436:G:C	R123P	0.998
4:109836072:T:A	W155R	0.998
4:109836072:T:C	W155R	0.998
4:109836132:T:C	C175R	0.998
4:109836133:G:A	C175Y	0.998
4:109836134:T:G	C175W	0.998
4:109842493:T:C	F249L	0.998
4:109842495:T:A	F249L	0.998
4:109842495:T:G	F249L	0.998
4:109842600:A:C	K284N	0.998
4:109842600:A:T	K284N	0.998
4:109833156:A:C	S42R	0.997
4:109833158:C:A	S42R	0.997
4:109833158:C:G	S42R	0.997
4:109833161:C:A	N43K	0.997

dbSNP variants (sampled 300 via entrez): RS1000019897 (4:109837301 A>G), RS10000762 (4:109826708 C>T), RS1000082528 (4:109844475 A>G,T), RS1000173944 (4:109828198 T>C), RS10007208 (4:109828648 G>A,C,T), RS1000860973 (4:109840133 T>A), RS1000893972 (4:109839784 C>T), RS10008969 (4:109834257 C>G,T), RS1001048397 (4:109833042 T>A), RS1001072520 (4:109839304 T>C), RS1001081526 (4:109826664 G>A,C,T), RS10011949 (4:109842324 A>G), RS1001197199 (4:109838587 A>C), RS1001264070 (4:109831404 C>T), RS1001331961 (4:109832733 A>G)

Disease associations

OMIM: gene MIM:605224 | 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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
trichostatin A	affects expression, decreases reaction	1
tobacco tar	decreases expression, decreases reaction	1
potassium chromate(VI)	affects cotreatment, increases expression	1
diallyl disulfide	decreases expression, decreases reaction	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Nickel	affects expression, decreases reaction	1
Zinc Sulfate	increases expression	1

Clinical trials (associated diseases)

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