IMPG2

Summary

IMPG2 (interphotoreceptor matrix proteoglycan 2, HGNC:18362) is a protein-coding gene on chromosome 3q12.3, encoding Interphotoreceptor matrix proteoglycan 2 (Q9BZV3). Chondroitin sulfate- and hyaluronan-binding proteoglycan involved in the organization of interphotoreceptor matrix; may participate in the maturation and maintenance of the light-sensitive photoreceptor outer segment.

The protein encoded by this gene binds chondroitin sulfate and hyaluronan and is a proteoglycan. The encoded protein plays a role in the organization of the interphotoreceptor matrix and may promote the growth and maintenance of the light-sensitive photoreceptor outer segment. Defects in this gene are a cause of retinitis pigmentosa type 56 and maculopathy, IMPG2-related.

Source: NCBI Gene 50939 — RefSeq curated summary.

At a glance

• Gene–disease (curated): IMPG2-related recessive retinopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,095 total — 77 pathogenic, 50 likely-pathogenic
• Phenotypes (HPO): 53
• MANE Select transcript: NM_016247

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18362
Approved symbol	IMPG2
Name	interphotoreceptor matrix proteoglycan 2
Location	3q12.3
Locus type	gene with protein product
Status	Approved
Aliases	IPM200, RP56, SPACRCAN
Ensembl gene	ENSG00000081148
Ensembl biotype	protein_coding
OMIM	607056
Entrez	50939

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000193391

RefSeq mRNA: 1 — MANE Select: NM_016247 NM_016247

CCDS: CCDS2940

Canonical transcript exons

ENST00000193391 — 19 exons

Exon	Start	End
ENSE00000774747	101242688	101242907
ENSE00000774748	101243529	101244787
ENSE00000774749	101245802	101246105
ENSE00000774753	101269515	101269573
ENSE00000774754	101273581	101273742
ENSE00000774755	101275663	101275745
ENSE00000774756	101276664	101276713
ENSE00000774757	101304146	101304312
ENSE00000934093	101228797	101228876
ENSE00000934094	101229380	101229590
ENSE00000934095	101230957	101231145
ENSE00000934096	101232781	101232991
ENSE00000934097	101253696	101253781
ENSE00000934098	101257529	101257773
ENSE00000934099	101319584	101319832
ENSE00001014439	101267511	101267531
ENSE00001014440	101291479	101291510
ENSE00001077794	101222546	101226981
ENSE00001853323	101320288	101320575

Expression profiles

Bgee: expression breadth broad, 81 present calls, max score 73.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.5776 / max 4277.5506, expressed in 12 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43540	3.2290	11
43542	0.1298	8
43541	0.1105	8
43539	0.1083	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	73.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	70.38	gold quality
pineal body	UBERON:0001905	68.17	silver quality
neuron projection bundle connecting eye with brain	UBERON:0004904	66.66	silver quality
triceps brachii	UBERON:0001509	66.21	gold quality
gluteal muscle	UBERON:0002000	66.10	gold quality
fallopian tube	UBERON:0003889	65.84	gold quality
oviduct epithelium	UBERON:0004804	65.26	silver quality
retina	UBERON:0000966	61.94	silver quality
pigmented layer of retina	UBERON:0001782	61.94	gold quality
buccal mucosa cell	CL:0002336	58.25	gold quality
germinal epithelium of ovary	UBERON:0001304	58.01	silver quality
lower lobe of lung	UBERON:0008949	56.00	silver quality
tibia	UBERON:0000979	55.52	gold quality
lateral globus pallidus	UBERON:0002476	54.45	gold quality
deltoid	UBERON:0001476	53.70	gold quality
bone marrow cell	CL:0002092	53.66	gold quality
choroid plexus epithelium	UBERON:0003911	53.33	silver quality
cortical plate	UBERON:0005343	53.31	gold quality
stromal cell of endometrium	CL:0002255	52.20	silver quality
quadriceps femoris	UBERON:0001377	51.77	gold quality
calcaneal tendon	UBERON:0003701	50.79	silver quality
muscle tissue	UBERON:0002385	50.63	silver quality
skin of hip	UBERON:0001554	50.54	silver quality
lymph node	UBERON:0000029	50.49	gold quality
vastus lateralis	UBERON:0001379	50.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	50.17	silver quality
skeletal muscle tissue	UBERON:0001134	50.03	gold quality
nasal cavity mucosa	UBERON:0001826	50.01	silver quality
cerebellar vermis	UBERON:0004720	49.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	20.61
E-GEOD-137537	yes	15.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting IMPG2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084

Literature-anchored findings (GeneRIF, showing 10)

• IPM 200 represents the second member of a novel family of retinal proteoglycans suspected to be involved in retinal adhesion and photoreceptor cell survival (PMID:10542133)
• identification of IMPG2 mutations in autosomal-recessive retinitis pigmentosa; data show that mutations in a structural component of the interphotoreceptor matrix can cause autosomal-recessive retinitis pigmentosa (PMID:20673862)
• Mutations in IMPG2 cause a severe form of retinitis pigmentosa with symptoms manifesting in the first 2 decades of life. (PMID:24876279)
• IMPG1 and IMPG2 are new causal genes of vitelliform dystrophy, involved in 8% of our families. (PMID:25085631)
• ADULT-ONSET VITELLIFORM MACULAR DYSTROPHY SECONDARY TO A NOVEL IMPG2 GENE VARIANT. (PMID:30300315)
• IMPG2 mutation is associated with retinal dystrophy. (PMID:31264916)
• Upon disruption of the myosin-tail homology domain, inner segment plasma membrane proteins, including syntaxin 3 (STX3), synaptosome-associated protein 25 (SNAP25), and interphotoreceptor matrix proteoglycan 2 (IMPG2), rapidly accumulated in the outer segment. (PMID:31694913)
• Whole exome sequencing identifies a novel splice-site mutation in IMPG2 gene causing Stargardt-like juvenile macular dystrophy in a north Indian family. (PMID:34990796)
• Identification of a Complex Allele in IMPG2 as a Cause of Adult-Onset Vitelliform Macular Dystrophy. (PMID:35608844)
• IMPG2-Related Maculopathy. (PMID:37806544)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	impg2a	ENSDARG00000019782
danio_rerio	impg2b	ENSDARG00000100105
danio_rerio	impg2b	ENSDARG00000100288
mus_musculus	Impg2	ENSMUSG00000035270
rattus_norvegicus	Senp7	ENSRNOG00000001616

Paralogs (1): IMPG1 (ENSG00000112706)

Protein

Protein identifiers

Interphotoreceptor matrix proteoglycan 2 — Q9BZV3 (reviewed: Q9BZV3)

Alternative names: Interphotoreceptor matrix proteoglycan of 200 kDa, Sialoprotein associated with cones and rods proteoglycan

All UniProt accessions (2): Q9BZV3, F1T0J3

UniProt curated annotations — full annotation on UniProt →

Function. Chondroitin sulfate- and hyaluronan-binding proteoglycan involved in the organization of interphotoreceptor matrix; may participate in the maturation and maintenance of the light-sensitive photoreceptor outer segment. Binds heparin.

Subcellular location. Photoreceptor outer segment membrane. Photoreceptor inner segment membrane. Secreted. Extracellular space. Extracellular matrix. Interphotoreceptor matrix.

Tissue specificity. Expressed in the retina (at protein level). Expressed by photoreceptors of the interphotoreceptor matrix (IPM) surrounding both rods and cones (at protein level). IPM occupies the subretinal space between the apices of the retinal pigment epithelium and the neural retina. Expressed in the pineal gland (at protein level).

Post-translational modifications. Highly glycosylated (N- and O-linked carbohydrates).

Disease relevance. Retinitis pigmentosa 56 (RP56) [MIM:613581] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry. Macular dystrophy, vitelliform, 5 (VMD5) [MIM:616152] A form of macular dystrophy, a retinal disease in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea. Vitelliform macular dystrophies are characterized by yellow, lipofuscin-containing deposits, usually localized at the center of the macula. VMD5 features include late-onset moderate visual impairment and preservation of retinal pigment epithelium reflectivity. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_057331* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR000742	EGF	Domain
IPR036364	SEA_dom_sf	Homologous_superfamily
IPR039861	IMPG	Family

Pfam: PF01390

UniProt features (60 total): sequence variant 21, glycosylation site 10, region of interest 7, disulfide bond 6, sequence conflict 5, domain 4, compositionally biased region 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZV3-F1	54.28	0.12

Functional residue map

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

Disulfide bonds (6): 1014–1025, 1019–1036, 1038–1050, 1054–1067, 1061–1077, 1079–1092

Glycosylation sites (10): 154, 190, 192, 301, 320, 370, 544, 556, 942, 956

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): CHX10_01, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_SENSORY_PERCEPTION, KANG_IMMORTALIZED_BY_TERT_DN, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS, GOMF_HEPARIN_BINDING, GOBP_RETINA_DEVELOPMENT_IN_CAMERA_TYPE_EYE, GOBP_CAMERA_TYPE_EYE_MORPHOGENESIS, GOBP_RETINA_MORPHOGENESIS_IN_CAMERA_TYPE_EYE, GOBP_EYE_MORPHOGENESIS, TAATTA_CHX10_01

GO Biological Process (4): visual perception (GO:0007601), intracellular protein localization (GO:0008104), extracellular matrix organization (GO:0030198), retina morphogenesis in camera-type eye (GO:0060042)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), hyaluronic acid binding (GO:0005540), heparin binding (GO:0008201)

GO Cellular Component (7): extracellular matrix (GO:0031012), interphotoreceptor matrix (GO:0033165), signaling receptor complex (GO:0043235), extracellular region (GO:0005576), membrane (GO:0016020), cell projection (GO:0042995), cell periphery (GO:0071944)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
sensory perception of light stimulus	1
macromolecule localization	1
extracellular structure organization	1
external encapsulating structure organization	1
anatomical structure morphogenesis	1
camera-type eye morphogenesis	1
retina development in camera-type eye	1
structural molecule activity	1
extracellular matrix	1
carboxylic acid binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
external encapsulating structure	1
specialized extracellular matrix	1
protein-containing complex	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IMPG2	EYS	Q5T1H1	853
IMPG2	PCARE	A6NGG8	840
IMPG2	PRCD	Q00LT1	819
IMPG2	ZNF513	Q8N8E2	807
IMPG2	CERKL	Q49MI3	787
IMPG2	PDE6A	P16499	779
IMPG2	BEST1	O76090	775
IMPG2	PDE6G	P18545	775
IMPG2	RDH12	Q96NR8	774
IMPG2	PRPH2	P23942	772
IMPG2	CNGB1	Q14028	772
IMPG2	TULP1	O00294	747
IMPG2	FSCN2	O14926	745
IMPG2	NR2E3	Q9Y5X4	742
IMPG2	ABCA4	P78363	741

IntAct

0 interactions, top by confidence:

BioGRID (8): IMPG2 (Cross-Linking-MS (XL-MS)), IMPG2 (Affinity Capture-MS), IMPG2 (Proximity Label-MS), IMPG2 (Proximity Label-MS), IMPG2 (Proximity Label-MS), IMPG2 (Proximity Label-MS), IMPG2 (Proximity Label-MS), IMPG2 (Proximity Label-MS)

ESM2 similar proteins: A0A1B0GV85, A1KXC4, A6QLF8, B1ARY8, O14594, O35188, O55145, O60279, O60667, O95196, P07141, P09603, P40225, P40226, P42705, P55066, P55067, P70628, P78423, Q149B8, Q17R60, Q28645, Q2LA85, Q2TB54, Q3TNW5, Q52S86, Q58Y74, Q5IS41, Q5M871, Q5R770, Q5T2D2, Q6PIX9, Q6UXF1, Q6ZVL6, Q7Z434, Q80XH2, Q8BHE4, Q8BT18, Q8C0D9, Q8CAE9

Diamond homologs: O95196, P70628, Q1XI86, Q71M36, Q80XH2, Q8JIR8, Q9BZV3, Q9DF69, Q9ERQ6, Q17R60, Q8R1W8, Q9ET62, Q9GMS5, A0A0C5PRQ1, A0FKN6, A8Q2D1, B3EWZ5, B3EWZ6, D2KBH9, D5FM34, D5FM37, D5FM38, K7Z9Q9, O16977, O17264, O43897, O57382, O57460, O62243, P07584, P0DJJ2, P0DM61, P0DM62, P13497, P25723, P28825, P28826, P31579, P31580, P31581

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1095 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	77
Likely pathogenic	50
Uncertain significance	600
Likely benign	262
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065646	NM_016247.4(IMPG2):c.2233del (p.Glu745fs)	Pathogenic
1069110	NM_016247.4(IMPG2):c.2038del (p.Glu680fs)	Pathogenic
1069770	NM_016247.4(IMPG2):c.224G>A (p.Trp75Ter)	Pathogenic
1074499	NM_016247.4(IMPG2):c.3448del (p.Leu1150fs)	Pathogenic
1075431	NM_016247.4(IMPG2):c.3159_3160del (p.Leu1053_Cys1054insTer)	Pathogenic
1076829	NM_016247.4(IMPG2):c.1350G>A (p.Trp450Ter)	Pathogenic
1213852	NM_016247.4(IMPG2):c.2566C>T (p.Gln856Ter)	Pathogenic
1213854	NM_016247.4(IMPG2):c.3405_3408del (p.Glu1137fs)	Pathogenic
1371852	NM_016247.4(IMPG2):c.3093_3097dup (p.Glu1033fs)	Pathogenic
1406029	NM_016247.4(IMPG2):c.255dup (p.Pro86fs)	Pathogenic
1440615	NM_016247.4(IMPG2):c.1100dup (p.Leu367fs)	Pathogenic
1454009	NC_000003.11:g.(?100986335)(100986395_?)del	Pathogenic
1454130	NM_016247.4(IMPG2):c.2269dup (p.Glu757fs)	Pathogenic
1455690	NC_000003.11:g.(?101010303)(101010374_?)del	Pathogenic
1458492	NM_016247.4(IMPG2):c.3169C>T (p.Gln1057Ter)	Pathogenic
191181	NM_016247.4(IMPG2):c.513T>G (p.Tyr171Ter)	Pathogenic
1950590	NM_016247.4(IMPG2):c.263del (p.Gly88fs)	Pathogenic
2007525	NM_016247.4(IMPG2):c.216_217del (p.Arg73fs)	Pathogenic
2019860	NM_016247.4(IMPG2):c.2481del (p.Glu828fs)	Pathogenic
2022831	NM_016247.4(IMPG2):c.3535C>T (p.Gln1179Ter)	Pathogenic
2027768	NM_016247.4(IMPG2):c.3147del (p.Cys1050fs)	Pathogenic
2035063	NM_016247.4(IMPG2):c.1543G>T (p.Gly515Ter)	Pathogenic
2097907	NM_016247.4(IMPG2):c.1483C>T (p.Gln495Ter)	Pathogenic
2098104	NM_016247.4(IMPG2):c.2560C>T (p.Gln854Ter)	Pathogenic
2099126	NM_016247.4(IMPG2):c.1071T>A (p.Tyr357Ter)	Pathogenic
2105946	NM_016247.4(IMPG2):c.2839C>T (p.Gln947Ter)	Pathogenic
2118068	NM_016247.4(IMPG2):c.3126C>A (p.Tyr1042Ter)	Pathogenic
2119365	NM_016247.4(IMPG2):c.1100del (p.Leu367fs)	Pathogenic
236459	NM_016247.4(IMPG2):c.2412_2413del (p.Ser804_Ala805insTer)	Pathogenic
236460	NM_016247.4(IMPG2):c.68dup (p.Asp23fs)	Pathogenic

SpliceAI

2864 predictions. Top by Δscore:

Variant	Effect	Δscore
3:101228795:A:AC	donor_gain	1.0000
3:101228796:C:CC	donor_gain	1.0000
3:101228796:CA:C	donor_gain	1.0000
3:101229395:A:AC	donor_gain	1.0000
3:101229396:C:CC	donor_gain	1.0000
3:101229396:CTG:C	donor_gain	1.0000
3:101229396:CTGCT:C	donor_gain	1.0000
3:101229407:CAT:C	donor_gain	1.0000
3:101229591:C:CC	acceptor_gain	1.0000
3:101232776:CATA:C	donor_loss	1.0000
3:101232777:ATACC:A	donor_loss	1.0000
3:101232778:TA:T	donor_loss	1.0000
3:101232819:T:A	donor_gain	1.0000
3:101242682:TCATA:T	donor_loss	1.0000
3:101242683:CATA:C	donor_loss	1.0000
3:101242684:ATACC:A	donor_loss	1.0000
3:101242685:TA:T	donor_loss	1.0000
3:101242686:A:C	donor_loss	1.0000
3:101242687:C:CA	donor_loss	1.0000
3:101242904:CCAG:C	acceptor_gain	1.0000
3:101242905:CAG:C	acceptor_gain	1.0000
3:101242905:CAGC:C	acceptor_gain	1.0000
3:101242908:C:CC	acceptor_gain	1.0000
3:101242908:CTA:C	acceptor_loss	1.0000
3:101242909:T:C	acceptor_loss	1.0000
3:101253690:ACAT:A	donor_loss	1.0000
3:101253691:CATA:C	donor_loss	1.0000
3:101253692:ATACC:A	donor_loss	1.0000
3:101253693:TA:T	donor_loss	1.0000
3:101253694:A:AC	donor_gain	1.0000

AlphaMissense

8185 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:101232941:A:G	C1025R	0.999
3:101232967:A:C	F1016C	0.999
3:101242819:C:G	R964P	0.999
3:101242821:A:C	S963R	0.999
3:101242821:A:T	S963R	0.999
3:101242823:T:G	S963R	0.999
3:101242849:A:G	F954S	0.999
3:101242894:A:G	L939P	0.999
3:101232814:C:G	C1067S	0.998
3:101232815:A:T	C1067S	0.998
3:101232939:A:C	C1025W	0.998
3:101232940:C:G	C1025S	0.998
3:101232941:A:T	C1025S	0.998
3:101232958:C:T	C1019Y	0.998
3:101232959:A:G	C1019R	0.998
3:101232966:A:C	F1016L	0.998
3:101232966:A:T	F1016L	0.998
3:101232968:A:G	F1016L	0.998
3:101243596:A:C	F912C	0.998
3:101243617:A:G	L905P	0.998
3:101232815:A:G	C1067R	0.997
3:101232831:G:C	C1061W	0.997
3:101232832:C:G	C1061S	0.997
3:101232833:A:T	C1061S	0.997
3:101232853:C:G	C1054S	0.997
3:101232854:A:T	C1054S	0.997
3:101232866:A:G	C1050R	0.997
3:101232900:G:C	C1038W	0.997
3:101232902:A:G	C1038R	0.997
3:101232907:C:G	C1036S	0.997

dbSNP variants (sampled 300 via entrez): RS1000016014 (3:101316577 G>A,T), RS1000038042 (3:101281076 A>G), RS1000084903 (3:101251162 T>C), RS1000086216 (3:101231707 G>C), RS1000096361 (3:101301993 T>C), RS1000154426 (3:101231970 A>G), RS1000182627 (3:101298062 T>C), RS1000204657 (3:101320484 T>C), RS1000284072 (3:101273262 T>C), RS1000328594 (3:101288135 C>T), RS1000343437 (3:101237907 G>A,C), RS1000421307 (3:101313784 G>A,T), RS1000439351 (3:101311555 T>A), RS1000459991 (3:101231268 A>C), RS1000473970 (3:101306940 A>T)

Disease associations

OMIM: gene MIM:607056 | disease phenotypes: MIM:616152, MIM:613581, MIM:209900, MIM:268000, MIM:120970, MIM:608161, MIM:153700

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 56	Definitive	Autosomal recessive
vitelliform macular dystrophy 5	Definitive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant
adult-onset foveomacular vitelliform dystrophy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
IMPG2-related recessive retinopathy	Definitive	AR

Mondo (11): inherited retinal dystrophy (MONDO:0019118), vitelliform macular dystrophy 5 (MONDO:0014509), retinitis pigmentosa 56 (MONDO:0013314), Bardet-Biedl syndrome (MONDO:0015229), retinitis pigmentosa (MONDO:0019200), prostate cancer (MONDO:0008315), IMPG2-related recessive retinopathy (MONDO:0700241), cone-rod dystrophy (MONDO:0015993), vitelliform macular dystrophy 3 (MONDO:0024561), vitelliform macular dystrophy 2 (MONDO:0007931), adult-onset foveomacular vitelliform dystrophy (MONDO:0011979)

Orphanet (7): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Adult-onset foveomacular vitelliform dystrophy (Orphanet:99000), Retinitis pigmentosa (Orphanet:791), Bardet-Biedl syndrome (Orphanet:110), Familial prostate cancer (Orphanet:1331), Cone rod dystrophy (Orphanet:1872), Best vitelliform macular dystrophy (Orphanet:1243)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000478	Abnormality of the eye
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001123	Visual field defect
HP:0001139	Chorioretinal scalloped atrophy
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0007663	Reduced visual acuity

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004131_6	Inflammatory bowel disease	3.000000e-08
GCST004132_78	Crohn’s disease	4.000000e-07
GCST90002390_154	Mean corpuscular hemoglobin	8.000000e-16
GCST90002392_195	Mean corpuscular volume	1.000000e-14
GCST90020026_218	Hip index	4.000000e-08
GCST90020026_220	Hip index	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Oxygen	increases expression	1
Silicon Dioxide	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy