RP1L1

Summary

RP1L1 (RP1 like 1, HGNC:15946) is a protein-coding gene on chromosome 8p23.1, encoding Retinitis pigmentosa 1-like 1 protein (Q8IWN7). Required for the differentiation of photoreceptor cells.

This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD).

Source: NCBI Gene 94137 — RefSeq curated summary.

At a glance

• Gene–disease (curated): occult macular dystrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 60
• Clinical variants (ClinVar): 1,752 total — 11 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_178857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15946
Approved symbol	RP1L1
Name	RP1 like 1
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	DCDC4B
Ensembl gene	ENSG00000183638
Ensembl biotype	protein_coding
OMIM	608581
Entrez	94137

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000329335, ENST00000382483

RefSeq mRNA: 1 — MANE Select: NM_178857 NM_178857

CCDS: CCDS43708

Canonical transcript exons

ENST00000382483 — 4 exons

Exon	Start	End
ENSE00001333313	10654898	10655143
ENSE00001492246	10606349	10613346
ENSE00001492248	10616446	10616587
ENSE00003640044	10622593	10623220

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 60.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1772 / max 84.0942, expressed in 9 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91808	0.1083	9
91809	0.0438	7
91807	0.0184	5
91810	0.0068	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	60.12	silver quality
buccal mucosa cell	CL:0002336	57.66	gold quality
bone marrow cell	CL:0002092	57.65	silver quality
colonic epithelium	UBERON:0000397	52.27	gold quality
tendon of biceps brachii	UBERON:0008188	51.26	gold quality
pigmented layer of retina	UBERON:0001782	47.88	silver quality
skin of leg	UBERON:0001511	46.61	gold quality
ventricular zone	UBERON:0003053	46.52	gold quality
bone marrow	UBERON:0002371	46.25	gold quality
ganglionic eminence	UBERON:0004023	45.24	gold quality
zone of skin	UBERON:0000014	45.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	45.17	gold quality
skin of abdomen	UBERON:0001416	44.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	44.66	silver quality
skeletal muscle tissue	UBERON:0001134	44.44	gold quality
muscle tissue	UBERON:0002385	44.08	gold quality
apex of heart	UBERON:0002098	44.07	silver quality
lower esophagus mucosa	UBERON:0035834	44.05	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
uterine cervix	UBERON:0000002	43.31	silver quality
islet of Langerhans	UBERON:0000006	43.04	silver quality
monocyte	CL:0000576	43.00	gold quality
vagina	UBERON:0000996	42.85	gold quality
ectocervix	UBERON:0012249	42.79	gold quality
leukocyte	CL:0000738	42.75	gold quality
duodenum	UBERON:0002114	42.61	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
nasal cavity mucosa	UBERON:0001826	42.57	gold quality
tendon	UBERON:0000043	42.15	gold quality
placenta	UBERON:0001987	41.57	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting RP1L1, 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-3925-3P	100.00	69.95	1237
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378F	98.43	65.66	554

Literature-anchored findings (GeneRIF, showing 21)

• The RP1L1 gene encodes a large, highly polymorphic, retinal-specific protein. No RP1L1 disease-causing mutations were identified in any of the samples tested. (PMID:12724644)
• Amino acid substitution of p.Arg45Trp in retinitis pigmentosa 1-like 1 (RP1L1) was found in three occult macular dystrophy (OMD)families and p.Trp960Arg in a remaining OMD family. (PMID:20826268)
• The abnormalities in the multifocal electroretinograms and optical coherence tomography observed in the occult macular dystrophy patients of different durations strongly support the contribution of RP1L1 mutation to the presence of this disease. (PMID:22466457)
• The clinical phenotypes differed between the proband and her mother and were indistinguishable from other sporadic or RP1L1-unassociated OMD patients, suggesting that mutation-dependent clinical features may not be present. (PMID:22504327)
• Occult macular dystrophy is a genetically heterogeneous disorder in a white family of European descent, screened for genetic mutations in the RP1L1 gene. (PMID:23229695)
• RP1L1 mutations are associated with retinal diseases, including retinitis pigmentosa and occult macular dystrophy. (PMID:23281133)
• These findings indicate that the phenotype in some cases of occult macular dystrophy with an Arg45Trp mutation in the RP1L1 gene can be unilateral for a considerable period. (PMID:23619761)
• Our study revealed that the previously identified mutation in the retinitis pigmentosa 1L1 gene from Japanese families, R45W3, also was found in Korean occult macular degeneration patients. (PMID:23745001)
• We describe in detail a case of bilateral chronic subfoveal serous retinal detachment in an atypical occult macular dystrophy patient carrying a novel heterozygous RP1L1 mutation (p.S1199P) (PMID:24838559)
• findings indicate that a homozygous p.S1210P exchange in the RP1L1 gene can cause cone dystrophy (PMID:25692141)
• A p.Arg45Trp mutation in the RP1L1 gene was identified in the Occult macular dystrophy patient, in the two symptomatic offspring and also in two of the asymptomatic siblings of the patient. (PMID:26782618)
• We propose that the combination of heterozygous loss-of-function mutations in these genes drives syndromic retinal dystrophy, likely through the genetic interaction of at least two loci. (PMID:27029556)
• A unique motif including six amino acids (1196-1201) downstream of the doublecortin domain could be a hot spot for RP1L1 pathogenic variants. The significant association of the morphologic phenotypes and genotypes indicates that there are two types of pathophysiology underlying the occult macular dysfunction syndrome (PMID:27623337)
• the presence of pathogenic RP1L1 variants is significantly associated with characteristic abnormalities of the photoreceptor layer in the macular region (e.g., blurring of the ellipsoid zone [EZ] and absence of the interdigitation zone (PMID:29196766)
• Autosomal dominant occult macular dystrophy (OCMD) phenotype showed consistent clinical findings including classical microstructural changes on SD-OCT. An important hallmark of RP1L1-related OCMD is the dominant family history with reduced penetrance. (PMID:30025130)
• Homozygous loss-of-function mutations in RP1L1 gene is associated with retinitis pigmentosa. (PMID:31833436)
• Two recurrent RP1L1 variants are related to occult macular dystrophy in the Chinese population. (PMID:32176261)
• A variant in the RP1L1 gene in a family with occult macular dystrophy in a predicted intrinsically disordered region. (PMID:32940107)
• RP1L1 rs3924612 gene polymorphism and RP1L1 protein associations among patients with early age-related macular degeneration. (PMID:34865606)
• Distinct Clinical Effects of Two RP1L1 Hotspots in East Asian Patients With Occult Macular Dystrophy (Miyake Disease): EAOMD Report 4. (PMID:38265784)
• Research progress of RP1L1 gene in disease. (PMID:38485037)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rp1l1b	ENSDARG00000088377
danio_rerio	rp1l1a	ENSDARG00000089458
mus_musculus	Rp1l1	ENSMUSG00000046049
rattus_norvegicus	Rp1l1	ENSRNOG00000046326
caenorhabditis_elegans	F27C1.11	WBGENE00017858
caenorhabditis_elegans	F27C1.13	WBGENE00017860

Paralogs (1): RP1 (ENSG00000104237)

Protein

Protein identifiers

Retinitis pigmentosa 1-like 1 protein — Q8IWN7 (reviewed: Q8IWN7)

All UniProt accessions (1): Q8IWN7

UniProt curated annotations — full annotation on UniProt →

Function. Required for the differentiation of photoreceptor cells. Plays a role in the organization of outer segment of rod and cone photoreceptors.

Subunit / interactions. Interacts with RP1; has a synergistic effect with RP1 in photoreceptor differentiation.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Cell projection. Cilium. Photoreceptor outer segment.

Tissue specificity. Retinal-specific; expressed in photoreceptor.

Disease relevance. Occult macular dystrophy (OCMD) [MIM:613587] An inherited macular dystrophy characterized by progressive loss of macular function but normal ophthalmoscopic appearance. It is typically characterized by a central cone dysfunction leading to a loss of vision despite normal ophthalmoscopic appearance, normal fluorescein angiography, and normal full-field electroretinogram (ERGs), but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly reduced at the central retina. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 88 (RP88) [MIM:618826] A form of retinitis pigmentosa, 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. RP88 is an autosomal recessive form. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal part contains a large repetitive region which contains an unusually high percentage of glutamine, glycine and above all glutamic acid residues.

Polymorphism. The exact length of RP1L1 is variable between individuals due to the presence of several length polymorphisms. The sequence shown here is that of allele RP1L1-1 and includes 3 repeats (from aa 1292-1342) with a length of 16 amino acids. The number of repeats is highly polymorphic and varies among different alleles, ranging from 3 to 8.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWN7-1	1	yes
Q8IWN7-2	2

RefSeq proteins (1): NP_849188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003533	Doublecortin_dom	Domain
IPR036572	Doublecortin_dom_sf	Homologous_superfamily

Pfam: PF03607

UniProt features (128 total): sequence variant 53, compositionally biased region 32, repeat 28, region of interest 8, domain 2, coiled-coil region 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWN7-F1	38.97	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, CHX10_01, FREAC3_01, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_CILIUM_ORGANIZATION, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_SENSORY_PERCEPTION, GOCC_NEURON_PROJECTION, GOBP_SENSORY_ORGAN_DEVELOPMENT

GO Biological Process (8): visual perception (GO:0007601), axoneme assembly (GO:0035082), intracellular signal transduction (GO:0035556), photoreceptor cell outer segment organization (GO:0035845), photoreceptor cell development (GO:0042461), photoreceptor cell maintenance (GO:0045494), retina development in camera-type eye (GO:0060041), cell projection organization (GO:0030030)

GO Molecular Function (0):

GO Cellular Component (8): photoreceptor outer segment (GO:0001750), microtubule (GO:0005874), axoneme (GO:0005930), photoreceptor connecting cilium (GO:0032391), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	2
cellular component organization	2
photoreceptor cell cilium	2
sensory perception of light stimulus	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
signal transduction	1
photoreceptor cell development	1
photoreceptor cell differentiation	1
neuron development	1
retina homeostasis	1
multicellular organismal process	1
camera-type eye development	1
anatomical structure development	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
ciliary transition zone	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

999 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RP1L1	MSRA	Q9UJ68	943
RP1L1	SOX7	Q9BT81	858
RP1L1	CFAP418	Q96NL8	661
RP1L1	EYS	Q5T1H1	631
RP1L1	PRPH2	P23942	611
RP1L1	PCARE	A6NGG8	610
RP1L1	ABCA4	P78363	587
RP1L1	RPGR	Q92834	583
RP1L1	REEP6	Q96HR9	577
RP1L1	USH2A	O75445	576
RP1L1	ROM1	Q03395	575
RP1L1	TTC8	Q8TAM2	570
RP1L1	FAM161A	Q3B820	527
RP1L1	CERKL	Q49MI3	522
RP1L1	NR2E3	Q9Y5X4	521

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RP1L1	ARL3	psi-mi:“MI:0407”(direct interaction)	0.440
RP1L1	FYN	psi-mi:“MI:0915”(physical association)	0.400
RP1L1	GRB2	psi-mi:“MI:0915”(physical association)	0.400
NCK1	RP1L1	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0A096LP49, A0A8V8TNH8, A0A8V8TPE2, A2VE02, A5D7I0, A6NDY2, A6NGG8, A6NIJ5, A6NNJ1, A8MXJ8, A8MYA2, B1ASB6, B2RW88, D6RGX4, O60269, P0C7V4, P0C7W8, P0C7W9, P0C7X0, P0DV75, P0DV76, Q2KIS6, Q2NL68, Q3SY00, Q4R736, Q4V8B5, Q5RCQ2, Q5SZB4, Q5VZ46, Q5XIK6, Q658T7, Q66JV7, Q6NS69, Q6PAC4, Q6ZMY3, Q76N32, Q7TSA6, Q7Z591, Q80VW7, Q80X53

Diamond homologs: A2VCK2, A8MYV0, D3ZR10, P56715, P56716, Q550F6, Q5DU00, Q69Z08, Q8CGM2, Q8IWN7, Q8MJ03, Q8MJ04, Q8MJ05, Q8MJ06, Q9D1B8, Q9UHG0, D2I3C6, O15075, O43602, O88809, Q5MPA9, Q6PGN3, Q8N568, Q95QC4, Q9ESI7, Q9JLM8, Q9VUI3, B3NKK1, Q7PLI7, B4GXC2, B4IMC3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1752 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	35
Uncertain significance	1115
Likely benign	241
Benign	142

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065635	NM_178857.6(RP1L1):c.6530T>G (p.Leu2177Ter)	Pathogenic
1213905	NM_178857.6(RP1L1):c.2464C>T (p.Arg822Ter)	Pathogenic
3250002	NC_000008.11:g.(10616588_10622592)(10623202?)del	Pathogenic
3250003	NC_000008.11:g.(?10606894)(10623202_?)del	Pathogenic
3765542	NM_178857.6(RP1L1):c.2116G>T (p.Gly706Ter)	Pathogenic
50376	NM_178857.6(RP1L1):c.603del (p.Lys203fs)	Pathogenic
828062	NM_178857.6(RP1L1):c.5470C>T (p.Gln1824Ter)	Pathogenic
828063	NM_178857.6(RP1L1):c.56C>A (p.Pro19His)	Pathogenic
828064	NM_178857.6(RP1L1):c.3955_3956insGGACTAAAGTAATAGAAGGGCTGCAAGAAGAGAGGGTGCAGTTAGAGG (p.Glu1318_Ala1319insGlyThrLysValIleGluGlyLeuGlnGluGluArgValGlnLeuGlu)	Pathogenic
987300	NM_178857.6(RP1L1):c.1122G>A (p.Trp374Ter)	Pathogenic
996800	NM_178857.6(RP1L1):c.2107C>T (p.Arg703Ter)	Pathogenic
1048138	NM_178857.6(RP1L1):c.1024_1026delinsCTCCT (p.Arg342fs)	Likely pathogenic
1048147	NM_178857.6(RP1L1):c.196G>C (p.Asp66His)	Likely pathogenic
1325012	NM_178857.6(RP1L1):c.3509C>A (p.Ser1170Ter)	Likely pathogenic
1335944	NM_178857.6(RP1L1):c.3925G>T (p.Gly1309Ter)	Likely pathogenic
1678613	NM_178857.6(RP1L1):c.2380G>T (p.Glu794Ter)	Likely pathogenic
1879704	NM_178857.6(RP1L1):c.6124C>T (p.Gln2042Ter)	Likely pathogenic
2432977	NM_178857.6(RP1L1):c.4403dup (p.Ser1469fs)	Likely pathogenic
2432983	NM_178857.6(RP1L1):c.2077C>T (p.Arg693Ter)	Likely pathogenic
2629381	NM_178857.6(RP1L1):c.1215T>G (p.Tyr405Ter)	Likely pathogenic
2633017	NM_178857.6(RP1L1):c.796_797insTT (p.Ser266fs)	Likely pathogenic
3027964	NM_178857.6(RP1L1):c.5438A>G (p.Asn1813Ser)	Likely pathogenic
3027971	NM_178857.6(RP1L1):c.5154G>C (p.Thr1718=)	Likely pathogenic
3027989	NM_178857.6(RP1L1):c.4483C>T (p.Pro1495Ser)	Likely pathogenic
3028015	NM_178857.6(RP1L1):c.3026_3029del (p.Ala1009fs)	Likely pathogenic
3028037	NM_178857.6(RP1L1):c.1779G>T (p.Thr593=)	Likely pathogenic
3028049	NM_178857.6(RP1L1):c.1288C>T (p.Gln430Ter)	Likely pathogenic
3028060	NM_178857.6(RP1L1):c.583C>T (p.Gln195Ter)	Likely pathogenic
3028065	NM_178857.6(RP1L1):c.397G>T (p.Glu133Ter)	Likely pathogenic
3249352	NM_178857.6(RP1L1):c.5540_5541del (p.Glu1847fs)	Likely pathogenic

SpliceAI

2028 predictions. Top by Δscore:

Variant	Effect	Δscore
8:10616442:TCAC:T	donor_loss	1.0000
8:10616443:CACCG:C	donor_loss	1.0000
8:10616444:A:AC	donor_gain	1.0000
8:10616444:ACCGT:A	donor_loss	1.0000
8:10616445:C:A	donor_loss	1.0000
8:10616445:C:CC	donor_gain	1.0000
8:10622588:CCTA:C	donor_loss	1.0000
8:10622589:CTACC:C	donor_loss	1.0000
8:10622590:TA:T	donor_loss	1.0000
8:10623218:CCG:C	acceptor_gain	1.0000
8:10623219:CG:C	acceptor_gain	1.0000
8:10623219:CGC:C	acceptor_gain	1.0000
8:10623221:C:CC	acceptor_gain	1.0000
8:10674800:TGGTC:T	donor_gain	1.0000
8:10698003:CAGGT:C	donor_loss	1.0000
8:10698004:AGGTG:A	donor_loss	1.0000
8:10698005:GGTGA:G	donor_loss	1.0000
8:10698006:GTG:G	donor_loss	1.0000
8:10700231:CCAG:C	acceptor_loss	1.0000
8:10700234:GGA:G	acceptor_gain	1.0000
8:10613016:T:TA	donor_gain	0.9900
8:10613034:T:TA	donor_gain	0.9900
8:10613035:C:A	donor_gain	0.9900
8:10613071:T:TA	donor_gain	0.9900
8:10613353:CGCAG:C	acceptor_gain	0.9900
8:10613356:A:T	acceptor_gain	0.9900
8:10613357:G:C	acceptor_gain	0.9900
8:10616444:AC:A	donor_gain	0.9900
8:10616445:CC:C	donor_gain	0.9900
8:10616445:CCG:C	donor_gain	0.9900

AlphaMissense

15488 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:10622960:A:T	V81D	0.996
8:10623089:A:G	F38S	0.996
8:10622974:A:C	F76L	0.993
8:10622974:A:T	F76L	0.993
8:10622976:A:G	F76L	0.993
8:10623064:A:C	F46L	0.993
8:10623064:A:T	F46L	0.993
8:10623066:A:G	F46L	0.993
8:10623088:G:C	F38L	0.993
8:10623088:G:T	F38L	0.993
8:10623090:A:G	F38L	0.993
8:10623028:A:C	F58L	0.991
8:10623028:A:T	F58L	0.991
8:10623030:A:G	F58L	0.991
8:10611220:A:G	W960R	0.987
8:10611220:A:T	W960R	0.987
8:10622898:A:C	Y102D	0.986
8:10622999:A:T	L68H	0.985
8:10623089:A:C	F38C	0.985
8:10622629:A:C	F191L	0.984
8:10622629:A:T	F191L	0.984
8:10622631:A:G	F191L	0.984
8:10623044:A:T	V53D	0.983
8:10622999:A:G	L68P	0.982
8:10623082:C:A	K40N	0.982
8:10623082:C:G	K40N	0.982
8:10623011:A:T	L64H	0.981
8:10622660:A:G	F181S	0.980
8:10622648:G:T	A185D	0.978
8:10623011:A:G	L64P	0.978

dbSNP variants (sampled 300 via entrez): RS1000017767 (8:10614236 T>A), RS1000044667 (8:10629469 G>A,C), RS1000080253 (8:10606643 C>T), RS1000100213 (8:10655300 G>C), RS1000161761 (8:10630401 G>C,T), RS1000170827 (8:10619892 C>G), RS1000185788 (8:10621200 G>A,C), RS1000212411 (8:10643340 GA>G,GAA), RS1000233374 (8:10649995 A>G), RS1000249218 (8:10646072 T>C), RS1000326497 (8:10616185 A>C), RS1000340889 (8:10640660 T>G), RS1000350764 (8:10623896 T>G), RS1000386724 (8:10653478 ATACACACACACACACG>A), RS1000403162 (8:10624112 T>C,G)

Disease associations

OMIM: gene MIM:608581 | disease phenotypes: MIM:618826, MIM:613587, MIM:268000, MIM:608571, MIM:120970, MIM:248200, MIM:616487

GenCC curated gene-disease

Disease	Classification	Inheritance
occult macular dystrophy	Definitive	Autosomal dominant
retinitis pigmentosa	Definitive	Autosomal recessive
retinitis pigmentosa 88	Strong	Autosomal recessive
cone dystrophy	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
occult macular dystrophy	Definitive	AD

Mondo (13): retinitis pigmentosa 88 (MONDO:0032940), inherited retinal dystrophy (MONDO:0019118), occult macular dystrophy (MONDO:0013316), congenital portosystemic shunt (MONDO:0018811), retinitis pigmentosa (MONDO:0019200), optic atrophy (MONDO:0003608), ulnar/fibula ray defect-brachydactyly syndrome (MONDO:0012063), cone-rod dystrophy (MONDO:0015993), intellectual disability (MONDO:0001071), retinal disorder (MONDO:0005283), Stargardt disease (MONDO:0019353), epidermolysis bullosa simplex with nail dystrophy (MONDO:0014661), cone dystrophy (MONDO:0000455)

Orphanet (8): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Occult macular dystrophy (Orphanet:247834), Congenital portosystemic shunt (Orphanet:480531), Retinitis pigmentosa (Orphanet:791), Ulnar/fibula ray defect-brachydactyly syndrome (Orphanet:52056), Cone rod dystrophy (Orphanet:1872), Stargardt disease (Orphanet:827), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

44 total (30 of 44 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:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000577	Exotropia
HP:0000602	Ophthalmoplegia
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0003831	Typified by age-related disease onset
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007754	Macular dystrophy

GWAS associations

60 associations (top):

Study	Trait	p-value
GCST001762_816	Obesity-related traits	3.000000e-06
GCST002337_56	Amyotrophic lateral sclerosis (sporadic)	3.000000e-08
GCST005787_30	Heart rate response to exercise	4.000000e-10
GCST006167_79	Mean arterial pressure x alcohol consumption interaction (2df test)	5.000000e-11
GCST006170_18	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	4.000000e-14
GCST006172_38	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	6.000000e-12
GCST006434_87	Systolic blood pressure x alcohol consumption interaction (2df test)	5.000000e-23
GCST006612_39	LDL cholesterol	2.000000e-11
GCST007325_156	General risk tolerance (MTAG)	9.000000e-12
GCST007325_183	General risk tolerance (MTAG)	1.000000e-08
GCST007709_56	General factor of neuroticism	1.000000e-11
GCST007709_60	General factor of neuroticism	2.000000e-11
GCST010002_269	Refractive error	1.000000e-24
GCST010132_11	Processed meat consumption	4.000000e-10
GCST010132_14	Processed meat consumption	2.000000e-15
GCST010132_15	Processed meat consumption	1.000000e-09
GCST010137_2	Cooked vegetable consumption	2.000000e-10
GCST010142_4	Fish- and plant-related diet	2.000000e-12
GCST010142_6	Fish- and plant-related diet	3.000000e-12
GCST010142_63	Fish- and plant-related diet	2.000000e-12
GCST010142_67	Fish- and plant-related diet	1.000000e-10
GCST010142_70	Fish- and plant-related diet	8.000000e-10
GCST010142_89	Fish- and plant-related diet	4.000000e-16
GCST010142_90	Fish- and plant-related diet	7.000000e-15
GCST010244_297	Triglyceride levels	3.000000e-12
GCST010703_306	Brain morphology (MOSTest)	5.000000e-26
GCST010771_4	Osteoarthrosis (time to event)	5.000000e-08
GCST011369_13	Iron status biomarkers (ferritin levels)	8.000000e-21
GCST011461_4	Barrett’s esophagus or Esophageal adenocarcinoma	7.000000e-09
GCST011462_4	Barrett’s esophagus or esophageal adenocarcinoma x sex interaction (2df test)	2.000000e-08

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement
EFO:0009184	heart rate response to exercise
EFO:0004329	alcohol drinking
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008579	risk-taking behaviour
EFO:0007660	neuroticism measurement
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0004918	age at diagnosis
EFO:0004459	ferritin measurement
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004833	neutrophil count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D000080362	Stargardt Disease	C11.270.872; C11.768.585.439.339; C16.320.290.724
C563905	Ulnar-Fibular Ray Defect and Brachydactyly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

262 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
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
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa