TULP1

Summary

TULP1 (TUB like protein 1, HGNC:12423) is a protein-coding gene on chromosome 6p21.31, encoding Tubby-related protein 1 (O00294). Required for normal development of photoreceptor synapses.

This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15.

Source: NCBI Gene 7287 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Leber congenital amaurosis 15 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 871 total — 81 pathogenic, 54 likely-pathogenic
• Phenotypes (HPO): 61
• MANE Select transcript: NM_003322

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12423
Approved symbol	TULP1
Name	TUB like protein 1
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	TUBL1, LCA15
Ensembl gene	ENSG00000112041
Ensembl biotype	protein_coding
OMIM	602280
Entrez	7287

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 retained_intron

ENST00000229771, ENST00000322263, ENST00000373892, ENST00000428978, ENST00000448446, ENST00000495781, ENST00000496434, ENST00000614066

RefSeq mRNA: 2 — MANE Select: NM_003322 NM_001289395, NM_003322

CCDS: CCDS4807, CCDS75436

Canonical transcript exons

ENST00000229771 — 15 exons

Exon	Start	End
ENSE00000747173	35509827	35509928
ENSE00000747197	35510861	35511010
ENSE00000747243	35512180	35512270
ENSE00000849646	35497874	35498460
ENSE00000849647	35512639	35512690
ENSE00001785737	35512812	35512896
ENSE00002494357	35499981	35500152
ENSE00002703707	35509634	35509750
ENSE00003471311	35506003	35506173
ENSE00003483609	35503737	35503848
ENSE00003505030	35511648	35511806
ENSE00003508004	35505741	35505853
ENSE00003553276	35506274	35506279
ENSE00003553292	35503559	35503657
ENSE00003573216	35509209	35509312

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 78.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5767 / max 172.3708, expressed in 67 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73289	0.3006	16
73286	0.1166	36
73288	0.0752	10
73290	0.0621	13
203975	0.0131	8
73287	0.0091	5

Top tissues by expression

275 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	78.59	gold quality
tendon of biceps brachii	UBERON:0008188	71.41	silver quality
retina	UBERON:0000966	71.02	silver quality
pigmented layer of retina	UBERON:0001782	71.02	silver quality
sural nerve	UBERON:0015488	63.39	silver quality
neuron projection bundle connecting eye with brain	UBERON:0004904	62.49	silver quality
ventricular zone	UBERON:0003053	62.19	gold quality
left uterine tube	UBERON:0001303	59.95	gold quality
body of uterus	UBERON:0009853	59.84	gold quality
vagina	UBERON:0000996	59.36	gold quality
diaphragm	UBERON:0001103	58.43	gold quality
ectocervix	UBERON:0012249	58.08	gold quality
skin of leg	UBERON:0001511	57.93	gold quality
medial globus pallidus	UBERON:0002477	57.92	gold quality
prostate gland	UBERON:0002367	57.35	gold quality
trabecular bone tissue	UBERON:0002483	57.25	gold quality
right ovary	UBERON:0002118	57.04	gold quality
decidua	UBERON:0002450	56.55	gold quality
quadriceps femoris	UBERON:0001377	56.49	gold quality
vastus lateralis	UBERON:0001379	56.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	56.36	gold quality
skin of abdomen	UBERON:0001416	55.97	gold quality
zone of skin	UBERON:0000014	55.86	gold quality
pancreatic ductal cell	CL:0002079	55.81	silver quality
smooth muscle tissue	UBERON:0001135	55.73	gold quality
esophagus mucosa	UBERON:0002469	55.37	gold quality
left ovary	UBERON:0002119	55.30	gold quality
endocervix	UBERON:0000458	55.28	gold quality
uterine cervix	UBERON:0000002	55.09	gold quality
ganglionic eminence	UBERON:0004023	55.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	49.36
E-ANND-3	yes	2.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting TULP1, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4755-3P	98.77	65.59	1915

Literature-anchored findings (GeneRIF, showing 20)

• The affected members of the Surinamese family have a severe early-onset form of autosomal recessive retinitis pigmentosa, which is caused by compound heterozygous mutations in the TULP1 gene. (PMID:17620573)
• Mutation in the TULP1 gene is a rare cause of LCA/EORD (Leber congenital amaurosis or early-onset retinal degeneration. (PMID:17962469)
• A novel splice-site mutation of TULP1, c.1495+2_1495+3insT, underlying autosomal recessive early-onset RP in a consanguineous Israeli Muslim Arab family. (PMID:18432314)
• Tubby and Tulp1 function as phagocytosis sigmals (eat-me) for retinal pigment epithelium cells and other phagocytes. (PMID:19837063)
• Tubby and Tulp1 are bridging molecules with their N-terminal region as MERTK-binding domain and C-terminal region as phagocytosis prey-binding domain. (PMID:20978472)
• Pathogenic mutations in TULP1 are responsible for the autosomal recessive retinitis pigmentosa phenotype in these consanguineous Pakistani families, with a single ancestral mutation in TULP1 causing the disease phenotype in 4 of 5 families. (PMID:21987678)
• Homozygous autosomal recessive retinitis pigmentosa-causing mutations have been found in three Indian families. These included a missense mutation in TULP1. (PMID:22605927)
• One recurrent (c.1138A>G; p.Thr380Ala) and one novel (c.1445G>A; p.Arg482Gln) mutations in TULP1 have been identified in Pakistani families with early-onset retinitis pigmentosa. (PMID:22665969)
• The single nucleotide polymorphisms rs4374383 and rs9380516 were linked to the functionally related genes MERTK and TULP1, which encode factors involved in phagocytosis of apoptotic cells by macrophages. (PMID:22841784)
• Maternal uniparental isodisomy of chromosome 6 unmasked a mutation in the TULP1 gene as a novel cause of cone dysfunction. (PMID:23499059)
• This study highlights the value of the broad sequencing strategy of exome sequencing for disease gene identification in Leber congenital amaurosis, over other existing methods. (PMID:24547928)
• Tubby and Tulp1 mediated phagocytosis through MerTK-dependent signaling with non-muscle myosin II redistribution leading to colocalization of phagocytosed vesicles with rearranged NMMIIA. (PMID:24664737)
• Retinal degeneration with TULP1 mutations leads to a small central island of residual foveal cones at early ages which are less sensitive than expected from the residual structure. (PMID:25074776)
• The TULP1 allele p.Gln301* represents a founder mutation on the Arabian Peninsula and is associated with a recognisable congenital recessive rod-cone dystrophy phenotype in the homozygous state. (PMID:25342276)
• Data suggest that mutant tubby like protein 1 (TULP1) proteins are misfolded and accumulate within the endoplasmic reticulum (ER) leading to induction of the unfolded protein response (UPR) stress response complex. (PMID:26427415)
• photoreceptor degeneration caused by missense mutations via endoplasmic reticulum unfolded protein response (PMID:26987071)
• Pathogenic mutations in TULP1 are responsible for the retinitis pigmentosa phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. (PMID:27440997)
• A novel homozygous missense mutation p.P388S in TULP1 causes protein instability and retinitis pigmentosa. (PMID:33907372)
• TULP1 related retinal dystrophy: report of rare and novel variants with a previously undescribed phenotype in two cases. (PMID:34865612)
• Natural history and biomarkers of retinal dystrophy caused by the biallelic TULP1 variant c.148delG. (PMID:36128853)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tulp1a	ENSDARG00000075295
danio_rerio	tulp1b	ENSDARG00000078210
		ENSDARG00000100478
mus_musculus	Tulp1	ENSMUSG00000037446
rattus_norvegicus	Tulp1	ENSRNOG00000000507
drosophila_melanogaster	ktub	FBGN0015721
caenorhabditis_elegans		WBGENE00006655

Paralogs (5): TULP3 (ENSG00000078246), TULP2 (ENSG00000104804), WDR35 (ENSG00000118965), TULP4 (ENSG00000130338), TUB (ENSG00000166402)

Protein

Protein identifiers

Tubby-related protein 1 — O00294 (reviewed: O00294)

Alternative names: Tubby-like protein 1

All UniProt accessions (3): O00294, A0A087WT25, Q5TGM7

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells. Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages.

Subunit / interactions. Homodimer. May interact with ABCF1, PSIP1, ZEB1 and HMGB2 (Potential). Interacts with DNM1. Interacts with F-actin. Interacts with TUB. Interacts with TYRO3.

Subcellular location. Cytoplasm. Cell membrane. Secreted. Synapse.

Tissue specificity. Retina-specific.

Disease relevance. Retinitis pigmentosa 14 (RP14) [MIM:600132] 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. Leber congenital amaurosis 15 (LCA15) [MIM:613843] A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TUB family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00294-1	1	yes
O00294-2	2

RefSeq proteins (2): NP_001276324, NP_003313* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000007	Tubby_C	Domain
IPR018066	Tubby_C_CS	Conserved_site
IPR025659	Tubby-like_C	Homologous_superfamily

Pfam: PF01167

UniProt features (47 total): sequence variant 18, strand 16, helix 5, compositionally biased region 4, chain 1, region of interest 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3C5N	X-RAY DIFFRACTION	1.8
2FIM	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00294-F1	66.10	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (13): retina homeostasis (GO:0001895), phagocytosis, recognition (GO:0006910), visual perception (GO:0007601), dendrite development (GO:0016358), eye photoreceptor cell development (GO:0042462), photoreceptor cell maintenance (GO:0045494), positive regulation of phagocytosis (GO:0050766), detection of light stimulus involved in visual perception (GO:0050908), retina development in camera-type eye (GO:0060041), protein localization to cilium (GO:0061512), protein localization to photoreceptor outer segment (GO:1903546), phagocytosis (GO:0006909), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (11): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), cell projection (GO:0042995), axon terminus (GO:0043679), synapse (GO:0045202), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
phagocytosis	2
anatomical structure development	2
tissue homeostasis	1
cell recognition	1
cargo receptor activity	1
sensory perception of light stimulus	1
neuron projection development	1
eye photoreceptor cell differentiation	1
photoreceptor cell development	1
retina homeostasis	1
multicellular organismal process	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
visual perception	1
detection of light stimulus involved in sensory perception	1
camera-type eye development	1
protein localization to organelle	1
protein localization to non-motile cilium	1
endocytosis	1
transport	1
cellular process	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
actin binding	1
protein-containing complex binding	1
binding	1
photoreceptor cell cilium	1
cytoplasm	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
neuron projection terminus	1
presynapse	1
distal axon	1
cell junction	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TULP1	MERTK	Q12866	949
TULP1	RPE65	Q16518	918
TULP1	AIPL1	Q9NZN9	915
TULP1	LRAT	O95237	894
TULP1	RDH12	Q96NR8	892
TULP1	RPGRIP1	Q96KN7	868
TULP1	GUCY2D	Q02846	861
TULP1	SPATA7	Q9P0W8	861
TULP1	CRX	O43186	844
TULP1	CERKL	Q49MI3	831
TULP1	IMPDH1	P20839	828
TULP1	GAS6	Q14393	828
TULP1	PRPH2	P23942	809
TULP1	ABCA4	P78363	806
TULP1	PDE6A	P16499	801
TULP1	EYS	Q5T1H1	801

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TULP1	NRXN1	psi-mi:“MI:0914”(association)	0.510
TULP1	FYN	psi-mi:“MI:0915”(physical association)	0.400
TULP1	GRB2	psi-mi:“MI:0915”(physical association)	0.400
NCK1	TULP1	psi-mi:“MI:0915”(physical association)	0.400
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
NRXN1	TULP1	psi-mi:“MI:0915”(physical association)	0.000
ARHGAP26	TULP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): TULP1 (Affinity Capture-MS), TULP1 (Affinity Capture-MS), TULP1 (Affinity Capture-MS)

ESM2 similar proteins: B2KF05, B2RRD7, B3MDU3, B4MKC7, E1BBG2, E1BLT8, O00294, O00295, O70318, O75386, O88413, O88808, O94953, P46686, P50586, P50607, P53814, P55201, P97820, Q03111, Q12873, Q2THW9, Q3UHD9, Q5EA28, Q5SQI0, Q6MG11, Q6P1G2, Q6PKG0, Q6ZQ58, Q6ZRS2, Q86UR5, Q8BGT6, Q8BRB7, Q8CGU4, Q8CI12, Q8IY37, Q8N3F8, Q8N4C8, Q8NHM5, Q91VY5

Diamond homologs: A8WN62, B0WI30, B0XFQ9, B3MDU3, B3NJY0, B4H4X0, B4I7J9, B4J6R7, B4KNA9, B4LMR9, B4MKC7, B4P9H8, B4QFM2, O00294, O00295, O75386, O88413, O88808, P46686, P50586, P50607, Q09306, Q0WPY0, Q10LG8, Q16IR1, Q16KI5, Q28X18, Q2QXB2, Q53PP5, Q5QM27, Q688Y7, Q68Y48, Q69U54, Q6NPQ1, Q6Z2G9, Q75HX5, Q7PZK5, Q7XSV4, Q86PC9, Q8GVE5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	81
Likely pathogenic	54
Uncertain significance	300
Likely benign	334
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1046380	NM_003322.6(TULP1):c.1087G>C (p.Gly363Arg)	Pathogenic
1065768	NM_003322.6(TULP1):c.187G>T (p.Gly63Ter)	Pathogenic
1184552	NM_003322.6(TULP1):c.1066C>A (p.Pro356Thr)	Pathogenic
1184553	NC_000006.12:g.35506278_35506281del	Pathogenic
1297129	NM_003322.6(TULP1):c.487C>T (p.Gln163Ter)	Pathogenic
1366826	NM_003322.6(TULP1):c.1258C>A (p.Arg420Ser)	Pathogenic
1391250	NM_003322.6(TULP1):c.726del (p.Gly244fs)	Pathogenic
1407372	NM_003322.6(TULP1):c.239_251del (p.Gln80fs)	Pathogenic
1409684	NM_003322.6(TULP1):c.1430_1453del (p.Leu477_Thr484del)	Pathogenic
1410806	NM_003322.6(TULP1):c.901dup (p.Gln301fs)	Pathogenic
1446615	NM_003322.6(TULP1):c.1351C>T (p.Gln451Ter)	Pathogenic
1451376	NM_003322.6(TULP1):c.1165C>T (p.Gln389Ter)	Pathogenic
1453373	NM_003322.6(TULP1):c.307dup (p.Arg103fs)	Pathogenic
1472762	NM_003322.6(TULP1):c.1513C>T (p.Gln505Ter)	Pathogenic
1675201	NM_003322.6(TULP1):c.790C>T (p.Gln264Ter)	Pathogenic
1943495	NM_003322.6(TULP1):c.859G>T (p.Glu287Ter)	Pathogenic
1950198	NM_003322.6(TULP1):c.1453_1460del (p.Gln485fs)	Pathogenic
1975106	NM_003322.6(TULP1):c.368del (p.Glu123fs)	Pathogenic
1977826	NM_003322.6(TULP1):c.1560C>G (p.Tyr520Ter)	Pathogenic
198784	NM_003322.6(TULP1):c.725_728del (p.Pro242fs)	Pathogenic
2009140	NM_003322.6(TULP1):c.1297G>T (p.Glu433Ter)	Pathogenic
2049378	NM_003322.6(TULP1):c.952C>T (p.Arg318Ter)	Pathogenic
2062606	NM_003322.6(TULP1):c.152_302del151 (p.Cys53fs)	Pathogenic
2136379	NM_003322.6(TULP1):c.1081C>T (p.Arg361Ter)	Pathogenic
2136381	NM_003322.6(TULP1):c.999+5G>C	Pathogenic
2166200	NM_003322.6(TULP1):c.1561C>A (p.Pro521Thr)	Pathogenic
2698982	NM_003322.6(TULP1):c.1171_1172insTTGGCCGGGCGCGGTGGCGCACGCCGGGAATCCCCGCACGATGGGAGGCCGAGGCCCGCGGATCACGTGGTCAGGAGATCGAGGCCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAGAACCCACAGCGTG (p.Gly391fs)	Pathogenic
2734854	NM_003322.6(TULP1):c.627del (p.Ser210fs)	Pathogenic
2747418	NM_003322.6(TULP1):c.780_783del (p.Lys261fs)	Pathogenic
2757427	NM_003322.6(TULP1):c.982dup (p.Leu328fs)	Pathogenic

SpliceAI

2300 predictions. Top by Δscore:

Variant	Effect	Δscore
6:35499973:GTACT:G	donor_loss	1.0000
6:35499975:A:AC	donor_gain	1.0000
6:35499975:ACTC:A	donor_loss	1.0000
6:35499976:C:CC	donor_gain	1.0000
6:35499976:CTC:C	donor_loss	1.0000
6:35499977:TCA:T	donor_loss	1.0000
6:35499978:CA:C	donor_loss	1.0000
6:35499979:A:AC	donor_gain	1.0000
6:35499979:AC:A	donor_loss	1.0000
6:35499979:ACGGT:A	donor_gain	1.0000
6:35499980:C:CA	donor_gain	1.0000
6:35499980:CG:C	donor_gain	1.0000
6:35499980:CGG:C	donor_gain	1.0000
6:35499980:CGGT:C	donor_gain	1.0000
6:35499980:CGGTC:C	donor_gain	1.0000
6:35500148:CTAGC:C	acceptor_gain	1.0000
6:35500158:G:C	acceptor_gain	1.0000
6:35500158:G:GC	acceptor_gain	1.0000
6:35500164:C:CT	acceptor_gain	1.0000
6:35500164:C:T	acceptor_gain	1.0000
6:35500165:A:T	acceptor_gain	1.0000
6:35500171:G:C	acceptor_gain	1.0000
6:35500171:G:GC	acceptor_gain	1.0000
6:35503553:GCTCA:G	donor_loss	1.0000
6:35503554:CTCA:C	donor_loss	1.0000
6:35503555:TCACA:T	donor_loss	1.0000
6:35503556:CACAT:C	donor_loss	1.0000
6:35503557:A:AC	donor_gain	1.0000
6:35503558:C:CC	donor_gain	1.0000
6:35503558:CATTT:C	donor_gain	1.0000

AlphaMissense

3531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:35498414:G:C	F514L	1.000
6:35498414:G:T	F514L	1.000
6:35498416:A:G	F514L	1.000
6:35500006:G:C	N490K	1.000
6:35500006:G:T	N490K	1.000
6:35500009:C:A	K489N	1.000
6:35500009:C:G	K489N	1.000
6:35500039:G:C	F479L	1.000
6:35500039:G:T	F479L	1.000
6:35500041:A:G	F479L	1.000
6:35503824:G:C	F379L	1.000
6:35503824:G:T	F379L	1.000
6:35503826:A:G	F379L	1.000
6:35505750:C:T	G368E	1.000
6:35498415:A:G	F514S	0.999
6:35498436:C:T	G507D	0.999
6:35498445:A:G	L504P	0.999
6:35500003:G:C	F491L	0.999
6:35500003:G:T	F491L	0.999
6:35500004:A:G	F491S	0.999
6:35500005:A:G	F491L	0.999
6:35500007:T:A	N490I	0.999
6:35500010:T:A	K489M	0.999
6:35500040:A:C	F479C	0.999
6:35500040:A:G	F479S	0.999
6:35500041:A:C	F479V	0.999
6:35500041:A:T	F479I	0.999
6:35500046:A:G	L477P	0.999
6:35500046:A:T	L477H	0.999
6:35500094:A:G	L461P	0.999

dbSNP variants (sampled 300 via entrez): RS1000149543 (6:35497991 G>C), RS1000170007 (6:35510524 A>G), RS1000419556 (6:35508005 G>C), RS1000534213 (6:35503306 T>C), RS1000703237 (6:35502132 T>C), RS1000780868 (6:35514440 C>T), RS1000872720 (6:35499559 C>T), RS1000942285 (6:35506021 G>A,C), RS1001153126 (6:35499773 T>G), RS1001605008 (6:35507922 C>G), RS1001825603 (6:35513545 G>A), RS1001886614 (6:35509116 G>A), RS1002110957 (6:35498039 G>C,T), RS1002173048 (6:35513372 G>A), RS1002555460 (6:35506150 G>A,C)

Disease associations

OMIM: gene MIM:602280 | disease phenotypes: MIM:600132, MIM:613843, MIM:204000, MIM:268000, MIM:174200, MIM:248200

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 14	Definitive	Autosomal recessive
Leber congenital amaurosis 15	Strong	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Leber congenital amaurosis 15	Definitive	AR

Mondo (11): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 14 (MONDO:0010827), Leber congenital amaurosis 15 (MONDO:0013457), Leber congenital amaurosis (MONDO:0018998), retinitis pigmentosa (MONDO:0019200), retinal degeneration (MONDO:0004580), polydactyly, postaxial, type A1 (MONDO:0008266), syndactyly (MONDO:0021002), brachydactyly (MONDO:0021004), Leber congenital amaurosis 1 (MONDO:0008764), Stargardt disease (MONDO:0019353)

Orphanet (4): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65), Retinitis pigmentosa (Orphanet:791), Stargardt disease (Orphanet:827)

HPO phenotypes

61 total (30 of 61 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000550	Undetectable electroretinogram
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000729	Autistic behavior
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001623_3	Hepatitis C induced liver fibrosis	5.000000e-07
GCST006976_91	Macular thickness	6.000000e-09
GCST012227_974	Hip circumference adjusted for BMI	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D059327	Brachydactyly	C05.660.585.262; C16.131.621.585.262
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D012162	Retinal Degeneration	C11.270.612; C11.768.585
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
D013576	Syndactyly	C05.116.099.370.894.819; C05.660.585.800; C05.660.906.819; C16.131.621.585.800; C16.131.621.906.819

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Testosterone	increases expression	1
Cadmium Chloride	increases abundance, decreases expression	1
Particulate Matter	increases expression, increases abundance	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
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
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
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis