LCA5

Summary

LCA5 (lebercilin LCA5, HGNC:31923) is a protein-coding gene on chromosome 6q14.1, encoding Lebercilin (Q86VQ0). Involved in intraflagellar protein (IFT) transport in photoreceptor cilia.

This gene encodes a protein that is thought to be involved in centrosomal or ciliary functions. Mutations in this gene cause Leber congenital amaurosis type V. Alternatively spliced transcript variants are described.

Source: NCBI Gene 167691 — RefSeq curated summary.

At a glance

• Gene–disease (curated): LCA5-related retinopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 932 total — 87 pathogenic, 54 likely-pathogenic
• Phenotypes (HPO): 57
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001122769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31923
Approved symbol	LCA5
Name	lebercilin LCA5
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135338
Ensembl biotype	protein_coding
OMIM	611408
Entrez	167691

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000369846, ENST00000392959, ENST00000467898, ENST00000859359, ENST00000919394, ENST00000951447

RefSeq mRNA: 2 — MANE Select: NM_001122769 NM_001122769, NM_181714

CCDS: CCDS4990

Canonical transcript exons

ENST00000369846 — 8 exons

Exon	Start	End
ENSE00001155691	79489084	79489216
ENSE00001451035	79484991	79487866
ENSE00001451039	79537165	79537430
ENSE00003494816	79492551	79492647
ENSE00003516930	79518705	79519085
ENSE00003527792	79491588	79491730
ENSE00003563588	79493613	79493750
ENSE00003583667	79513212	79513741

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 88.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.6016 / max 106.5709, expressed in 1284 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74512	2.4333	1070
74511	1.3928	662
74513	0.7362	462
74514	0.0267	10
74510	0.0126	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	88.28	gold quality
bronchial epithelial cell	CL:0002328	88.09	gold quality
bronchus	UBERON:0002185	86.58	gold quality
caput epididymis	UBERON:0004358	85.60	gold quality
oviduct epithelium	UBERON:0004804	85.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.88	gold quality
calcaneal tendon	UBERON:0003701	84.59	gold quality
secondary oocyte	CL:0000655	82.45	gold quality
right uterine tube	UBERON:0001302	82.37	gold quality
ventricular zone	UBERON:0003053	82.03	gold quality
ganglionic eminence	UBERON:0004023	81.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.42	gold quality
corpus epididymis	UBERON:0004359	78.92	gold quality
fallopian tube	UBERON:0003889	78.88	gold quality
cauda epididymis	UBERON:0004360	78.76	gold quality
tibialis anterior	UBERON:0001385	78.64	silver quality
cortical plate	UBERON:0005343	77.54	gold quality
islet of Langerhans	UBERON:0000006	77.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.02	gold quality
smooth muscle tissue	UBERON:0001135	75.75	gold quality
tendon	UBERON:0000043	75.45	gold quality
spinal cord	UBERON:0002240	75.27	gold quality
popliteal artery	UBERON:0002250	75.23	gold quality
corpus callosum	UBERON:0002336	75.21	gold quality
tibial artery	UBERON:0007610	75.21	gold quality
medial globus pallidus	UBERON:0002477	74.51	gold quality
descending thoracic aorta	UBERON:0002345	73.93	gold quality
body of uterus	UBERON:0009853	73.87	gold quality
aorta	UBERON:0000947	73.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

93 targeting LCA5, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
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-3143	99.93	71.96	3104
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-519E-5P	99.92	69.62	2358
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-182-5P	99.87	74.03	2589

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• Macular coloboma-type LCA shows genetic heterogeneity and it is not possible to establish a phenotype-genotype correlation with LCA5 and macular coloboma. (PMID:16082399)
• The LCA5 gene on chromosome 6q14 encodes the ciliary protein lebercilin associated with Leber congenital amaurosis type 5. (PMID:17546029)
• Data report the identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in this series (3/179; 1.7%). (PMID:18000884)
• This is the second report of LCA5 mutations causing Leber congenital amaurosis. (PMID:18334959)
• This result shows that mutation in LCA5 is likely to be a rare genetic cause in Koreans (PMID:19172513)
• Leber congenital amaurosis 2 patients with LCA5 mutation had evidence of retained photoreceptors mainly in the central retina; retinal remodeling was present in pericentral regions (PMID:19503738)
• OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin (PMID:19800048)
• A novel LCA5 mutation is present in a Pakistani family with Leber congenital amaurosis and cataracts. (PMID:21850168)
• Identification of novel LCA5 mutations in patients with Leber congenital amaurosis and retinitis pigmentosa. (PMID:23946133)
• This work reveals a higher frequency of LCA5 mutations in a Spanish Leber congenital amaurosis cohort than in other populations. (PMID:24144451)
• The authors report novel biallelic LCA5 mutations, Ala212Pro and Tyr441Cys, as causing cone dystrophy. (PMID:27067258)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lca5	ENSDARG00000076153
mus_musculus	Lca5	ENSMUSG00000032258
rattus_norvegicus	Lca5	ENSRNOG00000009580
drosophila_melanogaster	CG6652	FBGN0036687

Paralogs (1): LCA5L (ENSG00000157578)

Protein

Protein identifiers

Lebercilin — Q86VQ0 (reviewed: Q86VQ0)

Alternative names: Leber congenital amaurosis 5 protein

All UniProt accessions (3): A0A384MDJ7, Q86VQ0, S4R3K6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in intraflagellar protein (IFT) transport in photoreceptor cilia. Plays a role in the ciliary transport of photoreceptors outer segment proteins.

Subunit / interactions. Interacts with NINL. Interacts with OFD1. Interacts with FAM161A. Interacts with components of the IFT complex B.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Cilium basal body. Microtubule organizing center. Centrosome. Cell projection. Cilium.

Tissue specificity. Widely expressed.

Disease relevance. Leber congenital amaurosis 5 (LCA5) [MIM:604537] 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 LCA5 family.

RefSeq proteins (2): NP_001116241, NP_859065 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026188	Lebercilin-like	Family
IPR028933	Lebercilin_dom	Domain

Pfam: PF15619

UniProt features (23 total): sequence variant 6, compositionally biased region 5, region of interest 4, sequence conflict 3, modified residue 2, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VQ0-F1	64.05	0.27

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 (2): 7, 45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 219 (showing top): RORA1_01, GOZGIT_ESR1_TARGETS_DN, TATTATA_MIR374, TGACCTY_ERR1_Q2, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, ATGTTAA_MIR302C, WATANABE_ULCERATIVE_COLITIS_WITH_CANCER_UP, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, DEN_INTERACT_WITH_LCA5, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (3): protein transport (GO:0015031), intraciliary transport (GO:0042073), photoreceptor cell maintenance (GO:0045494)

GO Molecular Function (2): protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (13): nucleoplasm (GO:0005654), nucleolus (GO:0005730), mitochondrion (GO:0005739), centrosome (GO:0005813), centriole (GO:0005814), cilium (GO:0005929), axoneme (GO:0005930), photoreceptor connecting cilium (GO:0032391), ciliary basal body (GO:0036064), sperm midpiece (GO:0097225), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	3
microtubule organizing center	3
cilium	2
binding	2
nuclear lumen	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
transport along microtubule	1
cilium organization	1
retina homeostasis	1
multicellular organismal process	1
cytoplasm	1
intracellular membrane-bounded organelle	1
centriole	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
ciliary transition zone	1
photoreceptor cell cilium	1
sperm flagellum	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCA5	NINL	Q9Y2I6	924
LCA5	USH2A	O75445	908
LCA5	RPGRIP1	Q96KN7	895
LCA5	RD3	Q7Z3Z2	872
LCA5	SPATA7	Q9P0W8	869
LCA5	GUCY2D	Q02846	868
LCA5	AIPL1	Q9NZN9	854
LCA5	RDH12	Q96NR8	845
LCA5	CEP290	O15078	822
LCA5	OFD1	O75665	803
LCA5	LRAT	O95237	798
LCA5	RPE65	Q16518	795
LCA5	IMPDH1	P20839	793
LCA5	CRX	O43186	773
LCA5	IQCB1	Q15051	759

IntAct

42 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
LCA5	SSNA1	psi-mi:“MI:0914”(association)	0.700
SSNA1	LCA5	psi-mi:“MI:0915”(physical association)	0.700
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
LCA5	TFIP11	psi-mi:“MI:0915”(physical association)	0.660
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
TXLNA	LCA5	psi-mi:“MI:0915”(physical association)	0.560
RCOR3	LCA5	psi-mi:“MI:0915”(physical association)	0.560
LCA5	RCOR3	psi-mi:“MI:0915”(physical association)	0.560
LCA5	TXLNA	psi-mi:“MI:0915”(physical association)	0.560
LCA5	GCC1	psi-mi:“MI:0915”(physical association)	0.560
LCA5	SUFU	psi-mi:“MI:0915”(physical association)	0.560
TSPYL1	GPC3	psi-mi:“MI:0914”(association)	0.530
LCA5	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
LCA5	OFD1	psi-mi:“MI:0914”(association)	0.420
LCA5	rep	psi-mi:“MI:0915”(physical association)	0.370
LCA5	IFT56	psi-mi:“MI:0914”(association)	0.350
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
LCA5	MAEA	psi-mi:“MI:0914”(association)	0.350
LCA5	DVL2	psi-mi:“MI:2364”(proximity)	0.270
PCM1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
LCA5	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
SSNA1	LCA5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (147): LCA5 (Two-hybrid), TXLNA (Two-hybrid), LCA5 (Affinity Capture-Western), CEP170 (Affinity Capture-Western), KIAA0753 (Affinity Capture-Western), OFD1 (Affinity Capture-Western), PCM1 (Affinity Capture-Western), SSX2IP (Affinity Capture-Western), PCM1 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), PYCR1 (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), SUPT5H (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), CLUAP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GUX5, A0A1L8GXY6, A0A1W2P884, A2AIW0, A2AM05, A2CE83, A6PWD2, E7F5E1, O60296, P27628, P28290, P60853, Q0VF96, Q28GJ0, Q2KJD6, Q2M243, Q2MJV9, Q3V036, Q4KLH6, Q5R9L2, Q5RHB5, Q5SZL2, Q5U2Y9, Q5U3Z6, Q5U4W1, Q6AW69, Q6DIS8, Q6NRK1, Q6NRX3, Q6P2H3, Q6PCQ0, Q6ZQ06, Q70YC5, Q804T6, Q80ST9, Q86VQ0, Q8BMK0, Q8C115, Q8CFC9, Q8CGZ2

Diamond homologs: A7E3D8, B0CM36, O95447, Q4R3Q7, Q5U2Y9, Q80ST9, Q86VQ0, Q8C0X0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intraflagellar transport	5	52.7×	4e-06
Loss of Nlp from mitotic centrosomes	5	41.7×	4e-06
Loss of proteins required for interphase microtubule organization from the centrosome	5	41.7×	4e-06
AURKA Activation by TPX2	5	40.1×	4e-06
Recruitment of mitotic centrosome proteins and complexes	5	35.8×	5e-06
Regulation of PLK1 Activity at G2/M Transition	5	33.4×	6e-06
Recruitment of NuMA to mitotic centrosomes	5	30.7×	8e-06
Anchoring of the basal body to the plasma membrane	5	29.8×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
smoothened signaling pathway	5	43.1×	2e-05
cilium assembly	6	21.0×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	87
Likely pathogenic	54
Uncertain significance	356
Likely benign	352
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072648	NM_001122769.3(LCA5):c.344T>A (p.Leu115Ter)	Pathogenic
1075356	NM_001122769.3(LCA5):c.240_241del (p.Val81fs)	Pathogenic
1172715	NM_001122769.3(LCA5):c.1368dup (p.Glu457fs)	Pathogenic
1354701	NM_001122769.3(LCA5):c.271G>T (p.Glu91Ter)	Pathogenic
1357373	NM_001122769.3(LCA5):c.67_68insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCGTTTTAGCCGGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAACACCATTATTCTT (p.Tyr23delinsPhePhePhePhePhePhePheXaaXaaXaaXaaArgPheSerArgAspGlyLeuAspLeuLeuThrSerTer)	Pathogenic
1383482	NM_001122769.3(LCA5):c.1326dup (p.Leu443fs)	Pathogenic
1386722	NM_001122769.3(LCA5):c.1187_1191delinsTTACGACAAC (p.Glu396fs)	Pathogenic
1403675	NM_001122769.3(LCA5):c.1312del (p.Thr438fs)	Pathogenic
1413263	NM_001122769.3(LCA5):c.1458C>G (p.Tyr486Ter)	Pathogenic
1421702	NM_001122769.3(LCA5):c.1281dup (p.Leu428fs)	Pathogenic
1422680	NM_001122769.3(LCA5):c.713del (p.Arg238fs)	Pathogenic
1423301	NM_001122769.3(LCA5):c.886_887insT (p.Asn296fs)	Pathogenic
1437939	NM_001122769.3(LCA5):c.1324C>T (p.Gln442Ter)	Pathogenic
1451863	NM_001122769.3(LCA5):c.1507G>T (p.Glu503Ter)	Pathogenic
1452693	NM_001122769.3(LCA5):c.1165G>T (p.Glu389Ter)	Pathogenic
1452766	NM_001122769.3(LCA5):c.166del (p.Ser56fs)	Pathogenic
1454319	NM_001122769.3(LCA5):c.367C>T (p.Gln123Ter)	Pathogenic
1456070	NM_001122769.3(LCA5):c.1375G>T (p.Glu459Ter)	Pathogenic
1456840	NM_001122769.3(LCA5):c.69C>G (p.Tyr23Ter)	Pathogenic
1904400	NM_001122769.3(LCA5):c.536_537del (p.Gln179fs)	Pathogenic
1916309	NM_001122769.3(LCA5):c.766C>T (p.Gln256Ter)	Pathogenic
2000866	NM_001122769.3(LCA5):c.669_672del (p.Lys223fs)	Pathogenic
2003814	NM_001122769.3(LCA5):c.887dup (p.Asn296fs)	Pathogenic
2023889	NM_001122769.3(LCA5):c.644dup (p.Pro216fs)	Pathogenic
2028370	NM_001122769.3(LCA5):c.1669_1673del (p.Val557fs)	Pathogenic
2030061	NM_001122769.3(LCA5):c.1457_1460delinsTTTTTGCCATTGTTTTGCCAT (p.Tyr486fs)	Pathogenic
2032395	NM_001122769.3(LCA5):c.1616C>G (p.Ser539Ter)	Pathogenic
2036012	NM_001122769.3(LCA5):c.1481_1482del (p.Asp494fs)	Pathogenic
2089254	NM_001122769.3(LCA5):c.564_565dup (p.Val189fs)	Pathogenic
2118705	NM_001122769.3(LCA5):c.1430_1434del (p.Glu477fs)	Pathogenic

SpliceAI

1577 predictions. Top by Δscore:

Variant	Effect	Δscore
6:79487867:C:CC	acceptor_gain	1.0000
6:79489082:ACCAT:A	donor_gain	1.0000
6:79489083:CCATC:C	donor_gain	1.0000
6:79489216:CC:C	acceptor_loss	1.0000
6:79489220:T:TC	acceptor_gain	1.0000
6:79489225:C:CT	acceptor_gain	1.0000
6:79489226:G:C	acceptor_gain	1.0000
6:79489227:T:C	acceptor_gain	1.0000
6:79490197:G:C	donor_gain	1.0000
6:79491583:CTCA:C	donor_loss	1.0000
6:79491584:TCA:T	donor_loss	1.0000
6:79491585:CA:C	donor_loss	1.0000
6:79491586:A:AC	donor_gain	1.0000
6:79491586:A:T	donor_loss	1.0000
6:79491587:C:A	donor_loss	1.0000
6:79491587:C:CA	donor_gain	1.0000
6:79491587:CCA:C	donor_gain	1.0000
6:79491587:CCAA:C	donor_gain	1.0000
6:79491611:C:A	donor_gain	1.0000
6:79491726:TGCAG:T	acceptor_gain	1.0000
6:79491727:GCAG:G	acceptor_gain	1.0000
6:79491728:CAG:C	acceptor_gain	1.0000
6:79491728:CAGC:C	acceptor_gain	1.0000
6:79491729:AG:A	acceptor_gain	1.0000
6:79491729:AGC:A	acceptor_loss	1.0000
6:79491731:C:CC	acceptor_gain	1.0000
6:79491731:C:CG	acceptor_loss	1.0000
6:79491732:T:G	acceptor_loss	1.0000
6:79491734:CAG:C	acceptor_gain	1.0000
6:79491735:A:T	acceptor_gain	1.0000

AlphaMissense

4613 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:79493707:C:G	R255P	0.996
6:79513315:A:G	L206P	0.995
6:79493746:A:G	L242P	0.994
6:79513258:A:G	L225P	0.994
6:79513279:C:G	R218P	0.994
6:79492631:A:G	L292P	0.993
6:79493728:A:G	L248P	0.993
6:79493734:A:G	L246P	0.993
6:79513250:C:G	A228P	0.993
6:79513288:A:G	L215P	0.993
6:79513453:A:G	L160P	0.993
6:79513400:A:G	S178P	0.992
6:79513270:A:G	L221S	0.991
6:79513420:A:G	L171P	0.990
6:79513441:T:G	H164P	0.990
6:79513567:A:G	L122P	0.990
6:79487275:A:G	L608S	0.988
6:79513411:C:G	R174P	0.988
6:79513546:A:G	L129P	0.988
6:79513268:C:G	A222P	0.987
6:79513384:C:G	R183P	0.987
6:79492604:C:G	R301P	0.986
6:79492618:A:C	N296K	0.986
6:79492618:A:T	N296K	0.986
6:79493672:C:G	A267P	0.986
6:79487418:A:C	F560L	0.985
6:79487418:A:T	F560L	0.985
6:79487420:A:G	F560L	0.985
6:79493629:A:G	L281P	0.985
6:79513298:C:G	A212P	0.985

dbSNP variants (sampled 300 via entrez): RS1000026946 (6:79537568 C>T), RS1000058457 (6:79539817 G>A,C,T), RS1000162079 (6:79502645 A>T), RS1000207512 (6:79503180 C>A), RS1000341893 (6:79521023 G>T), RS1000363418 (6:79507504 T>C), RS1000518372 (6:79501421 C>G), RS1000631953 (6:79506078 T>C,G), RS1000707885 (6:79519494 G>A), RS1000736247 (6:79520641 T>C), RS1000776817 (6:79526674 G>A,T), RS1000784316 (6:79507856 T>C), RS1000855933 (6:79513529 A>T), RS1000879549 (6:79532989 T>C), RS1000884917 (6:79525893 T>A)

Disease associations

OMIM: gene MIM:611408 | disease phenotypes: MIM:604537, MIM:204000, MIM:268000, MIM:617004

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis 5	Definitive	Autosomal recessive
severe early-childhood-onset retinal dystrophy	Supportive	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
LCA5-related retinopathy	Definitive	AR

Mondo (10): Leber congenital amaurosis 5 (MONDO:0011473), Leber congenital amaurosis (MONDO:0018998), inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis 1 (MONDO:0008764), optic atrophy (MONDO:0003608), retinitis pigmentosa (MONDO:0019200), LCA5-related retinopathy (MONDO:0100445), retinal disorder (MONDO:0005283), polycystic liver disease 2 (MONDO:0014860), severe early-childhood-onset retinal dystrophy (MONDO:0009549)

Orphanet (4): Leber congenital amaurosis (Orphanet:65), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Isolated polycystic liver disease (Orphanet:2924)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000533	Chorioretinal atrophy
HP:0000540	Hypermetropia
HP:0000541	Retinal detachment
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:0000572	Visual loss
HP:0000577	Exotropia
HP:0000613	Photophobia
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0000729	Autistic behavior
HP:0001103	Abnormal macular morphology
HP:0001116	Macular pseudocoloboma
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001483	Eye poking

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000932_3	Hoarding	7.000000e-07
GCST001872_3	Presence of antiphospholipid antibodies	7.000000e-06
GCST002726_61	Glucose homeostasis traits	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
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
C536602	Amaurosis congenita of Leber, type 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	4
methylmercuric chloride	decreases expression	2
trichostatin A	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	2
Valproic Acid	decreases methylation, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
manganese chloride	increases abundance, increases expression	1
cylindrospermopsin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Manganese	increases expression, increases abundance	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	increases expression	1
Aflatoxin B1	decreases methylation	1
Gold Compounds	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1
Magnetite Nanoparticles	increases methylation	1

Clinical trials (associated diseases)

293 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
NCT05244304	PHASE3	COMPLETED	Phase 3, Randomized, Placebo-Controlled Study of Tinlarebant to Explore Safety and Efficacy in Adolescent Stargardt Disease
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)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
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
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
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
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
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
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