LRAT

Summary

LRAT (lecithin retinol acyltransferase, HGNC:6685) is a protein-coding gene on chromosome 4q32.1, encoding Lecithin retinol acyltransferase (O95237). Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters.

The protein encoded by this gene localizes to the endoplasmic reticulum, where it catalyzes the esterification of all-trans-retinol into all-trans-retinyl ester. This reaction is an important step in vitamin A metabolism in the visual system. Mutations in this gene have been associated with early-onset severe retinal dystrophy and Leber congenital amaurosis 14. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9227 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 285 total — 25 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 78
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_004744

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6685
Approved symbol	LRAT
Name	lecithin retinol acyltransferase
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Aliases	LCA14
Ensembl gene	ENSG00000121207
Ensembl biotype	protein_coding
OMIM	604863
Entrez	9227

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000336356, ENST00000499392, ENST00000500890, ENST00000502474, ENST00000502525, ENST00000507827, ENST00000510733, ENST00000510919, ENST00000911747, ENST00000911748

RefSeq mRNA: 2 — MANE Select: NM_004744 NM_001301645, NM_004744

CCDS: CCDS3789

Canonical transcript exons

ENST00000336356 — 3 exons

Exon	Start	End
ENSE00001344788	154744326	154744866
ENSE00001516654	154744000	154744222
ENSE00003616748	154748984	154753120

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 86.41.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9836 / max 260.0290, expressed in 419 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50184	1.3962	270
50181	0.4414	208
50182	0.0848	43
50185	0.0611	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	86.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.32	gold quality
gall bladder	UBERON:0002110	78.15	gold quality
jejunal mucosa	UBERON:0000399	75.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.18	gold quality
duodenum	UBERON:0002114	72.66	gold quality
right lobe of liver	UBERON:0001114	71.63	gold quality
muscle layer of sigmoid colon	UBERON:0035805	70.13	gold quality
spinal cord	UBERON:0002240	70.10	gold quality
tibial nerve	UBERON:0001323	68.56	gold quality
left lobe of thyroid gland	UBERON:0001120	68.06	gold quality
nucleus accumbens	UBERON:0001882	67.50	gold quality
right testis	UBERON:0004534	67.23	gold quality
thyroid gland	UBERON:0002046	67.19	gold quality
hypothalamus	UBERON:0001898	66.19	gold quality
left testis	UBERON:0004533	66.09	gold quality
right lobe of thyroid gland	UBERON:0001119	65.81	gold quality
islet of Langerhans	UBERON:0000006	65.27	gold quality
testis	UBERON:0000473	65.24	gold quality
sural nerve	UBERON:0015488	64.79	silver quality
small intestine	UBERON:0002108	64.59	gold quality
caudate nucleus	UBERON:0001873	63.99	gold quality
liver	UBERON:0002107	63.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.85	gold quality
anterior cingulate cortex	UBERON:0009835	61.49	gold quality
cingulate cortex	UBERON:0003027	61.44	gold quality
amygdala	UBERON:0001876	61.38	gold quality
pancreas	UBERON:0001264	60.01	gold quality
prostate gland	UBERON:0002367	59.95	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	17.23
E-CURD-11	no	38.53
E-MTAB-6379	no	8.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA4, RARB, RARG

miRNA regulators (miRDB)

213 targeting LRAT, 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-4776-3P	100.00	68.73	1340
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-128-3P	99.95	71.17	2484

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 25)

• LRAT expression is higher in renal tumors with an indolent biological behavior (PMID:14581364)
• Conserved residues Cys-161 and His-60 form the essential catalytic dyad of LRAT that represents a novel thiol protease motif, which functions in an acyltransferase reaction. (PMID:14596594)
• LRAT has a role in preventing progression of invasive bladder cancer (PMID:15161698)
• Results provide evidence that multiple LRAT mRNA transcripts, which are expressed in a tissue-specific manner, may result from differential splicing of the 5’UTR region and the use of multiple polyadenylation signals in the 3’UTR. (PMID:15474300)
• LRAT has a role in retinoid absorption and storage (PMID:16115871)
• These experiments are consistent with an expanded role for LRAT function as a protein palmitoyl transferase. (PMID:16939223)
• The phenotype of patients with mutations in LRAT is similar to that of patients with mutations in RPE65, suggesting the need to systematically screen both genes in case of typical phenotype. (PMID:17011878)
• LRAT mutations are likely a rare cause of Leber congenital amaurosis among patients from North America. (PMID:17438524)
• Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver. (PMID:18544127)
• transcriptional regulation is aberrant in human prostate cancer and involves GATA transcription factors in normal prostate epithelial cells (PMID:18652909)
• Data show that overexpression of human LRAT specifically in mice oral basal epithelial cells makes these cells more sensitive to carcinogen induced tumorigenesis. (PMID:19471114)
• proximal region together with basal transcription factors may be sufficient to drive Lrat expression. (PMID:19665987)
• This study showed that malignant melanoma cells are able to esterify all-trans retinol and subsequently isomerize all-trans retinyl esters (RE) into 11-cis retinol, whereas their benign counterparts-melanocytes are not able to catalyze these reactions. (PMID:21465477)
• A genetic defect was identified in LRAT as a novel cause of retinitis punctata albescens. (PMID:22559933)
• LRAT mutations cause a severe, early childhood onset, progressive retinal dystrophy. (PMID:22570351)
• Data show that acyl-modified forms of HRAS-like tumor suppressors HRASLS2 and HRASLS3 mimicking lipolytic activity of lecithin retinol acyltransferase LRAT. (PMID:22605381)
• Functional hepatic stellate cells coexpressing both LRAT and CRBP-1, that continue to maintain the ability to store vitamin A, contribute in part to the development of portal and parenchymal fibrogenesis in patients with viral hepatitis. (PMID:23890161)
• high LRAT expression in melanoma might be important in removing retinol as substrate for RA production, thereby inducing signalling pathways leading to dedifferentiation, proliferation and anti-apoptosis (PMID:24433184)
• Lecithin-retinol acyltransferase is a thermostable and highly active enzyme with a likely mode of interfacial activation. (PMID:24613493)
• lecithin retinol acyltransferase affects all-trans retinoic acid levels and has a role in retinoid sensitivity in malignant melanoma cells. (PMID:25236354)
• LRAT hypermethylation was associated with decreased mRNA levels in colorectal cancer clinical specimens. (PMID:25260806)
• These findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family (PMID:25383759)
• instability of LRAT(E14L) did not abrogate the production of the visual chromophore in a cell-based assay. Instead, expression of LRAT(E14L) led to a rapid increase in cellular levels of retinoic acid upon retinoid supplementation. (PMID:28758396)
• The genetic analysis performed on our proband showed a novel homozygous mutation on codon 119 of lecithin-cholesterol acyltransferase gene that causes the substitution of glycine by aspartate (PMID:28942093)
• The c.541-15T>G mutation in LRAT results in aberrant splicing and is therefore predicted to be causal for the early onset retinitis pigmentosa in this family. (PMID:29973277)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrata	ENSDARG00000037278
danio_rerio	lratb.1	ENSDARG00000096594
mus_musculus	Lrat	ENSMUSG00000028003
rattus_norvegicus	Lrat	ENSRNOG00000025608

Paralogs (7): PLAAT1 (ENSG00000127252), PLAAT4 (ENSG00000133321), PLAAT2 (ENSG00000133328), LRATD1 (ENSG00000162981), PLAAT5 (ENSG00000168004), LRATD2 (ENSG00000168672), PLAAT3 (ENSG00000176485)

Protein

Protein identifiers

Lecithin retinol acyltransferase — O95237 (reviewed: O95237)

Alternative names: Phosphatidylcholine–retinol O-acyltransferase

All UniProt accessions (2): D6RC94, O95237

UniProt curated annotations — full annotation on UniProt →

Function. Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters. Retinyl esters are storage forms of vitamin A. LRAT plays a critical role in vision. It provides the all-trans retinyl ester substrates for the isomerohydrolase which processes the esters into 11-cis-retinol in the retinal pigment epithelium; due to a membrane-associated alcohol dehydrogenase, 11 cis-retinol is oxidized and converted into 11-cis-retinaldehyde which is the chromophore for rhodopsin and the cone photopigments. Required for the survival of cone photoreceptors and correct rod photoreceptor cell morphology.

Subcellular location. Endoplasmic reticulum membrane. Rough endoplasmic reticulum. Endosome. Multivesicular body. Cytoplasm. Perinuclear region.

Tissue specificity. Hepatic stellate cells and endothelial cells (at protein level). Found at high levels in testis and liver, followed by retinal pigment epithelium, small intestine, prostate, pancreas and colon. Low expression observed in brain. In fetal tissues, expressed in retinal pigment epithelium and liver, and barely in the brain.

Disease relevance. Leber congenital amaurosis 14 (LCA14) [MIM:613341] 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.

Activity regulation. Inhibited by all-trans-retinyl alpha-bromoacetate and N-boc-L-biocytinyl-11-aminoundecane chloro-methyl ketone (BACMK).

Induction. LRAT activity is up-regulated by dietary vitamin A. Under conditions of vitamin A depletion, LRAT expression in the liver is induced by retinoic acid.

Pathway. Cofactor metabolism; retinol metabolism.

Similarity. Belongs to the H-rev107 family.

RefSeq proteins (2): NP_001288574, NP_004735* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007053	LRAT_dom	Domain
IPR042288	LRAT	Family

Pfam: PF04970

Enzyme classification (BRENDA):

• EC 2.3.1.135 — phosphatidylcholine-retinol O-acyltransferase (BRENDA: 8 organisms, 95 substrates, 28 inhibitors, 38 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALL-TRANS-RETINOL	0.0001–0.055	18
RETINOL-[CELLULAR-RETINOL-BINDING-PROTEIN]	0.0002–0.001	3
11-CIS-RETINOL-[CELLULAR RETINOL-BINDING PROTEIN	0.0023–0.0113	2
ALL-TRANS-RETINOL-[CELLULAR RETINOL-BINDING PROT	0.0003–0.0288	2
RETINOL	0.0004–0.0006	2
11-CIS-RETINOL	0.006	1
ALL-TRANS-RETINOL-[CELLULAR-RETINOL-BINDING-PROT	0.0002	1
DIPALMITOYLPHOSPHATIDYLCHOLINE	0.0014	1
RETINOL-(CELLULAR-RETINOL-BINDING PROTEIN) TYPE	0.0002	1
RETINOL-(CELLULAR-RETINOL-BINDING-PROTEIN)	0.0005	1
RETINOL-[CELLULAR-RETINOL-BINDING-PROTEINTYPE II	0.0003	1

Catalyzed reactions (Rhea), 6 shown:

• all-trans-retinol–[retinol-binding protein] + a 1,2-diacyl-sn-glycero-3-phosphocholine = apo–[retinol-binding protein] + an all-trans-retinyl ester + a 2-acyl-sn-glycero-3-phosphocholine (RHEA:17469)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + all-trans-retinol = all-trans-retinyl hexadecanoate + 2-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:43904)
• 1,2-diheptanoyl-sn-glycero-3-phosphocholine + all-trans-retinol–[retinol-binding protein] = all-trans-retinyl heptanoate + 2-heptanoyl-sn-glycero-3-phosphocholine + apo–[retinol-binding protein] (RHEA:55320)
• 1,2-dioctanoyl-sn-glycero-3-phosphocholine + all-trans-retinol–[retinol-binding protein] = 2-octanoyl-sn-glycero-3-phosphocholine + all-trans-retinyl octanoate + apo–[retinol-binding protein] (RHEA:56240)
• all-trans-retinol–[retinol-binding protein] + 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine = apo–[retinol-binding protein] + all-trans-retinyl hexadecanoate + 2-hexadecanoyl-sn-glycero-3-phosphocholine (RHEA:56244)
• 1,2-didodecanoyl-sn-glycero-3-phosphocholine + all-trans-retinol–[retinol-binding protein] = 2-dodecanoyl-sn-glycero-3-phosphocholine + all-trans-retinyl dodecanoate + apo–[retinol-binding protein] (RHEA:56248)

UniProt features (16 total): mutagenesis site 5, active site 3, topological domain 2, sequence variant 2, chain 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95237-F1	83.69	0.50

Functional residue map

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

Catalytic / active sites (3): 60; 72; 161 (acyl-thioester intermediate)

Mutagenesis-validated functional residues (5):

Position	Phenotype
161	loss of activity.
168	loss of activity.
168	does not affect activity.
182	does not affect activity.
208	does not affect activity.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9918442	Defective visual phototransduction due to LRAT loss of function
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction
R-HSA-2453864	Retinoid cycle disease events
R-HSA-2474795	Diseases associated with visual transduction
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-9675143	Diseases of the neuronal system
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 277 (showing top): BENPORATH_ES_WITH_H3K27ME3, chr4q32, GOBP_RESPONSE_TO_PEPTIDE, GCANCTGNY_MYOD_Q6, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, PID_CONE_PATHWAY, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, BILD_HRAS_ONCOGENIC_SIGNATURE, FREAC3_01, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MYOD_Q6, GOBP_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_VITAMIN_A

GO Biological Process (11): retinoid metabolic process (GO:0001523), vitamin A metabolic process (GO:0006776), visual perception (GO:0007601), response to bacterium (GO:0009617), lipid storage (GO:0019915), positive regulation of lipid transport (GO:0032370), response to retinoic acid (GO:0032526), response to vitamin A (GO:0033189), retinol metabolic process (GO:0042572), cellular response to leukemia inhibitory factor (GO:1990830), lipid metabolic process (GO:0006629)

GO Molecular Function (8): retinoic acid binding (GO:0001972), O-palmitoyltransferase activity (GO:0016416), acyltransferase activity (GO:0016746), retinol binding (GO:0019841), phosphatidylcholine-retinol O-acyltransferase activity (GO:0047173), protein binding (GO:0005515), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740)

GO Cellular Component (8): multivesicular body (GO:0005771), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), rough endoplasmic reticulum (GO:0005791), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Visual phototransduction	2
Metabolism of fat-soluble vitamins	1
Retinoid cycle disease events	1
Metabolism	1
Sensory Perception	1
Diseases associated with visual transduction	1
Diseases of the neuronal system	1
Metabolism of vitamins and cofactors	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
retinoid metabolic process	2
response to lipid	2
retinoid binding	2
cytoplasm	2
endomembrane system	2
diterpenoid metabolic process	1
sensory perception of light stimulus	1
response to other organism	1
nutrient storage	1
lipid transport	1
regulation of lipid transport	1
positive regulation of transport	1
positive regulation of lipid localization	1
response to oxygen-containing compound	1
response to vitamin	1
primary alcohol metabolic process	1
hormone metabolic process	1
olefinic compound metabolic process	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
primary metabolic process	1
monocarboxylic acid binding	1
palmitoyltransferase activity	1
transferase activity	1
vitamin binding	1
alcohol binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
catalytic activity	1
late endosome	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum	1
intracellular anatomical structure	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRAT	RPE65	Q16518	976
LRAT	SPATA7	Q9P0W8	902
LRAT	TULP1	O00294	894
LRAT	AIPL1	Q9NZN9	888
LRAT	RDH12	Q96NR8	883
LRAT	STRA6	Q9BX79	850
LRAT	RD3	Q7Z3Z2	839
LRAT	GNAT1	P11488	833
LRAT	GUCY2D	Q02846	823
LRAT	RBP1	P09455	814
LRAT	IMPDH1	P20839	808
LRAT	RPGRIP1	Q96KN7	806
LRAT	LCA5	Q86VQ0	798
LRAT	MERTK	Q12866	797
LRAT	OPN4	Q9UHM6	782

IntAct

15 interactions, top by confidence:

A	B	Type	Score
LRAT	NME2P1	psi-mi:“MI:0915”(physical association)	0.590
LRAT	TMX2	psi-mi:“MI:0915”(physical association)	0.560
LRAT	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
	LRAT	psi-mi:“MI:0915”(physical association)	0.560
LRAT	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
LRAT		psi-mi:“MI:0915”(physical association)	0.000
LRAT	BLCAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): NME2P1 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), BLCAP (Two-hybrid), HSD17B13 (Two-hybrid), TMEM31 (Two-hybrid), TMX2 (Two-hybrid), LRAT (Reconstituted Complex), NME2P1 (Affinity Capture-MS), LRAT (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IMY7, A0A0R4IY06, A0JPF9, A2AP18, A5PJN5, C0IN03, D2KX21, E1BVR9, E9PYK3, F1ND48, O00534, O75038, O94952, O95237, P0C1Q3, P53817, Q1LWG4, Q1LZ50, Q32PY6, Q4R3W5, Q4R6L3, Q5M7X9, Q5R5S1, Q5RJG7, Q5S6T3, Q5T8I9, Q6DC39, Q75WE7, Q7Z5M8, Q7ZU92, Q8BYI6, Q8C0L6, Q8CAE2, Q8CAS9, Q8K3R3, Q8NHH9, Q8SPR7, Q8VDH1, Q90678, Q93V51

Diamond homologs: A0A0R4IY06, D2KX21, O95237, P53816, P53817, Q4KLN5, Q5R611, Q8R3U1, Q96KN8, Q9BGL2, Q9CPX5, Q9HDD0, Q9JI60, Q9JI61, Q9NWW9, Q9QZU4, Q9UL19, Q96KN1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
LRAT	“down-regulates quantity”	retinol	“chemical modification”
LRAT	“up-regulates quantity”	“all-trans-retinyl ester”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	9
Uncertain significance	152
Likely benign	73
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073195	NM_004744.5(LRAT):c.12del (p.Met5fs)	Pathogenic
1172717	NM_004744.5(LRAT):c.504C>A (p.Cys168Ter)	Pathogenic
1180621	NM_004744.5(LRAT):c.157_159dup (p.Val53dup)	Pathogenic
1359044	NM_004744.5(LRAT):c.312del (p.Val105fs)	Pathogenic
143129	NM_004744.5(LRAT):c.163C>T (p.Arg55Trp)	Pathogenic
236451	NM_004744.5(LRAT):c.473G>A (p.Trp158Ter)	Pathogenic
2746775	NM_004744.5(LRAT):c.462C>A (p.Tyr154Ter)	Pathogenic
2759020	NM_004744.5(LRAT):c.99_100del (p.Asp33fs)	Pathogenic
2829724	NM_004744.5(LRAT):c.198del (p.Asp67fs)	Pathogenic
2858521	NM_004744.5(LRAT):c.163del (p.Arg55fs)	Pathogenic
2913774	NM_004744.5(LRAT):c.540+1G>A	Pathogenic
3003206	NM_004744.5(LRAT):c.427_428del (p.Arg143fs)	Pathogenic
3246733	NC_000004.11:g.(?155665479)(155670288_?)del	Pathogenic
3246734	NC_000004.11:g.(?155665479)(155666038_?)del	Pathogenic
3246735	NC_000004.11:g.(?155665577)(155668060_?)del	Pathogenic
3249470	NM_004744.5(LRAT):c.17dup (p.Glu7fs)	Pathogenic
3649032	NM_004744.5(LRAT):c.253dup (p.Met85fs)	Pathogenic
3702659	NM_004744.5(LRAT):c.105_108del (p.Arg36fs)	Pathogenic
4743381	NM_004744.5(LRAT):c.519del (p.Ile174fs)	Pathogenic
5334	NM_004744.5(LRAT):c.525T>A (p.Ser175Arg)	Pathogenic
5335	NM_004744.5(LRAT):c.400_401del (p.Lys134fs)	Pathogenic
95178	NM_004744.5(LRAT):c.588dup (p.Ala197fs)	Pathogenic
978446	NC_000004.12:g.(?154740841)(154749136_?)del	Pathogenic
978449	NM_004744.5(LRAT):c.554_555del (p.Val185fs)	Pathogenic
978974	NM_004744.5(LRAT):c.241_242del (p.Leu81fs)	Pathogenic
1493539	NM_004744.5(LRAT):c.608T>A (p.Leu203Ter)	Likely pathogenic
191324	NM_004744.5(LRAT):c.233_242del (p.Leu78fs)	Likely pathogenic
2506311	NM_004744.5(LRAT):c.40_41delinsTT (p.Glu14Leu)	Likely pathogenic
3249814	NM_004744.5(LRAT):c.571G>T (p.Asp191Tyr)	Likely pathogenic
3336592	NM_004744.5(LRAT):c.470T>C (p.Leu157Pro)	Likely pathogenic

SpliceAI

556 predictions. Top by Δscore:

Variant	Effect	Δscore
4:154748982:A:AG	acceptor_gain	1.0000
4:154748983:G:GA	acceptor_gain	1.0000
4:154748983:GTTTT:G	acceptor_gain	1.0000
4:154748327:C:CG	donor_gain	0.9900
4:154748983:GTTT:G	acceptor_gain	0.9900
4:154744862:ACAAG:A	donor_loss	0.9800
4:154744863:CAAG:C	donor_loss	0.9800
4:154744864:AAGG:A	donor_loss	0.9800
4:154744865:AGGT:A	donor_loss	0.9800
4:154744866:GGTA:G	donor_loss	0.9800
4:154744868:T:C	donor_loss	0.9800
4:154749457:A:AG	acceptor_gain	0.9800
4:154744833:A:G	donor_gain	0.9700
4:154748327:C:G	donor_gain	0.9700
4:154748976:T:G	acceptor_loss	0.9700
4:154748978:TTCCA:T	acceptor_loss	0.9700
4:154748979:TCCAG:T	acceptor_loss	0.9700
4:154748980:CCAGT:C	acceptor_loss	0.9700
4:154748981:CAGT:C	acceptor_loss	0.9700
4:154748982:AGTTT:A	acceptor_loss	0.9700
4:154748977:TTTCC:T	acceptor_loss	0.9600
4:154748983:GT:G	acceptor_gain	0.9500
4:154748983:GTT:G	acceptor_gain	0.9500
4:154741736:GCTAT:G	donor_gain	0.9400
4:154740899:G:T	donor_gain	0.9300
4:154748971:T:G	acceptor_loss	0.9300
4:154750892:A:T	acceptor_gain	0.9200
4:154744744:G:GT	donor_gain	0.9100
4:154740905:G:GT	donor_gain	0.9000
4:154750891:TAG:T	acceptor_gain	0.9000

AlphaMissense

1497 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:154744538:C:A	A71D	0.995
4:154744673:T:C	F116S	0.995
4:154744849:A:C	S175R	0.995
4:154744851:T:A	S175R	0.995
4:154744851:T:G	S175R	0.995
4:154744469:G:T	G48V	0.994
4:154744830:C:G	C168W	0.994
4:154744833:A:C	R169S	0.994
4:154744833:A:T	R169S	0.994
4:154744550:C:A	P75H	0.993
4:154744652:G:C	R109P	0.993
4:154744672:T:C	F116L	0.993
4:154744674:C:A	F116L	0.993
4:154744674:C:G	F116L	0.993
4:154744469:G:A	G48D	0.992
4:154744506:C:A	H60Q	0.992
4:154744506:C:G	H60Q	0.992
4:154744535:T:A	V70D	0.992
4:154744504:C:G	H60D	0.991
4:154744511:G:A	G62D	0.991
4:154744760:C:A	A145D	0.991
4:154744468:G:C	G48R	0.990
4:154744537:G:C	A71P	0.990
4:154744673:T:G	F116C	0.990
4:154744759:G:C	A145P	0.990
4:154744806:C:A	N160K	0.990
4:154744806:C:G	N160K	0.990
4:154744829:G:A	C168Y	0.990
4:154744624:G:C	G100R	0.989
4:154744816:T:C	F164L	0.989

dbSNP variants (sampled 300 via entrez): RS1000306204 (4:154741147 T>C), RS1000439272 (4:154747528 T>C), RS10006272 (4:154743124 A>C), RS1000871889 (4:154750668 T>C), RS1000915640 (4:154743266 A>C), RS1001191325 (4:154750312 T>C), RS1002109296 (4:154749376 G>A), RS1002535070 (4:154745303 G>A), RS1002804429 (4:154742996 C>A,G), RS1002884862 (4:154749509 C>A,T), RS10032835 (4:154739111 G>A), RS1003849683 (4:154739333 C>T), RS1004115826 (4:154752322 G>A), RS1004214159 (4:154744154 C>T), RS1004822916 (4:154752837 T>C)

Disease associations

OMIM: gene MIM:604863 | disease phenotypes: MIM:613341, MIM:268000, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis 14	Strong	Autosomal recessive
Leber congenital amaurosis	Strong	Autosomal recessive
severe early-childhood-onset retinal dystrophy	Supportive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	AR

Mondo (7): Leber congenital amaurosis 14 (MONDO:0013231), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis (MONDO:0018998), breast ductal adenocarcinoma (MONDO:0005590), Leber congenital amaurosis 1 (MONDO:0008764), severe early-childhood-onset retinal dystrophy (MONDO:0009549)

Orphanet (3): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
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: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:0000556	Retinal dystrophy
HP:0000563	Keratoconus
HP:0000577	Exotropia
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000654	Decreased light- and dark-adapted electroretinogram amplitude
HP:0000662	Nyctalopia
HP:0000729	Autistic behavior

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006018_1	Activated partial thromboplastin time	4.000000e-16
GCST010396_204	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C567636	Leber Congenital Amaurosis 14 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2202 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 217,461 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL184618	FRAMYCETIN	3	217,461

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Resveratrol	affects cotreatment, decreases expression	2
Ethanol	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
ferrous chloride	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Sunitinib	increases expression	1
Vehicle Emissions	decreases methylation	1
Clorgyline	increases expression	1
Copper	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	affects cotreatment, increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Vitamin A	affects cotreatment, increases uptake	1
Isotretinoin	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL707894	Binding	Compound tested in vitro for inhibition of translation using highly active Escherichia coli S30 and a plasmid containing a gene expressing truncated lecithin retinol acyltransferase	Synthesis of (+),(-)-neamine and their positional isomers as potential antibiotics. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

263 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)
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
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
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)