LRAT
lecithin retinol acyltransferase, the group of LRAT domain containing family
Basic information
Region (hg38): 4:154626945-154753120
Links
Phenotypes
GenCC
Source:
- Leber congenital amaurosis 14 (Moderate), mode of inheritance: AR
- retinitis pigmentosa (Supportive), mode of inheritance: AD
- Leber congenital amaurosis (Supportive), mode of inheritance: AD
- severe early-childhood-onset retinal dystrophy (Supportive), mode of inheritance: AR
- Leber congenital amaurosis 14 (Strong), mode of inheritance: AR
- Leber congenital amaurosis 14 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Leber congenital amaurosis 14; Retinitis pigmentosa, juvenile; Retinal-dystrophy, early-onset severe; Retinitis punctata albescens | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Ophthalmologic | 11381255; 17011878; 18055821; 22559933; 22570351 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (166 variants)
- Leber_congenital_amaurosis_14 (32 variants)
- Inborn_genetic_diseases (21 variants)
- Retinitis_pigmentosa (21 variants)
- Retinal_dystrophy (14 variants)
- Leber_congenital_amaurosis (9 variants)
- LRAT-related_disorder (5 variants)
- not_specified (5 variants)
- Leber_congenital_amaurosis_1 (3 variants)
- RETINAL_DYSTROPHY,_EARLY-ONSET_SEVERE,_LRAT-RELATED (2 variants)
- Autosomal_recessive_retinitis_pigmentosa (2 variants)
- RETINITIS_PIGMENTOSA,_JUVENILE,_LRAT-RELATED (1 variants)
- Breast_ductal_adenocarcinoma (1 variants)
- Abnormality_of_the_eye (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRAT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004744.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 65 | 66 | ||||
| missense | 11 | 82 | 99 | |||
| nonsense | 6 | |||||
| start loss | 0 | |||||
| frameshift | 13 | 19 | ||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 19 | 18 | 84 | 68 | 2 |
Highest pathogenic variant AF is 0.0000303609
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LRAT | protein_coding | protein_coding | ENST00000336356 | 2 | 126174 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0284 | 0.813 | 125734 | 0 | 14 | 125748 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.0206 | 127 | 126 | 1.01 | 0.00000616 | 1496 |
| Missense in Polyphen | 35 | 44.371 | 0.7888 | 546 | ||
| Synonymous | -0.246 | 57 | 54.7 | 1.04 | 0.00000269 | 492 |
| Loss of Function | 1.08 | 3 | 5.81 | 0.517 | 2.51e-7 | 76 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000177 | 0.000177 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000704 | 0.0000703 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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. {ECO:0000269|PubMed:9920938}.;
- Disease
- DISEASE: 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. {ECO:0000269|PubMed:11381255, ECO:0000269|PubMed:17011878, ECO:0000269|PubMed:18055821}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Retinol metabolism - Homo sapiens (human);Vitamin digestion and absorption - Homo sapiens (human);Vitamin A Deficiency;Retinol Metabolism;Vitamin A and Carotenoid Metabolism;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism;The canonical retinoid cycle in rods (twilight vision);Metabolism of vitamins and cofactors;Visual signal transduction: Rods;retinol biosynthesis;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;the visual cycle I (vertebrates);GPCR downstream signalling;Visual signal transduction: Cones
(Consensus)
Recessive Scores
- pRec
- 0.225
Intolerance Scores
- loftool
- 0.579
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 56.64
Haploinsufficiency Scores
- pHI
- 0.0956
- hipred
- Y
- hipred_score
- 0.521
- ghis
- 0.514
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.202
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lrat
- Phenotype
- vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- lratb.1
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- retinoid metabolic process;vitamin A metabolic process;visual perception;response to bacterium;positive regulation of lipid transport;response to retinoic acid;response to vitamin A;retinol metabolic process;cellular response to leukemia inhibitory factor
- Cellular component
- multivesicular body;endoplasmic reticulum membrane;rough endoplasmic reticulum;integral component of membrane;perinuclear region of cytoplasm
- Molecular function
- retinoic acid binding;O-palmitoyltransferase activity;transferase activity, transferring acyl groups;retinol binding;phosphatidylcholine-retinol O-acyltransferase activity;lecithin:11-cis retinol acyltransferase activity