LRAT

lecithin retinol acyltransferase, the group of LRAT domain containing family

Basic information

Region (hg38): 4:154626945-154753120

Links

ENSG00000121207 ∙ NCBI:9227 ∙ OMIM:604863 ∙ HGNC:6685 ∙ Uniprot:O95237 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber congenital amaurosis 9 (Strong), mode of inheritance: AR
• 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 (Definitive), mode of inheritance: AR
• Leber congenital amaurosis 14 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the LRAT gene.

• not provided (15 variants)
• RETINAL DYSTROPHY, EARLY-ONSET SEVERE, LRAT-RELATED (2 variants)
• Leber congenital amaurosis 14 (2 variants)
• Retinitis pigmentosa (1 variants)
• Retinal dystrophy (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	60	1	62
missense	2	2	69	1	2	76
nonsense	3	3				6
start loss						0
frameshift	9	3	1			13
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)	1					1
splice region			1			1
non coding			69	11		80
Total	16	8	142	72	3

Highest pathogenic variant AF is 0.00000658

Variants in LRAT

This is a list of pathogenic ClinVar variants found in the LRAT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-154744025-G-T		Retinitis pigmentosa	Likely benign (Apr 27, 2017)
4-154744109-C-G		Leber congenital amaurosis • Retinitis pigmentosa • Leber congenital amaurosis 14	Uncertain significance (Jan 13, 2018)
4-154744140-C-T		Leber congenital amaurosis 14 • Retinitis pigmentosa • Retinal dystrophy	Uncertain significance (Jan 12, 2018)
4-154744209-C-T		Leber congenital amaurosis 14 • Retinitis pigmentosa	Uncertain significance (Apr 27, 2017)
4-154744229-A-C		Retinitis pigmentosa • Leber congenital amaurosis 14 • Leber congenital amaurosis	Uncertain significance (Jan 13, 2018)
4-154744314-T-C		Retinitis pigmentosa	Uncertain significance (Apr 27, 2017)
4-154744334-A-G			Benign (Jan 18, 2024)
4-154744334-AC-A			Pathogenic (Jun 16, 2017)
4-154744335-C-T			Likely benign (Nov 02, 2023)
4-154744337-C-A			Uncertain significance (Aug 14, 2021)
4-154744347-G-A			Likely benign (May 24, 2022)
4-154744352-T-C			Uncertain significance (Oct 13, 2022)
4-154744353-G-A			Likely benign (Dec 28, 2023)
4-154744357-T-C			Likely benign (Aug 02, 2023)
4-154744366-G-T		Leber congenital amaurosis	Likely pathogenic (Dec 27, 2018)
4-154744366-GA-TT		Leber congenital amaurosis	Likely pathogenic (May 30, 2023)
4-154744372-C-A			Uncertain significance (Jun 10, 2022)
4-154744374-GCTC-G			Uncertain significance (Apr 15, 2022)
4-154744392-C-T			Likely benign (May 05, 2022)
4-154744395-G-A			Likely benign (Aug 02, 2023)
4-154744398-C-T			Likely benign (Jun 16, 2023)
4-154744400-T-A		Leber congenital amaurosis 14 • not specified • Retinitis pigmentosa	Benign/Likely benign (Jan 30, 2024)
4-154744404-T-A		Breast ductal adenocarcinoma	Uncertain significance (Jul 20, 2015)
4-154744406-C-G		Retinitis pigmentosa • Inborn genetic diseases • Leber congenital amaurosis 14	Uncertain significance (Apr 19, 2022)
4-154744407-G-T			Likely benign (Mar 26, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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