LCAT
lecithin-cholesterol acyltransferase
Basic information
Region (hg38): 16:67939750-67944131
Links
Phenotypes
GenCC
Source:
- fish eye disease (Supportive), mode of inheritance: AR
- Norum disease (Supportive), mode of inheritance: AR
- LCAT deficiency (Definitive), mode of inheritance: AR
- fish eye disease (Definitive), mode of inheritance: AR
- fish eye disease (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Lecithin:cholesterol acyltransferase deficiency (Norum disease); Fish-eye disease | AR | Cardiovascular; Renal | Dietary measures (eg, reducing fat intake) may be beneficial in controlling LDL and decreasing sequelae; In LCAT deficiency, medical treatment related to renal disease (eg, with ACE inhibitors) may preserve renal function, though renal transplant may be required | Biochemical; Cardiovascular; Hematologic; Ophthalmologic; Renal | 5704704; 408950; 7156322; 7148518; 6624548; 6695915; 3661502; 1898657; 2370048; 2052566; 9180249; 9884427; 18042612; 21901787; 22108153; 22189200; 22701329; 23043194; 23391322; 23412821; 23522979 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cardiovascular_phenotype (181 variants)
- not_provided (112 variants)
- Norum_disease (72 variants)
- Fish-eye_disease (71 variants)
- LCAT_deficiency (34 variants)
- LCAT-related_disorder (6 variants)
- not_specified (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LCAT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000229.2. 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 | 101 | 103 | ||||
| missense | 12 | 11 | 124 | 14 | 161 | |
| nonsense | 7 | |||||
| start loss | 0 | |||||
| frameshift | 7 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 16 | 22 | 127 | 115 | 0 |
Highest pathogenic variant AF is 0.0000620054
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LCAT | protein_coding | protein_coding | ENST00000264005 | 6 | 4382 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0810 | 0.917 | 125730 | 0 | 14 | 125744 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 203 | 263 | 0.770 | 0.0000181 | 2845 |
| Missense in Polyphen | 44 | 63.617 | 0.69163 | 694 | ||
| Synonymous | -0.0346 | 113 | 113 | 1.00 | 0.00000783 | 913 |
| Loss of Function | 2.71 | 5 | 17.1 | 0.292 | 7.57e-7 | 184 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000882 | 0.0000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs) (PubMed:10329423, PubMed:19065001, PubMed:26195816). The cholesterol ester is then transported back to the liver. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines (PubMed:8820107). Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE- containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms (PubMed:10722751). {ECO:0000269|PubMed:10329423, ECO:0000269|PubMed:10722751, ECO:0000269|PubMed:14636062, ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:26195816, ECO:0000269|PubMed:8820107}.;
- Disease
- DISEASE: Lecithin-cholesterol acyltransferase deficiency (LCATD) [MIM:245900]: A disorder of lipoprotein metabolism characterized by inadequate esterification of plasmatic cholesterol. Two clinical forms are recognized: complete LCAT deficiency and fish- eye disease. LCATD is generally referred to the complete form which is associated with absence of both alpha and beta LCAT activities resulting in esterification anomalies involving both HDL (alpha-LCAT activity) and LDL (beta-LCAT activity). It causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure. {ECO:0000269|PubMed:11423760, ECO:0000269|PubMed:12957688, ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:16051254, ECO:0000269|PubMed:16216249, ECO:0000269|PubMed:1681161, ECO:0000269|PubMed:1859405, ECO:0000269|PubMed:2370048, ECO:0000269|PubMed:7607641, ECO:0000269|PubMed:7711728, ECO:0000269|PubMed:8318557, ECO:0000269|PubMed:8432868, ECO:0000269|PubMed:8807342, ECO:0000269|PubMed:9007616, ECO:0000269|PubMed:9741700}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Fish-eye disease (FED) [MIM:136120]: A disorder of lipoprotein metabolism due to partial lecithin-cholesterol acyltransferase deficiency that affects only alpha-LCAT activity. FED is characterized by low plasma HDL and corneal opacities due to accumulation of cholesterol deposits in the cornea ('fish- eye'). {ECO:0000269|PubMed:1516702, ECO:0000269|PubMed:1571050, ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:1737840, ECO:0000269|PubMed:21901787, ECO:0000269|PubMed:8620346, ECO:0000269|PubMed:9261271}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Glycerophospholipid metabolism - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Composition of Lipid Particles;Statin Pathway;HDL remodeling;Transport of small molecules;Glycerophospholipid metabolism;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling
(Consensus)
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- loftool
- 0.127
- rvis_EVS
- -0.29
- rvis_percentile_EVS
- 32.94
Haploinsufficiency Scores
- pHI
- 0.125
- hipred
- Y
- hipred_score
- 0.613
- ghis
- 0.559
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lcat
- Phenotype
- endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; liver/biliary system phenotype; renal/urinary system phenotype;
Gene ontology
- Biological process
- phospholipid metabolic process;phosphatidylcholine biosynthetic process;cholesterol metabolic process;cholesterol transport;very-low-density lipoprotein particle remodeling;high-density lipoprotein particle remodeling;cholesterol esterification;lipoprotein biosynthetic process;cholesterol homeostasis;reverse cholesterol transport;phosphatidylcholine metabolic process;regulation of high-density lipoprotein particle assembly
- Cellular component
- extracellular region;extracellular space;high-density lipoprotein particle;extracellular exosome
- Molecular function
- phosphatidylcholine-sterol O-acyltransferase activity;protein binding;apolipoprotein A-I binding