LCAT

lecithin-cholesterol acyltransferase

Basic information

Region (hg38): 16:67939749-67944131

Links

ENSG00000213398 ∙ NCBI:3931 ∙ OMIM:606967 ∙ HGNC:6522 ∙ Uniprot:P04180 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the LCAT gene.

• Cardiovascular phenotype (104 variants)
• not provided (72 variants)
• LCAT deficiency (29 variants)
• Norum disease;Fish-eye disease (8 variants)
• Fish-eye disease;Norum disease (6 variants)
• Inborn genetic diseases (6 variants)
• Fish-eye disease (3 variants)
• Norum disease (3 variants)
• - (2 variants)
• not specified (1 variants)
• LCAT-related condition (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.

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			4	57	1	62
missense	6	5	59	9		79
nonsense	2					2
start loss						0
frameshift	2					2
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1				1
splice region			1	2		3
non coding			1	5	4	10
Total	10	6	66	71	5

Highest pathogenic variant AF is 0.0000394

Variants in LCAT

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

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

Position	Type	Phenotype	Significance	ClinVar
16-67939892-A-G		LCAT deficiency	Uncertain significance (Jun 14, 2016)
16-67939917-G-A		Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jun 27, 2022)
16-67939928-G-A			Likely benign (Sep 27, 2022)
16-67939933-C-T			Uncertain significance (Jul 31, 2022)
16-67939936-T-C		Cardiovascular phenotype	Likely benign (Oct 06, 2021)
16-67939937-C-T		Cardiovascular phenotype	Likely benign (Mar 18, 2023)
16-67939943-T-A		Cardiovascular phenotype	Likely benign (Jan 07, 2024)
16-67939960-G-A		Cardiovascular phenotype	Likely pathogenic (May 08, 2020)
16-67940001-A-G			Uncertain significance (Nov 19, 2021)
16-67940004-T-C		Cardiovascular phenotype	Uncertain significance (Nov 17, 2023)
16-67940017-T-C		LCAT deficiency	Pathogenic (Apr 29, 2019)
16-67940029-G-GT		LCAT deficiency	Pathogenic (Feb 01, 1993)
16-67940035-C-T		Fish-eye disease;Norum disease • Cardiovascular phenotype	Uncertain significance (Nov 05, 2021)
16-67940036-G-A		Cardiovascular phenotype • LCAT-related disorder	Likely benign (Nov 19, 2020)
16-67940039-C-T		Cardiovascular phenotype	Likely benign (Jan 27, 2024)
16-67940042-G-A		Cardiovascular phenotype	Likely benign (May 11, 2022)
16-67940045-C-A		Cardiovascular phenotype	Likely benign (Aug 16, 2022)
16-67940050-G-A		LCAT deficiency • Norum disease • Cardiovascular phenotype • Fish-eye disease	Benign (Jan 31, 2024)
16-67940054-C-T		LCAT deficiency	Uncertain significance (Jan 13, 2018)
16-67940064-G-A		Cardiovascular phenotype	Uncertain significance (Apr 28, 2023)
16-67940090-G-A		Cardiovascular phenotype	Likely benign (Dec 23, 2022)
16-67940095-C-T		Cardiovascular phenotype • LCAT-related disorder	Benign/Likely benign (Sep 06, 2023)
16-67940102-G-A		Cardiovascular phenotype	Likely benign (Dec 26, 2020)
16-67940108-C-T		Cardiovascular phenotype	Likely benign (Oct 19, 2023)
16-67940109-G-A		LCAT deficiency	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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