LPA

lipoprotein(a)

Basic information

Region (hg38): 6:160531481-160664275

Previous symbols: [ "LP" ]

Links

ENSG00000198670 ∙ NCBI:4018 ∙ OMIM:152200 ∙ HGNC:6667 ∙ Uniprot:P08519 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipoprotein A deficiency, congenital	AR	General	The clinical relevance of the condition is unclear	General	7726859; 10484779; 15523644; 16840570; 16267501; 20032323

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LPA gene.

• Inborn genetic diseases (79 variants)
• not provided (18 variants)
• not specified (1 variants)
• LIPOPROTEIN(a) POLYMORPHISM (1 variants)
• Lipoprotein(a) deficiency, congenital (1 variants)
• Myofibrillar myopathy 6 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LPA 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				2		2
missense			76	9	5	90
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1		2	3
splice region				3		3
non coding						0
Total	0	0	77	11	7

Variants in LPA

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

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

Position	Type	Phenotype	Significance	ClinVar
6-160531748-C-T			Benign (Nov 01, 2022)
6-160531779-G-A		not specified	Uncertain significance (Jan 18, 2022)
6-160531806-G-A			Benign (Apr 20, 2019)
6-160531871-A-G		not specified	Uncertain significance (Aug 08, 2023)
6-160532649-C-T		not specified	Uncertain significance (Jan 11, 2023)
6-160537897-C-T		not specified	Uncertain significance (Sep 01, 2021)
6-160540037-G-A			Likely benign (Feb 01, 2023)
6-160540079-G-A		not specified	Uncertain significance (Nov 09, 2021)
6-160540103-T-C		not specified	Uncertain significance (Nov 06, 2023)
6-160540105-T-C		LIPOPROTEIN(a) POLYMORPHISM	Benign (Aug 07, 2020)
6-160540140-G-C		not specified	Uncertain significance (May 05, 2023)
6-160540183-C-G		not specified	Uncertain significance (Jan 26, 2022)
6-160541120-G-A		not specified	Uncertain significance (Feb 17, 2022)
6-160541153-A-G			Likely benign (Feb 01, 2023)
6-160541179-A-G		not specified	Uncertain significance (Dec 14, 2023)
6-160542742-C-T			Uncertain significance (Nov 01, 2023)
6-160542757-G-A		not specified	Uncertain significance (Jul 11, 2023)
6-160542769-G-A		not specified	Uncertain significance (Jul 06, 2021)
6-160545458-A-G		not specified	Uncertain significance (Mar 14, 2023)
6-160545505-T-C		not specified	Uncertain significance (Sep 16, 2021)
6-160545509-T-C		not specified	Likely benign (Apr 13, 2022)
6-160545521-G-C		not specified	Uncertain significance (Oct 22, 2021)
6-160545527-G-A			Likely benign (Nov 01, 2023)
6-160547791-T-A		not specified	Uncertain significance (Jan 23, 2023)
6-160547809-A-G		not specified	Likely benign (Apr 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LPA	protein_coding	protein_coding	ENST00000447678	39	134893

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.59e-89	8.54e-19	114094	346	11308	125748	0.0475

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.27	1015	761	1.33	0.0000418	13062
Missense in Polyphen		481	333.06	1.4442		5596
Synonymous	-6.19	413	281	1.47	0.0000167	4017
Loss of Function	-2.71	118	90.2	1.31	0.00000562	1320

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.126	0.123
Ashkenazi Jewish	0.0290	0.0289
East Asian	0.00417	0.00403
Finnish	0.0780	0.0779
European (Non-Finnish)	0.0389	0.0386
Middle Eastern	0.00417	0.00403
South Asian	0.0470	0.0454
Other	0.0434	0.0429

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for megalin/Gp 330. {ECO:0000269|PubMed:2531657}.
• Pathway: Cholesterol metabolism - Homo sapiens (human);LDL remodeling;Transport of small molecules;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling;amb2 Integrin signaling (Consensus)

Haploinsufficiency Scores

• pHI: 0.0757
• hipred: N
• hipred_score: 0.335

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.678

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	Medium	High

Gene ontology

• Biological process: proteolysis;lipid metabolic process;lipid transport;blood circulation;negative regulation of endopeptidase activity;low-density lipoprotein particle remodeling
• Cellular component: extracellular region;plasma lipoprotein particle
• Molecular function: fibronectin binding;serine-type endopeptidase activity;endopeptidase inhibitor activity;protein binding;heparin binding;apolipoprotein binding