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

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 (51 variants)
• not provided (6 variants)
• LIPOPROTEIN(a) POLYMORPHISM (3 variants)
• Lipoprotein(a) deficiency, congenital (2 variants)
• not specified (1 variants)
• Abnormal bleeding;Thrombocytopenia (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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			48	3	5	56
nonsense	1		1			2
start loss						0
frameshift						0
inframe indel						0
splice variant			1	1	2	4
non coding					1	1
Total	1	0	50	4	8

Highest pathogenic variant AF is 0.0000197

Variants in LPA

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

Position	Type	Phenotype	Significance	ClinVar
6-160531748-C-T			Benign (Nov 01, 2022)
6-160531779-G-A		Inborn genetic diseases	Uncertain significance (Jan 18, 2022)
6-160531806-G-A			Benign (Apr 20, 2019)
6-160531871-A-G		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
6-160532649-C-T		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)
6-160537897-C-T		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
6-160540079-G-A		Inborn genetic diseases	Uncertain significance (Nov 09, 2021)
6-160540105-T-C		LIPOPROTEIN(a) POLYMORPHISM	Benign (Aug 07, 2020)
6-160540140-G-C		Inborn genetic diseases	Uncertain significance (May 05, 2023)
6-160540183-C-G		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
6-160541120-G-A		Inborn genetic diseases	Uncertain significance (Feb 17, 2022)
6-160542757-G-A		Inborn genetic diseases	Uncertain significance (Jul 11, 2023)
6-160542769-G-A		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
6-160545458-A-G		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
6-160545505-T-C		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
6-160545509-T-C		Inborn genetic diseases	Likely benign (Apr 13, 2022)
6-160545521-G-C		Inborn genetic diseases	Uncertain significance (Oct 22, 2021)
6-160547791-T-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
6-160547809-A-G		Inborn genetic diseases	Likely benign (Apr 12, 2022)
6-160547881-C-T		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
6-160547886-A-G		Inborn genetic diseases	Uncertain significance (Nov 22, 2022)
6-160547936-G-A		Myofibrillar myopathy 6	Benign/Likely benign (Dec 15, 2020)
6-160548507-A-T		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
6-160548552-G-C		Abnormal bleeding;Thrombocytopenia	Uncertain significance (May 01, 2020)
6-160548597-A-G			Benign (Oct 15, 2020)

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