PLOD1

procollagen-lysine,2-oxoglutarate 5-dioxygenase 1, the group of Procollagen-lysine,2-oxoglutarate 5-dioxygenase family

Basic information

Region (hg38): 1:11934204-11975538

Previous symbols: [ "LLH", "PLOD" ]

Links

ENSG00000083444 ∙ NCBI:5351 ∙ OMIM:153454 ∙ HGNC:9081 ∙ Uniprot:Q02809 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ehlers-Danlos syndrome, kyphoscoliotic type 1 (Definitive), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic type 1 (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic type 1 (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic type 1 (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic type 1 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, kyphoscoliotic type, 1	AR	Cardiovascular; Ophthalmologic; Renal	EDS VI may be clinically recognizable, but care may be considered related to issues such as potential severe vascular rupture (beneficial preventive measures include blood pressure management); Adequate hydration to prevent nephroliathisis may be beneficial; Though not frequent, individuals may demonstrate ophthalmologic sequelae (eg, glaucoma), and appropriate surveillance and preventive measures may be beneficial	Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic; Renal	4342967; 5027136; 5016372; 4373475; 1184396; 429005; 2504907; 8449506; 7977351; 8574422; 9152832; 9220536; 9557891; 9686670; 15666309; 15979919; 16329110; 17100196; 19320026; 20301635; 22001912

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLOD1 gene.

• Ehlers-Danlos syndrome, kyphoscoliotic type 1 (701 variants)
• Familial thoracic aortic aneurysm and aortic dissection (328 variants)
• not provided (232 variants)
• not specified (70 variants)
• Ehlers-Danlos syndrome (36 variants)
• Inborn genetic diseases (16 variants)
• PLOD1-related condition (3 variants)
• 6 conditions (2 variants)
• Keratoconus (1 variants)
• 8 conditions (1 variants)
• Increased circulating IgA level (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLOD1 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				196	7	203
missense		3	332	11	2	348
nonsense	16	2	3			21
start loss			1			1
frameshift	17	3	3			23
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	3	15	1			19
splice region		1	20	24	1	46
non coding			23	145	47	215
Total	36	24	367	352	56

Highest pathogenic variant AF is 0.0000394

Variants in PLOD1

This is a list of pathogenic ClinVar variants found in the PLOD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-11934495-G-A			Benign (Jun 28, 2018)
1-11934559-G-C			Benign (Jun 26, 2018)
1-11934630-T-C			Benign (Sep 07, 2018)
1-11934703-G-A		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Conflicting classifications of pathogenicity (Jul 01, 2023)
1-11934716-C-G		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Uncertain significance (Jun 14, 2016)
1-11934719-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Uncertain significance (Jan 12, 2018)
1-11934722-G-A		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Uncertain significance (Jan 13, 2018)
1-11934741-G-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Uncertain significance (Jan 12, 2018)
1-11934751-GT-G		not specified	Likely benign (Sep 07, 2017)
1-11934753-C-A		not specified	Likely benign (Oct 06, 2017)
1-11934761-C-T		not specified	Uncertain significance (Jul 21, 2023)
1-11934766-CCCATACCTCGG-C		Familial thoracic aortic aneurysm and aortic dissection • Ehlers-Danlos syndrome, kyphoscoliotic type 1	Uncertain significance (May 08, 2023)
1-11934783-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1 • Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 05, 2023)
1-11934788-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Likely benign (Jan 28, 2024)
1-11934789-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Likely benign (Dec 16, 2023)
1-11934804-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Likely benign (Oct 24, 2023)
1-11934809-G-A		Ehlers-Danlos syndrome, kyphoscoliotic type 1 • Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Nov 06, 2023)
1-11934809-G-C		Ehlers-Danlos syndrome, kyphoscoliotic type 1 • Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Aug 02, 2023)
1-11934812-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Likely benign (Oct 09, 2021)
1-11934813-T-C			Uncertain significance (Apr 08, 2022)
1-11934827-C-T		Familial thoracic aortic aneurysm and aortic dissection • Ehlers-Danlos syndrome, kyphoscoliotic type 1	Likely benign (Dec 15, 2023)
1-11934831-G-A		Ehlers-Danlos syndrome, kyphoscoliotic type 1 • Familial thoracic aortic aneurysm and aortic dissection • not specified	Uncertain significance (Aug 09, 2023)
1-11934833-G-A		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Likely benign (Nov 29, 2023)
1-11934836-G-A		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Jun 02, 2020)
1-11934839-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type 1	Likely benign (Dec 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLOD1	protein_coding	protein_coding	ENST00000196061	19	41334

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.48e-15	0.733	125690	0	58	125748	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.394	423	446	0.948	0.0000306	4752
Missense in Polyphen		111	118.16	0.93939		1226
Synonymous	-0.478	198	190	1.04	0.0000136	1421
Loss of Function	1.88	30	43.4	0.692	0.00000245	452

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.000328	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000321	0.000316
Middle Eastern	0.000328	0.000326
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (By similarity). Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:8621606, PubMed:10686424, PubMed:15854030). These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links (Probable). {ECO:0000250|UniProtKB:Q9R0E2, ECO:0000269|PubMed:10686424, ECO:0000269|PubMed:15854030, ECO:0000269|PubMed:8621606, ECO:0000305}.
• Disease: DISEASE: Ehlers-Danlos syndrome, kyphoscoliotic type, 1 (EDSKSCL1) [MIM:225400]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSKSCL1 is an autosomal recessive form characterized by severe muscle hypotonia at birth, generalized joint laxity, scoliosis at birth, and scleral fragility and rupture of the ocular globe. {ECO:0000269|PubMed:10686424, ECO:0000269|PubMed:15666309, ECO:0000269|PubMed:15854030, ECO:0000269|PubMed:15979919, ECO:0000269|PubMed:8163671, ECO:0000269|PubMed:9617436}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysine degradation - Homo sapiens (human);Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization (Consensus)

Intolerance Scores

• loftool: 0.378
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.09

Haploinsufficiency Scores

• pHI: 0.253
• hipred: N
• hipred_score: 0.414
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.666

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plod1
• Phenotype: muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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)

Zebrafish Information Network

• Gene name: plod1a
• Affected structure: actinotrichium
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: response to hypoxia;cellular protein modification process;protein O-linked glycosylation;epidermis development;peptidyl-lysine hydroxylation;collagen fibril organization;collagen metabolic process;hydroxylysine biosynthetic process;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane;rough endoplasmic reticulum membrane;extracellular exosome;catalytic complex
• Molecular function: iron ion binding;procollagen-lysine 5-dioxygenase activity;L-ascorbic acid binding;procollagen glucosyltransferase activity;protein homodimerization activity