PLOD3

procollagen-lysine,2-oxoglutarate 5-dioxygenase 3, the group of Procollagen-lysine,2-oxoglutarate 5-dioxygenase family

Basic information

Region (hg38): 7:101205977-101218420

Links

ENSG00000106397 ∙ NCBI:8985 ∙ OMIM:603066 ∙ HGNC:9083 ∙ Uniprot:O60568 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• bone fragility with contractures, arterial rupture, and deafness (Moderate), mode of inheritance: AR
• bone fragility with contractures, arterial rupture, and deafness (Strong), mode of inheritance: AR
• bone fragility with contractures, arterial rupture, and deafness (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bone fragility with contractures, arterial rupture, and deafness (BCARD syndrome)	AR	Audiologic/Otolaryngologic; Cardiovascular	The condition may be clinically recognizable in most individuals, but recognition may allow surveillance for and prompt treatment of vascular anomalies; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic	18834968

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLOD3 gene.

• not_provided (640 variants)
• Inborn_genetic_diseases (127 variants)
• PLOD3-related_disorder (30 variants)
• Bone_fragility_with_contractures,_arterial_rupture,_and_deafness (27 variants)
• not_specified (7 variants)
• Hemorrhage,_intracerebral,_susceptibility_to (3 variants)
• Neurodevelopmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLOD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001084.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	176	13	192
missense		3	254	39	4	300
nonsense	6	2				8
start loss						0
frameshift	13	1	3			17
splice donor/acceptor (+/-2bp)	1	12	2			15
Total	20	18	262	215	17

Highest pathogenic variant AF is 0.000041727948

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLOD3	protein_coding	protein_coding	ENST00000223127	19	12444

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.158	454	464	0.979	0.0000324	4743
Missense in Polyphen		92	106.17	0.86657		1077
Synonymous	-0.323	202	196	1.03	0.0000144	1476
Loss of Function	2.54	27	45.4	0.594	0.00000249	459

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000963	0.000958
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.000188	0.000185
European (Non-Finnish)	0.000301	0.000299
Middle Eastern	0.000435	0.000435
South Asian	0.000229	0.000229
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links. {ECO:0000250|UniProtKB:P24802}.
• Disease: DISEASE: Lysyl hydroxylase 3 deficiency (LH3 deficiency) [MIM:612394]: Connective tissue disorder. The syndrome is characterized by congenital malformations severely affecting many tissues and organs and revealing features of several collagen disorders, most of them involving COL2A1 (type II collagen). The findings suggest that the failure of lysyl hydroxylation and hydroxylysyl carbohydrate addition, which affects many collagens, is the molecular basis of this syndrome. {ECO:0000269|PubMed:18834968}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysine degradation - Homo sapiens (human);Other types of O-glycan biosynthesis - Homo sapiens (human);Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization (Consensus)

Recessive Scores

• pRec: 0.342

Intolerance Scores

• loftool: 0.242
• rvis_EVS: -1.12
• rvis_percentile_EVS: 6.58

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.652

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: plod3
• Affected structure: CaP motoneuron
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: in utero embryonic development;endothelial cell morphogenesis;protein O-linked glycosylation;protein localization;peptidyl-lysine hydroxylation;neural tube development;collagen fibril organization;cellular response to hormone stimulus;collagen metabolic process;vasodilation;hydroxylysine biosynthetic process;epidermis morphogenesis;oxidation-reduction process;lung morphogenesis;basement membrane assembly
• Cellular component: extracellular space;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;rough endoplasmic reticulum;Golgi apparatus;trans-Golgi network;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: iron ion binding;protein binding;procollagen-lysine 5-dioxygenase activity;L-ascorbic acid binding;procollagen glucosyltransferase activity;procollagen galactosyltransferase activity