PLOD2

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

Basic information

Region (hg38): 3:146035139-146163725

Links

ENSG00000152952 ∙ NCBI:5352 ∙ OMIM:601865 ∙ HGNC:9082 ∙ Uniprot:O00469 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bruck syndrome 2 (Definitive), mode of inheritance: AR
• Bruck syndrome 2 (Strong), mode of inheritance: AR
• Bruck syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bruck syndrome 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	12881513; 15523624; 22689593

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLOD2 gene.

• not_provided (295 variants)
• Inborn_genetic_diseases (81 variants)
• Bruck_syndrome_2 (63 variants)
• not_specified (27 variants)
• Osteogenesis_imperfecta (21 variants)
• PLOD2-related_disorder (15 variants)
• Short_femur (2 variants)
• Camptodactyly (2 variants)
• Cleft_soft_palate (2 variants)
• Clubfoot (2 variants)
• Radial_bowing (2 variants)
• Bowing_of_the_long_bones (2 variants)
• Ulnar_bowing (2 variants)
• Femoral_bowing (2 variants)
• Aplasia/hypoplasia_of_the_femur (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLOD2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000182943.3. 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			6	48		54
missense	3	7	175	14	1	200
nonsense	6	6	1			13
start loss						0
frameshift	6	5				11
splice donor/acceptor (+/-2bp)	1	6				7
Total	16	24	182	62	1

Highest pathogenic variant AF is 0.000092982

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLOD2	protein_coding	protein_coding	ENST00000282903	20	94214

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.70e-8	1.00	125653	0	91	125744	0.000362

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.561	369	401	0.921	0.0000199	5010
Missense in Polyphen		113	127.03	0.88958		1571
Synonymous	-0.432	142	136	1.05	0.00000654	1369
Loss of Function	3.51	20	45.6	0.439	0.00000246	543

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000364	0.000362
Ashkenazi Jewish	0.000109	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00195	0.00194
European (Non-Finnish)	0.000239	0.000237
Middle Eastern	0.000163	0.000163
South Asian	0.000263	0.000261
Other	0.000327	0.000326

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: Note=PLOD2 mutations give rise to a broad variety of phenotypes with variable degrees of severity of bone fragility and joint contractures. Disease-associated mutations have been found in patients with autosomal recessive osteogenesis imperfecta (AR- OI) (PubMed:22689593). {ECO:0000269|PubMed:22689593}.
• Pathway: Lysine degradation - Homo sapiens (human);Pathways in clear cell renal cell carcinoma;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.185
• rvis_EVS: 0.11
• rvis_percentile_EVS: 62.1

Haploinsufficiency Scores

• pHI: 0.650
• hipred: Y
• hipred_score: 0.591
• ghis: 0.478

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• 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	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Plod2

Zebrafish Information Network

• Gene name: plod2
• Affected structure: bone tissue
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

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