PLOD3

Chr 7AR

procollagen-lysine,2-oxoglutarate 5-dioxygenase 3

Also known as: BCARD, LH3

NCBI Gene: 8985ENSG00000106397UniProt: O60568

The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

BCARD syndrome (lysyl hydroxylase 3 deficiency)MIM #612394
AR
581
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PLOD3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 194 VUS of 581 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.82LOEUF
pLI 0.000
Z-score 2.54
OE 0.59 (0.44–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.16Z-score
OE missense 0.98 (0.91–1.06)
454 obs / 463.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.44–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 27 / 45.4Missense obs/exp: 454 / 463.5Syn Z: -0.32

ClinVar Variant Classifications

581 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic17
VUS194
Likely Benign297
Benign32
Conflicting15
26
Pathogenic
17
Likely Pathogenic
194
VUS
297
Likely Benign
32
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
17
0
26
Likely Pathogenic
12
1
4
0
17
VUS
1
172
19
2
194
Likely Benign
0
12
139
146
297
Benign
0
4
16
12
32
Conflicting
—15
Total22189195160581

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PLOD3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PLOD3-related lysyl hydroxylase 3 deficiency

limited
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

BCARD syndrome (lysyl hydroxylase 3 deficiency)

MIM #612394

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
Pathogenic variants in PLOD3 result in a Stickler syndrome-like connective tissue disorder with vascular complications.
Ewans LJ et al.·J Med Genet
2019Review
Analysis of genetic profiling, pathomics signature, and prognostic features of primary lymphoepithelioma-like carcinoma of the renal pelvis.
Fan B et al.·Mol Oncol
2022
Integrative analysis regarding the correlation between collagen-related genes and prostate cancer.
Xiao Y et al.·BMC Cancer
2024
PLOD3 Is Associated with Immune Cell Infiltration and Genomic Instability in Colon Adenocarcinoma.
Deng X et al.·Biomed Res Int
2021
PLOD3 is Upregulated in Gastric Cancer and Correlated with Clinicopathologic Characteristics.
Wang B et al.·Clin Lab
2019
Multicenter phase II trial of Camrelizumab combined with Apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer.
Liu J et al.·Nat Commun
2022Clinical trial
Pathomechanisms of epidermolysis bullosa: Beyond structural proteins.
Harvey N et al.·Matrix Biol
2022Review
New mechanistic insights to PLOD1-mediated human vascular disease.
Koenig SN et al.·Transl Res
2022
Oncogenic role of PLOD3 mediated by SOX9 through IL-6/JAK/STAT3 pathway in cervical cancer.
Li J et al.·Cell Signal
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools