PLOD1

Chr 1

procollagen-lysine,2-oxoglutarate 5-dioxygenase 1

Also known as: EDS6, EDSKCL1, LH, LH1, LLH, PLOD

NCBI Gene: 5351ENSG00000083444UniProt: Q02809

Lysyl hydroxylase is a membrane-bound homodimeric protein localized to the cisternae of the 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 VI have deficiencies in lysyl hydroxylase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

Primary Disease Associations & Inheritance

UniProtEhlers-Danlos syndrome, kyphoscoliotic type, 1
577
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PLOD1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 208 VUS of 577 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.94LOEUF
pLI 0.000
Z-score 1.88
OE 0.69 (0.52–0.94)
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.
0.39Z-score
OE missense 0.95 (0.87–1.03)
423 obs / 446.4 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.0.69 (0.52–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.87–1.03)
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.1.04
0≤1.21.6
LoF obs/exp: 30 / 43.4Missense obs/exp: 423 / 446.4Syn Z: -0.48

ClinVar Variant Classifications

577 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic36
VUS208
Likely Benign263
Benign7
Conflicting26
37
Pathogenic
36
Likely Pathogenic
208
VUS
263
Likely Benign
7
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
27
0
37
Likely Pathogenic
28
1
7
0
36
VUS
1
177
26
4
208
Likely Benign
0
8
124
131
263
Benign
0
0
7
0
7
Conflicting
—26
Total38187191135577

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

View in ClinVar →

Protein Context — Lollipop Plot

PLOD1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PLOD1-related Ehlers-Danlos syndrome, kyphoscoliotic type

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkin
G2P ↗

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — PLOD1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer.
Chi M et al.·J Exp Clin Cancer Res
2022
P3H4 and PLOD1 expression associates with poor prognosis in bladder cancer.
Zhang J et al.·Clin Transl Oncol
2022Meta-analysis
New mechanistic insights to PLOD1-mediated human vascular disease.
Koenig SN et al.·Transl Res
2022
PLOD1 acts as a tumor promoter in glioma via activation of the HSF1 signaling pathway.
Yuan B et al.·Mol Cell Biochem
2022
High Expression of PLOD1 Drives Tumorigenesis and Affects Clinical Outcome in Gastrointestinal Carcinoma.
Wang D et al.·Genet Test Mol Biomarkers
2018
Gluconic acid alleviates hypertrophic scar formation through binding PLOD1, reducing p-AKT signaling and activating autophagy.
Li J et al.·Phytomedicine
2025
Hypoxia-induced PLOD1 overexpression contributes to the malignant phenotype of glioblastoma via NF-κB signaling.
Wang Z et al.·Oncogene
2021
A clinical study showing the expression characteristics of cuproptosis markers in cases with Wilson disease.
Tao Z et al.·Medicine (Baltimore)
2024Cohort
Whole Blood Multi-OMIC Analysis Is Effective in Clinical Interpretation of Splicing Aberrations in PLOD1 -Related Kyphoscoliotic Ehlers-Danlos Syndrome.
Russo F et al.·Am J Med Genet A
2025Case report
Characterization of a cancer-associated Epstein-Barr virus EBNA1 variant reveals a novel interaction with PLOD1 and PLOD3.
Shire K et al.·Virology
2021
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
Aging

Evaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging

ACTIVE NOT RECRUITING
NCT07114536Phase NAShenzhen Hygieia Biotech Co., LtdStarted 2025-08-20
Calcium-a-ketoglutaratePlacebo(starch)

External Resources

Links to major genomics databases and tools