Book a test
On this page
⚠ Educational content only Not medical or genetic advice. Speak with a healthcare provider or genetic counsellor before acting on anything here.

PLOD1

procollagen-lysine,2-oxoglutarate 5-dioxygenase 1

The PLOD1 gene provides instructions for an enzyme called lysyl hydroxylase 1, which plays a crucial role in the proper formation and stability of collagen fibres, essential for connective tissue strength. PLOD1 encodes the enzyme lysyl hydroxylase 1, vital for modifying lysine residues within collagen.

Chromosome 1p36.22 Autosomal recessive HGNC:9081 Tier C
PLOD1 1p36.22 p arm q arm 1

PLOD1 is located on the short (p) arm of chromosome 1, at band 1p36.22. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
PLOD1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The PLOD1 gene is responsible for producing an enzyme known as lysyl hydroxylase 1. This enzyme is fundamental to the body's ability to create strong and stable connective tissues.

Connective tissues, which include skin, bones, and blood vessels, rely on collagen molecules for their structural integrity. The proper functioning of the PLOD1 gene is therefore essential for maintaining the strength and support of these vital tissues.

What the gene does

The lysyl hydroxylase 1 enzyme, encoded by the PLOD1 gene, performs a critical hydroxylation reaction. Specifically, it converts the amino acid lysine into hydroxylysine. This chemical modification is primarily observed in collagen, a key protein building block of connective tissues.

The presence of hydroxylysine within collagen molecules is crucial for their ability to form stable interconnections, known as cross-links, in the extracellular matrix. These cross-links are indispensable for generating robust collagen fibres, which provide the necessary strength and support to various body tissues. Without adequate lysyl hydroxylase 1 activity, collagen cross-linking can be impaired, leading to weakened connective tissues.

Video: Genetics 101

Chromosome location

The PLOD1 gene is situated on chromosome 1, specifically at position 1p36.22. This location refers to the short (p) arm of chromosome 1, within region 36, band 22. The gene's precise genomic position is vital for understanding its inheritance patterns and how genetic variations might affect its function.

Protein structure

The PLOD1 gene produces a protein that is 727 amino acids in length. A key functional region identified within this protein is the Fe2OG dioxygenase domain, located between amino acids 636 and 727. This domain is crucial for the enzyme's catalytic activity, enabling it to perform the hydroxylation of lysine residues.

Domain map · 727 amino acids
Fe2OG dioxygenase (636–727)Fe2OG dioxygenase636–7271~364727
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:Q02809Length:727 aaStructure:AlphaFold

Key variants

Genetic variations, or variants, within the PLOD1 gene can affect the production or function of the lysyl hydroxylase 1 enzyme. These changes can range from single base-pair alterations to larger deletions or insertions within the gene sequence. Such variants can disrupt the enzyme's ability to properly modify collagen, leading to compromised connective tissue structure and function.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for PLOD1.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1097+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.1261dup
Duplication
 p.Ala421fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.166C>T
single nucleotide variant
 p.Gln56Ter Pathogenic ★★☆☆ Familial thoracic aortic aneurysm and aortic dissection
c.1795del
Deletion
 p.Ile599fs Pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.1870del
Deletion
 p.Thr624fs Pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.1906C>T
single nucleotide variant
 p.Gln636Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.367C>T
single nucleotide variant
 p.Gln123Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.467-2del
Deletion
 - Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.698_699insCCTCTGGCCTA
Insertion
 p.Asp234fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1
c.979C>T
single nucleotide variant
 p.Gln327Ter Pathogenic ★★☆☆ Ehlers-Danlos syndrome, kyphoscoliotic type 1

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variants in the PLOD1 gene are primarily associated with inherited connective tissue disorders, notably the kyphoscoliotic type of Ehlers-Danlos syndrome. This specific form of Ehlers-Danlos syndrome is characterised by features such as unusually flexible joints and weakened tissues, which are consequences of impaired collagen structure due to the altered PLOD1 enzyme function. More than 30 different variants in the PLOD1 gene have been identified as causes of kyphoscoliotic Ehlers-Danlos syndrome.

Inheritance pattern

Conditions caused by pathogenic PLOD1 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous PLOD1 carrier status across ancestry groups?

UK clinical status

The PLOD1 gene is included in several expert-curated panels within the UK's NHS Genomic Medicine Service (GMS) pathways, as listed in PanelApp. It is green-rated for conditions such as Arthrogryposis (R83), Ehlers Danlos syndrome with a likely monogenic cause (R101), Foetal anomalies (R21), Thoracic aortic aneurysm or dissection, and Thoracic aortic aneurysm or dissection (GMS) (R125). This indicates that there is sufficient evidence for PLOD1 to be considered a confirmed cause of these conditions in a clinical diagnostic setting.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Arthrogryposis · R83 NHS GMS → Ehlers Danlos syndrome with a likely monogenic cause · R101 NHS GMS → Fetal anomalies · R21 NHS GMS → Thoracic aortic aneurysm or dissection (GMS) · R125 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary role of the PLOD1 gene?

The PLOD1 gene provides instructions for making lysyl hydroxylase 1, an enzyme critical for modifying lysine residues in collagen. This modification is essential for the formation of stable collagen cross-links, which give strength to connective tissues.

Which condition is most commonly associated with PLOD1 gene variants?

Variants in the PLOD1 gene are most commonly associated with kyphoscoliotic Ehlers-Danlos syndrome, an inherited disorder affecting connective tissues and characterised by joint hypermobility and tissue fragility.

How does PLOD1 affect collagen?

PLOD1 influences collagen by converting lysine into hydroxylysine. This hydroxylysine is then vital for creating strong cross-links between collagen molecules, which are necessary for the structural integrity and stability of connective tissues.

References

  1. Brady AF, Demirdas S, Fournel-Gigleux S. The Ehlers-Danlos syndromes, rare types. American journal of medical genetics. Part C, Seminars in medical genetics. 2017. PMID: 28306225
  2. Malfait F, Francomano C, Byers P. The 2017 international classification of the Ehlers-Danlos syndromes. American journal of medical genetics. Part C, Seminars in medical genetics. 2017. PMID: 28306229
  3. Rohrbach M, Vandersteen A, Yiş U. Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation. Orphanet journal of rare diseases. 2011. PMID: 21699693
  4. Giunta C, Bürer-Chambaz C, Steinmann B. Novel human pathological mutations. Gene symbol: PLOD1. Disease: Ehlers-Danlos syndrome type VIA, kyphoscoliotic type. Human genetics. 2009. PMID: 19320026
  5. Giunta C, Randolph A, Steinmann B. Mutation analysis of the PLOD1 gene: an efficient multistep approach to the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA). Molecular genetics and metabolism. 2005. PMID: 15979919
  6. Eyre D, Shao P, Weis MA. The kyphoscoliotic type of Ehlers-Danlos syndrome (type VI): differential effects on the hydroxylation of lysine in collagens I and II revealed by analysis of cross-linked telopeptides from urine. Molecular genetics and metabolism. 2002. PMID: 12126935
  7. Heikkinen J, Toppinen T, Yeowell H. Duplication of seven exons in the lysyl hydroxylase gene is associated with longer forms of a repetitive sequence within the gene and is a common cause for the type VI variant of Ehlers-Danlos syndrome. American journal of human genetics. 1997. PMID: 8981946
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .