GeneBe

PLOD1

protein-coding

procollagen-lysine,2-oxoglutarate 5-dioxygenase 1, the group of Procollagen-lysine,2-oxoglutarate 5-dioxygenase family

Gene summary

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]

Previous symbols:
  • LLH
  • PLOD

MANE transcript

NM_000302.4

Inheritance

AR

ClinVar variants

P:120U:513B:388

Top phenotype

Ehlers-Danlos syndrome, kyphoscoliotic type, 1

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr1:11,934,205-11,975,538

External References & Databases

Ensembl (ENSG00000083444)NCBI Gene (5351)OMIM (153454)HGNC:9081GenCCUniProt (Q02809)AlphaFoldClinVar (PLOD1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~41.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ehlers-Danlos syndrome, kyphoscoliotic type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0016002

Submitter: Labcorp Genetics (formerly Invitae)

Ehlers-Danlos syndrome, kyphoscoliotic type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0016002

Submitter: Genomics England PanelApp

Ehlers-Danlos syndrome, kyphoscoliotic type 1SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016002

Submitter: Orphanet

Ehlers-Danlos syndrome, kyphoscoliotic type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0016002

Submitter: PanelApp Australia

Ehlers-Danlos syndrome, kyphoscoliotic type 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016002

Submitter: G2P

Clinical Genomic Database (CGD)

Ehlers-Danlos syndrome, kyphoscoliotic type, 1AR

Manifestation: Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic; Renal

Intervention: Cardiovascular; Ophthalmologic; Renal

Rationale: EDS VI may be clinically recognizable, but care may be considered related to issues such as potential severe vascular rupture (beneficial preventive measures include blood pressure management); Adequate hydration to prevent nephroliathisis may be beneficial; Though not frequent, individuals may demonstrate ophthalmologic sequelae (eg, glaucoma), and appropriate surveillance and preventive measures may be beneficial

Refs: 4342967; 5027136; 5016372; 4373475; 1184396; 429005; 2504907; 8449506; 7977351; 8574422; 9152832; 9220536; 9557891; 9686670; 15666309; 15979919; 16329110; 17100196; 19320026; 20301635; 22001912Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLOD1 variants in ClinVar

29 Conditions Cataloged
Ehlers-Danlos syndrome, kyphoscoliotic type 1Total: 981
Familial thoracic aortic aneurysm and aortic dissectionTotal: 615
not providedTotal: 283
not specifiedTotal: 231
PLOD1-related disorderTotal: 59
Ehlers-Danlos syndromeTotal: 36
Cardiovascular phenotypeTotal: 3
HydrocephalusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000302.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
7
clinvar
339
clinvar
7
clinvar
 354
missense
1
clinvar
6
clinvar
489
clinvar
40
clinvar
2
clinvar
 538
nonsense
24
clinvar
8
clinvar
2
clinvar
 34
start loss
2
clinvar
 2
frameshift
21
clinvar
20
clinvar
3
clinvar
 44
splice donor/acceptor (+/-2bp)
4
clinvar
33
clinvar
12
clinvar
 49
Total526851337991021

Highest pathogenic variant AF is 0.000118987125

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000302.4RefSeqNP_000293.219MANE Select
ENST00000196061.5EnsemblENSP00000196061.419MANE Select
NM_001316320.2RefSeqNP_001303249.120Standard
ENST00000429000.6EnsemblENSP00000405372.18Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
plod1aDanio rerio

Structure: actinotrichium

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Lysine degradation - Homo sapiens (human)
  • Collagen biosynthesis and modifying enzymes
  • Collagen formation
  • Extracellular matrix organization

Biological Process

  • response to hypoxia
  • cellular protein modification process
  • protein O-linked glycosylation
  • epidermis development
  • peptidyl-lysine hydroxylation

Molecular Function

  • iron ion binding
  • procollagen-lysine 5-dioxygenase activity
  • L-ascorbic acid binding
  • procollagen glucosyltransferase activity
  • protein homodimerization activity

Cellular Component

  • endoplasmic reticulum membrane
  • rough endoplasmic reticulum membrane
  • extracellular exosome
  • catalytic complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000196061
Coding exons
19
Length
41334
Individuals with no LoFs
125690
Homozygous LoFs
0
Heterozygous LoFs
58
Defined
125748
p
0.000231
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.3944234460.9480.00003064752
Missense (PolyPhen)111118.160.939391226
Synonymous-0.4781981901.040.00001361421
Loss of Function1.883043.40.6920.00000245452

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian0.000330.00033rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000320.00032rare
South Asian0.000200.00020rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (By similarity). Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:8621606, PubMed:10686424, PubMed:15854030). These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links (Probable). {ECO:0000250|UniProtKB:Q9R0E2, ECO:0000269|PubMed:10686424, ECO:0000269|PubMed:15854030, ECO:0000269|PubMed:8621606, ECO:0000305}.;
Disease
DISEASE: Ehlers-Danlos syndrome, kyphoscoliotic type, 1 (EDSKSCL1) [MIM:225400]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSKSCL1 is an autosomal recessive form characterized by severe muscle hypotonia at birth, generalized joint laxity, scoliosis at birth, and scleral fragility and rupture of the ocular globe. {ECO:0000269|PubMed:10686424, ECO:0000269|PubMed:15666309, ECO:0000269|PubMed:15854030, ECO:0000269|PubMed:15979919, ECO:0000269|PubMed:8163671, ECO:0000269|PubMed:9617436}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool
0.378
RVIS EVS
-0.66
RVIS percentile EVS
16.09

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.666

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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