PLOD2

Chr 3AR

procollagen-lysine,2-oxoglutarate 5-dioxygenase 2

Also known as: BRKS2, LH2, TLH

NCBI Gene: 5352 ENSG00000152952 UniProt: O00469 OMIM: 601865

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. Mutations in the coding region of this gene are associated with Bruck syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bruck syndrome 2MIM #609220

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Bruck syndrome 2; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.51

OE 0.44 (0.31–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.56Z-score

OE missense 0.92 (0.84–1.00)

369 obs / 400.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.31–0.64)

0≤0.351.4

Missense OE?0.92 (0.84–1.00)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 20 / 45.6Missense obs/exp: 369 / 400.6Syn Z: -0.43

Background carrier burden — how many people carry a rare variant somewhere in PLOD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

1,030 rare PASS variants

Rare truncating (LoF)

1 in 250

171 rare PASS variants

Rare synonymous (reference)

1 in 150

342 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLOD2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 78	1 in 940
South Asian	~43k	1 in 51	1 in 630
Remaining (unassigned)	~30k	1 in 43	1 in 1,800
European (Finnish)	~27k	1 in 170	1 in 3,800
Admixed American	~22k	1 in 53	1 in 1,600
African / African American	~21k	1 in 69	1 in 330
East Asian	~20k	1 in 64	1 in 1,300
Ashkenazi Jewish	~13k	1 in 130	1 in 1,200
Middle Eastern	~2,883	1 in 56	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 20 coding exons well covered in gnomAD exomes; exon 16 poorly covered; exons 2, 5, 6, 7, 8 and 6 more marginal. Genomes: all 20.? see exons ↓