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…

LOFmechanismARLOEUF 0.641 OMIM phenotype

Clinical Summary— PLOD2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 unique Pathogenic / Likely Pathogenic· 236 VUS of 549 total submissions

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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

ClinVar Variant Classifications

549 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic21

VUS236

Likely Benign174

Benign62

Conflicting19

Pathogenic

Likely Pathogenic

236

VUS

174

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	15	3	0	0	18
Likely Pathogenic	17	4	0	0	21
VUS	1	187	42	6	236
Likely Benign	0	5	107	62	174
Benign	0	1	61	0	62
Conflicting	—				19
Total	33	200	210	68	530

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap PLOD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →