PRXL2B

Chr 1

peroxiredoxin like 2B

Also known as: C1orf93, FAM213B, PM/PGFS

NCBI Gene: 127281 ENSG00000157870 UniProt: Q8TBF2

The protein catalyzes the reduction of prostaglandin H2 to prostaglandin F2alpha and reduces prostamide H2 to prostamide F2alpha using NADPH as a proton donor. The gene is not currently associated with any established Mendelian diseases in pediatric neurology. This gene shows low constraint to loss-of-function variation, suggesting tolerance to functional disruption.

ResearchSummary from RefSeq, UniProt

Predicted to enable prostaglandin F synthase activity and thioredoxin peroxidase activity. Predicted to be involved in prostaglandin biosynthetic process. Located in extracellular exosome and mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.52

Clinical Summary— PRXL2B

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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

49 VUS of 70 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.52LOEUF

pLI 0.000

Z-score 0.43

OE 0.85 (0.50–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.90 (0.77–1.07)

97 obs / 107.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.85 (0.50–1.52)

0≤0.351.4

Missense OE?0.90 (0.77–1.07)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 9.4Missense obs/exp: 97 / 107.3Syn Z: 0.12

This gene — mechanism propensity

0.6260th %ile

GOF

0.72top 25%

LOF

0.2287th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign9

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	39	9	49
Likely Benign	1	7	1	9
Benign	0	0	0	0
Total	2	46	10	58

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

View in ClinVar →

120 pathogenic / likely-pathogenic (of 140) ClinVar copy-number / structural variants overlap PRXL2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →