OBP2A

Chr 9

odorant binding protein 2A

Also known as: LCN13, OBP, OBP2C, OBPIIa, hOBPIIa

NCBI Gene: 29991 ENSG00000122136 UniProt: Q9NY56

This gene encodes a small extracellular protein belonging to the lipocalin superfamily. The protein is thought to transport small, hydrophobic, volatile molecules or odorants through the nasal mucus to olfactory receptors, and may also function as a scavenger of highly concentrated or toxic odors. The protein is expressed as a monomer in the nasal mucus, and can bind diverse types of odorants with a higher affinity for aldehydes and fatty acids. This gene and a highly similar family member are located in a cluster of lipocalin genes on chromosome 9. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Active trials

Pathogenic / LP

120

ClinVar variants

Pubs (1 yr)

-0.0

Missense Z

1.66

LOEUF

Clinical Summary— OBP2A

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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

56 Pathogenic / Likely Pathogenic· 56 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.66LOEUF

pLI 0.000

Z-score 0.07

OE 0.98 (0.59–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.03Z-score

OE missense 1.01 (0.86–1.19)

102 obs / 101.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.98 (0.59–1.66)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.86–1.19)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18

0≤1.21.6

LoF obs/exp: 9 / 9.2Missense obs/exp: 102 / 101.1Syn Z: -0.91

0.7131th %ile

GOF

0.6346th %ile

LOF

0.1598th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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.