OR8B4

Chr 11

olfactory receptor family 8 subfamily B member 4

Also known as: OR11-315, OR8B4P

OR8B4 encodes an olfactory receptor that binds odorant molecules and initiates G-protein-coupled signaling to trigger smell perception. This gene is a segregating pseudogene where some individuals carry functional alleles while others have non-functional variants, and no Mendelian diseases have been associated with OR8B4 mutations. The gene shows low constraint to loss-of-function variation (pLI = 0.03, LOEUF = 1.32), consistent with its variable functionality across the population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
60
P/LP submissions
0%
P/LP missense
1.32
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryOR8B4
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 42 VUS of 105 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.32LOEUF
pLI 0.028
Z-score 1.08
OE 0.52 (0.231.32)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.43Z-score
OE missense 0.91 (0.791.04)
148 obs / 163.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.231.32)
00.351.4
Missense OE0.91 (0.791.04)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 3 / 5.8Missense obs/exp: 148 / 163.3Syn Z: -0.34
DN
0.86top 5%
GOF
0.87top 5%
LOF
0.1299th %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

105 submitted variants in ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic2
VUS42
Likely Benign3
58
Pathogenic
2
Likely Pathogenic
42
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
58
0
58
Likely Pathogenic
0
0
2
0
2
VUS
0
39
3
0
42
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total041631105

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

View in ClinVar →

Protein Context — Lollipop Plot

OR8B4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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