OR4D2

Chr 17

olfactory receptor family 4 subfamily D member 2

Also known as: BC2009, OR17-24

The OR4D2 protein is an olfactory receptor that recognizes and transduces odorant signals through G-protein coupling in nasal sensory neurons. No definitive disease associations have been established for OR4D2 mutations in the provided clinical data. The gene shows tolerance to loss-of-function variation with a low pLI score, though a predicted gain-of-function mechanism suggests potential pathogenicity through altered odorant receptor function.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
0
Pubs (1 yr)
15
P/LP submissions
0%
P/LP missense
1.60
LOEUF
GOF
Mechanism· predicted
Clinical SummaryOR4D2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 48 VUS of 68 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.60LOEUF
pLI 0.001
Z-score 0.48
OE 0.79 (0.411.60)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.20Z-score
OE missense 1.04 (0.921.19)
169 obs / 161.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.79 (0.411.60)
00.351.4
Missense OE1.04 (0.921.19)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 5 / 6.3Missense obs/exp: 169 / 161.8Syn Z: -0.43
DN
0.90top 5%
GOF
0.88top 5%
LOF
0.1399th %ile

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

DNprediction above median
GOFprediction 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

68 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS48
Likely Benign5
14
Pathogenic
1
Likely Pathogenic
48
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
0
47
1
0
48
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total05216068

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

View in ClinVar →

Protein Context — Lollipop Plot

OR4D2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found