OR2T4

Chr 1

olfactory receptor family 2 subfamily T member 4

Also known as: OR1-60, OR2T4Q

NCBI Gene: 127074 ENSG00000196944 UniProt: Q8NH00

OR2T4 encodes an olfactory receptor that binds odorant molecules and initiates G-protein-coupled signaling cascades to trigger smell perception. No disease associations have been established for mutations in this gene based on the available data. The gene shows tolerance to loss-of-function variants (pLI 0.19, LOEUF 0.94), which is consistent with the large redundancy typical of the olfactory receptor gene family.

ResearchSummary from RefSeq, UniProt

Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.94

Clinical Summary— OR2T4

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

📋

ClinVar Variants

47 VUS of 49 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.195

Z-score 1.69

OE 0.30 (0.12–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.88Z-score

OE missense 1.19 (1.06–1.33)

211 obs / 177.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.30 (0.12–0.94)

0≤0.351.4

Missense OE?1.19 (1.06–1.33)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 2 / 6.7Missense obs/exp: 211 / 177.9Syn Z: -1.67

This gene — mechanism propensity

0.86top 5%

GOF

0.88top 5%

LOF

0.1697th %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

49 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	43	4	47
Likely Benign	0	2	2
Benign	0	0	0
Total	43	6	49

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

View in ClinVar →

69 pathogenic / likely-pathogenic (of 99) ClinVar copy-number / structural variants overlap OR2T4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →