OR5H6

Chr 3

olfactory receptor family 5 subfamily H member 6

Also known as: OR3-11

NCBI Gene: 79295 ENSG00000230301 UniProt: Q8NGV6

OR5H6 encodes an olfactory receptor that detects odorant molecules in the nose 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 it shows no constraint against loss-of-function variants in the population. No Mendelian diseases have been definitively associated with OR5H6 mutations.

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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.86

Clinical Summary— OR5H6

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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

53 VUS of 61 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?

1.86LOEUF

pLI 0.000

Z-score -0.23

OE 1.12 (0.56–1.86)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.07Z-score

OE missense 1.45 (1.31–1.62)

239 obs / 164.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.12 (0.56–1.86)

0≤0.351.4

Missense OE?1.45 (1.31–1.62)

0≤0.61.4

Synonymous OE?1.44

0≤1.21.6

LoF obs/exp: 5 / 4.5Missense obs/exp: 239 / 164.3Syn Z: -2.70

This gene — mechanism propensity

0.82top 10%

GOF

0.86top 5%

LOF

0.1796th %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

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS53

Likely Benign8

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	53	0	53
Likely Benign	7	1	8
Benign	0	0	0
Total	60	1	61

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap OR5H6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →