OR5K4

Chr 3

olfactory receptor family 5 subfamily K member 4

NCBI Gene: 403278 ENSG00000196098 UniProt: A6NMS3

OR5K4 encodes an olfactory receptor that recognizes and transduces odorant signals through G-protein coupled receptor signaling in the nasal epithelium. This gene is not associated with any known human diseases and shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.93), indicating it is tolerant to genetic variation.

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 1.93

Clinical Summary— OR5K4

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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

59 VUS of 66 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?

1.93LOEUF

pLI 0.000

Z-score -0.93

OE 1.46 (0.78–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.94Z-score

OE missense 1.20 (1.07–1.35)

203 obs / 168.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.46 (0.78–1.93)

0≤0.351.4

Missense OE?1.20 (1.07–1.35)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 7 / 4.8Missense obs/exp: 203 / 168.7Syn Z: -0.31

This gene — mechanism propensity

0.84top 10%

GOF

0.85top 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

66 submitted variants in ClinVar

ClinVar

Classification Summary

VUS59

Likely Benign7

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	58	59
Likely Benign	0	7	7
Benign	0	0	0
Total	1	65	66

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap OR5K4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →