OR5K1

Chr 3

olfactory receptor family 5 subfamily K member 1

Also known as: HSHTPCRX10, HTPCRX10, OR3-8

NCBI Gene: 26339 ENSG00000232382 UniProt: Q8NHB7

OR5K1 encodes an olfactory receptor that detects odorant molecules and initiates G-protein-coupled signaling to trigger smell perception. This gene is not well-established as a cause of human disease, and pathogenic variants have not been clearly associated with specific neurological or developmental disorders. The gene shows very low constraint against loss-of-function variants, suggesting that complete loss of this single olfactory receptor is likely tolerated.

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— OR5K1

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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

62 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 -1.10

OE 1.52 (0.84–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.26Z-score

OE missense 1.28 (1.14–1.44)

202 obs / 157.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.52 (0.84–1.93)

0≤0.351.4

Missense OE?1.28 (1.14–1.44)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 8 / 5.3Missense obs/exp: 202 / 157.4Syn Z: -1.35

This gene — mechanism propensity

0.84top 10%

GOF

0.83top 10%

LOF

0.1895th %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

66 submitted variants in ClinVar

ClinVar

Classification Summary

VUS62

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	62	62
Likely Benign	4	4
Benign	0	0
Total	66	66

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap OR5K1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →