OR5B21

Summary

OR5B21 (olfactory receptor family 5 subfamily B member 21, HGNC:19616) is a protein-coding gene on chromosome 11q12.1, encoding Olfactory receptor 5B21 (A6NL26). Odorant receptor.

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.

Source: NCBI Gene 219968 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 41 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.41 (intermediate), LOEUF 1.72 (unconstrained)
• MANE Select transcript: NM_001005218

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19616
Approved symbol	OR5B21
Name	olfactory receptor family 5 subfamily B member 21
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198283
Ensembl biotype	protein_coding
Entrez	219968

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000360374

ENST00000360374

RefSeq mRNA: 1 — MANE Select: NM_001005218 NM_001005218

CCDS: CCDS31552

Canonical transcript exons

ENST00000360374 — 1 exons

Exon	Start	End
ENSE00001309281	58506807	58508105

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 56.93.

Highest expression (Bgee): primordial germ cell in gonad, granulocyte, colonic epithelium, leukocyte, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

OR5B21 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.3e-02	-0.26	11:58670061:C:T

Top tissues by expression

showing 100 of 119 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.93	gold quality
granulocyte	CL:0000094	43.35	silver quality
colonic epithelium	UBERON:0000397	41.93	gold quality
leukocyte	CL:0000738	39.88	gold quality
monocyte	CL:0000576	38.96	silver quality
bone marrow cell	CL:0002092	38.17	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
tonsil	UBERON:0002372	36.12	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	32.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
lymph node	UBERON:0000029	31.91	gold quality
blood	UBERON:0000178	31.87	gold quality
right uterine tube	UBERON:0001302	31.01	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
liver	UBERON:0002107	30.67	gold quality
urinary bladder	UBERON:0001255	29.90	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.41	gold quality
placenta	UBERON:0001987	28.46	gold quality
duodenum	UBERON:0002114	28.14	gold quality
primary visual cortex	UBERON:0002436	27.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.69	silver quality
calcaneal tendon	UBERON:0003701	27.18	gold quality
islet of Langerhans	UBERON:0000006	26.98	gold quality
muscle of leg	UBERON:0001383	26.71	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
corpus callosum	UBERON:0002336	26.02	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
gastrocnemius	UBERON:0001388	25.74	gold quality
right lung	UBERON:0002167	25.31	gold quality
uterine cervix	UBERON:0000002	25.20	gold quality
pancreas	UBERON:0001264	25.10	gold quality
small intestine	UBERON:0002108	24.89	gold quality
frontal cortex	UBERON:0001870	24.80	gold quality
descending thoracic aorta	UBERON:0002345	24.77	gold quality
endometrium	UBERON:0001295	24.65	gold quality
fundus of stomach	UBERON:0001160	24.22	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
heart left ventricle	UBERON:0002084	23.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	23.88	gold quality
cortex of kidney	UBERON:0001225	23.86	gold quality
endocervix	UBERON:0000458	23.37	gold quality
myometrium	UBERON:0001296	23.19	gold quality
right lobe of liver	UBERON:0001114	23.09	gold quality
heart	UBERON:0000948	23.02	gold quality
body of pancreas	UBERON:0001150	22.90	gold quality
tibial artery	UBERON:0007610	22.76	gold quality
popliteal artery	UBERON:0002250	22.74	gold quality
intestine	UBERON:0000160	22.65	gold quality
ascending aorta	UBERON:0001496	22.64	gold quality
thoracic aorta	UBERON:0001515	22.62	gold quality
saliva-secreting gland	UBERON:0001044	22.56	gold quality
lung	UBERON:0002048	22.52	gold quality
right adrenal gland cortex	UBERON:0035827	22.43	gold quality
cerebellum	UBERON:0002037	22.41	gold quality
cerebellar cortex	UBERON:0002129	22.35	gold quality
smooth muscle tissue	UBERON:0001135	22.15	gold quality
lower esophagus mucosa	UBERON:0035834	22.15	gold quality
left uterine tube	UBERON:0001303	22.10	gold quality
adrenal tissue	UBERON:0018303	22.02	gold quality
cerebellar hemisphere	UBERON:0002245	21.96	gold quality
cerebral cortex	UBERON:0000956	21.94	gold quality
fallopian tube	UBERON:0003889	21.94	gold quality
colon	UBERON:0001155	21.93	gold quality
minor salivary gland	UBERON:0001830	21.91	gold quality
right adrenal gland	UBERON:0001233	21.81	gold quality
esophagus	UBERON:0001043	21.72	gold quality
right atrium auricular region	UBERON:0006631	21.71	gold quality
omental fat pad	UBERON:0010414	21.59	gold quality
esophagus mucosa	UBERON:0002469	21.51	gold quality
adipose tissue	UBERON:0001013	21.49	gold quality
ovary	UBERON:0000992	21.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	21.44	gold quality
upper lobe of left lung	UBERON:0008952	21.41	gold quality
transverse colon	UBERON:0001157	21.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	21.27	gold quality
subcutaneous adipose tissue	UBERON:0002190	21.24	gold quality
lower esophagus	UBERON:0013473	21.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	21.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	20.82	gold quality
brain	UBERON:0000955	20.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	20.59	gold quality
vagina	UBERON:0000996	20.53	gold quality
left coronary artery	UBERON:0001626	20.52	gold quality
right ovary	UBERON:0002118	20.36	gold quality
apex of heart	UBERON:0002098	20.28	gold quality
ectocervix	UBERON:0012249	20.21	gold quality
thyroid gland	UBERON:0002046	20.15	gold quality
temporal lobe	UBERON:0001871	20.14	gold quality
putamen	UBERON:0001874	20.09	gold quality
left ovary	UBERON:0002119	20.00	gold quality
substantia nigra	UBERON:0002038	19.99	gold quality
amygdala	UBERON:0001876	19.94	gold quality
mucosa of transverse colon	UBERON:0004991	19.91	gold quality
tibial nerve	UBERON:0001323	19.71	gold quality
prostate gland	UBERON:0002367	19.61	gold quality
skin of leg	UBERON:0001511	19.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	19.43	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.12

HPA expression

RNA tissue specificity: Not detected

6 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Nucleus accumbens	tissue	0.2
Hippocampus	tissue	0.2
Testis	tissue	0.1
Choroid plexus	tissue	0.1
Locus coeruleus	tissue	0.1
Postcentral gyrus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 173; highest nTPM — Inferior parietal lobule (0.4), Area parastriata, temporal (0.3), Area striata (0.3), Frontal eye field (0.3), Intraparietal deep sulcus (0.3).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 0.408, LOEUF 1.72, missense Z 0.441 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000360374 — one region, missense o/e 0.99.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or5b21	ENSMUSG00000046272
rattus_norvegicus	Or5b21	ENSRNOG00000089519

Paralogs (96): OR5C1 (ENSG00000148215), OR5F1 (ENSG00000149133), OR8K1 (ENSG00000150261), OR5M9 (ENSG00000150269), OR14K1 (ENSG00000153230), OR8J3 (ENSG00000167822), OR5I1 (ENSG00000167825), OR5AU1 (ENSG00000169327), OR9K2 (ENSG00000170605), OR8B12 (ENSG00000170953), OR10H3 (ENSG00000171936), OR8I2 (ENSG00000172154), OR8U1 (ENSG00000172199), OR10V1 (ENSG00000172289), OR5A1 (ENSG00000172320), OR5A2 (ENSG00000172324), OR5B12 (ENSG00000172362), OR5B2 (ENSG00000172365), OR9I1 (ENSG00000172377), OR9G4 (ENSG00000172457), OR5AR1 (ENSG00000172459), OR5AP2 (ENSG00000172464), OR8J1 (ENSG00000172487), OR5B3 (ENSG00000172769), OR10W1 (ENSG00000172772), OR5M3 (ENSG00000174937), OR5J2 (ENSG00000174957), OR10H4 (ENSG00000176231), OR5AN1 (ENSG00000176495), OR14C36 (ENSG00000177174), OR6B3 (ENSG00000178586), OR10Q1 (ENSG00000180475), OR8G2P (ENSG00000181214), OR5AK2 (ENSG00000181273), OR5AK3P (ENSG00000181282), OR5M8 (ENSG00000181371), OR8D4 (ENSG00000181518), OR8H1 (ENSG00000181693), OR8K5 (ENSG00000181752), OR8H3 (ENSG00000181761), OR8H2 (ENSG00000181767), OR5AS1 (ENSG00000181785), OR6B2 (ENSG00000182083), OR5P3 (ENSG00000182334), OR5P2 (ENSG00000183303), OR5D14 (ENSG00000186113), OR5D18 (ENSG00000186119), OR6P1 (ENSG00000186440), OR9Q1 (ENSG00000186509), OR9Q2 (ENSG00000186513), OR5D3 (ENSG00000186886), OR5W2 (ENSG00000187612), OR14I1 (ENSG00000189181), OR5K4 (ENSG00000196098), OR8A1 (ENSG00000196119), OR8D1 (ENSG00000196341), OR5AC2 (ENSG00000196578), OR14A16 (ENSG00000196772), OR8B8 (ENSG00000197125), OR11L1 (ENSG00000197591)

+36 more (showing top 60).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P37067	98.1%	Diamond
Apis mellifera ligustica	Q26418	96.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ZFP91-CNTF	ncRNA	386607
OR5B2	protein-coding	390190
OR5B12	protein-coding	390191
ZFP91	protein-coding	80829
LPXN	protein-coding	9404
CNTF	protein-coding	1270
GLYAT	protein-coding	10249
OR5B3	protein-coding	441608

Protein

Protein identifiers

Olfactory receptor 5B21 — A6NL26 (reviewed: A6NL26)

All UniProt accessions (1): A6NL26

UniProt curated annotations — full annotation on UniProt →

Function. Odorant receptor.

Subcellular location. Cell membrane.

Similarity. Belongs to the G protein-coupled receptor 1 family.

RefSeq proteins (1): NP_001005218* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000725	Olfact_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF13853

UniProt features (20 total): topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, disulfide bond 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NL26-F1	88.83	0.60

Human Protein Atlas

Protein class: G-protein coupled receptors, Odorant/olfactory and gustatory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, UniProt - Inferred from homology

Protein evidence: Evidence at transcript level

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1)

Type	Positions
Disulfide bond	95–177

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	3, 260

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-9752946	Expression and translocation of olfactory receptors	electronic
R-HSA-381753	Olfactory Signaling Pathway	—
R-HSA-9709957	Sensory Perception	—

MSigDB gene sets: 17 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, KEGG_OLFACTORY_TRANSDUCTION, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOMF_OLFACTORY_RECEPTOR_ACTIVITY, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_ODORANT_BINDING, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_SENSORY_PERCEPTION_OF_SMELL, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_DETECTION_OF_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, REACTOME_OLFACTORY_SIGNALING_PATHWAY, REACTOME_SENSORY_PERCEPTION, GOBP_DETECTION_OF_CHEMICAL_STIMULUS, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), sensory perception of smell (GO:0007608), signal transduction (GO:0007165), detection of chemical stimulus involved in sensory perception of smell (GO:0050911)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), olfactory receptor activity (GO:0004984), odorant binding (GO:0005549)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Olfactory Signaling Pathway	1
Sensory Perception	1

GO top-level categories

17 GO namespaces:

Category	Terms
transmembrane signaling receptor activity	2
G protein-coupled receptor activity	1
signal transduction	1
sensory perception of chemical stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of smell	1
detection of chemical stimulus involved in sensory perception	1
G protein-coupled receptor signaling pathway	1
detection of chemical stimulus involved in sensory perception of smell	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 138 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR5B21	TMEM109	Q9BVC6	387
OR5B21	SMR3B	P02814	386
OR5B21	SLC43A3	Q8NBI5	322
OR5B21	SLC43A1	O75387	300
OR5B21	ZDHHC5	Q9C0B5	278
OR5B21	FIGNL2	A6NMB9	258
OR5B21	PSMC3	P17980	257
OR5B21	SSRP1	Q08945	250
OR5B21	TNP2	Q05952	235
OR5B21	PLAUR	Q03405	235
OR5B21	LMBR1L	Q6UX01	212
OR5B21	SPATS2	Q86XZ4	197
OR5B21	DDB2	Q92466	195
OR5B21	HYAL4	Q2M3T9	179
OR5B21	CNGA2	Q16280	179

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
OR5B21	“up-regulates activity”	STAT3

Disease & clinical

Genetic variants

Variant evidence for OR5B21: 41 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

41 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 10 predictions of 139):

Position(s)	Effect	Δscore	Sites
11:58507451	acceptor_gain	0.8100
11:58507453	acceptor_gain	0.6800
11:58507558	acceptor_gain	0.5900
11:58507447	acceptor_gain	0.5800
11:58507437	acceptor_gain	0.5700
11:58507480	acceptor_gain	0.5500
11:58508039	donor_gain	0.5500
11:58507144	donor_gain	0.5100
11:58507437	acceptor_gain	0.4900
11:58507509	acceptor_gain	0.4700

AlphaMissense

108 missense substitutions predicted likely pathogenic (of 2,035 scored), across 44 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C177	6	0.651	0.702
F10	5	0.881	0.938
F166	5	0.753	0.861
C95	5	0.640	0.683
F175	4	0.788	0.857
F162	3	0.831	0.831
F176	3	0.823	0.823
F29	3	0.791	0.791
F274	3	0.737	0.737
S288	3	0.732	0.732
F105	3	0.707	0.707
F248	3	0.698	0.698
M116	3	0.682	0.682
F60	3	0.653	0.653
F59	3	0.648	0.648
F254	3	0.641	0.641
F102	3	0.638	0.638
F100	3	0.631	0.631
F151	3	0.595	0.595
M281	3	0.576	0.576

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST007565_92	Morning person	1e-13
GCST006924_11	Loneliness (MTAG)	8e-9
GCST006919_4	Ability to confide in someone	9e-8
GCST005537_192	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2e-7
GCST006923_4	Loneliness	3e-6
GCST004133_23	Ulcerative colitis	9e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0007865	loneliness measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.