BSPRY

Summary

BSPRY (B-box and SPRY domain containing, HGNC:18232) is a protein-coding gene on chromosome 9q32, encoding B box and SPRY domain-containing protein (Q5W0U4). May regulate epithelial calcium transport by inhibiting TRPV5 activity.

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in cell leading edge; membrane; and perinuclear region of cytoplasm. Predicted to be active in cytoplasm.

Source: NCBI Gene 54836 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_017688

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18232
Approved symbol	BSPRY
Name	B-box and SPRY domain containing
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20150
Ensembl gene	ENSG00000119411
Ensembl biotype	protein_coding
OMIM	619683
Entrez	54836

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374183, ENST00000462085, ENST00000886063, ENST00000886064, ENST00000886065, ENST00000886066, ENST00000921757, ENST00000921758, ENST00000921759, ENST00000921760, ENST00000952340, ENST00000952341

RefSeq mRNA: 3 — MANE Select: NM_017688 NM_001317943, NM_001317944, NM_017688

CCDS: CCDS43868

Canonical transcript exons

ENST00000374183 — 6 exons

Exon	Start	End
ENSE00000806248	113368259	113368383
ENSE00001945800	113349541	113349780
ENSE00003521840	113354240	113354338
ENSE00003569409	113369616	113371222
ENSE00003570953	113362369	113362394
ENSE00003634014	113360507	113360737

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 98.51.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7111 / max 169.5902, expressed in 541 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98082	4.7111	541

Top tissues by expression

270 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.51	gold quality
body of pancreas	UBERON:0001150	92.92	gold quality
lower esophagus mucosa	UBERON:0035834	92.73	gold quality
cervix squamous epithelium	UBERON:0006922	92.48	silver quality
type B pancreatic cell	CL:0000169	91.12	gold quality
saliva-secreting gland	UBERON:0001044	90.95	gold quality
tongue squamous epithelium	UBERON:0006919	90.47	gold quality
palpebral conjunctiva	UBERON:0001812	89.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.58	gold quality
squamous epithelium	UBERON:0006914	89.41	gold quality
pancreas	UBERON:0001264	89.37	gold quality
esophagus mucosa	UBERON:0002469	89.32	gold quality
minor salivary gland	UBERON:0001830	89.21	gold quality
left lobe of thyroid gland	UBERON:0001120	89.19	gold quality
esophagus squamous epithelium	UBERON:0006920	89.11	gold quality
epithelium of esophagus	UBERON:0001976	89.01	gold quality
thyroid gland	UBERON:0002046	88.97	gold quality
mouth mucosa	UBERON:0003729	88.96	gold quality
right lobe of thyroid gland	UBERON:0001119	88.85	gold quality
skin of leg	UBERON:0001511	88.44	gold quality
nasal cavity mucosa	UBERON:0001826	88.27	gold quality
nasal cavity epithelium	UBERON:0005384	87.74	gold quality
mucosa of transverse colon	UBERON:0004991	87.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.34	gold quality
gingival epithelium	UBERON:0001949	87.33	gold quality
skin of abdomen	UBERON:0001416	87.22	gold quality
gingiva	UBERON:0001828	86.69	gold quality
zone of skin	UBERON:0000014	86.66	gold quality
islet of Langerhans	UBERON:0000006	86.52	gold quality
nucleus accumbens	UBERON:0001882	86.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting BSPRY, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-663B	97.40	62.91	664

Literature-anchored findings (GeneRIF, showing 1)

• Expression analysis of the rat BSPRY ortholog and demonstration of its interaction with 14-3-3 proteins. (PMID:12615066)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bspry	ENSMUSG00000028392
rattus_norvegicus	Bspry	ENSRNOG00000015105

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

B box and SPRY domain-containing protein — Q5W0U4 (reviewed: Q5W0U4)

All UniProt accessions (1): Q5W0U4

UniProt curated annotations — full annotation on UniProt →

Function. May regulate epithelial calcium transport by inhibiting TRPV5 activity.

Subunit / interactions. Interacts with TRPV5 and TRPV6. Interacts with YWHAZ/14-3-3 protein zeta.

Subcellular location. Cytoplasm. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5W0U4-1	1	yes
Q5W0U4-2	2

RefSeq proteins (3): NP_001304872, NP_001304873, NP_060158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF13765

UniProt features (10 total): sequence variant 3, splice variant 2, chain 1, domain 1, zinc finger region 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W0U4-F1	92.75	0.83

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): GOBP_RESPONSE_TO_PEPTIDE, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_MONOATOMIC_CATION_TRANSPORT, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_DENDRITIC_CELL, LIU_CMYB_TARGETS_UP, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, ZHANG_GATA6_TARGETS_DN

GO Biological Process (4): calcium ion transport (GO:0006816), innate immune response (GO:0045087), cellular response to leukemia inhibitory factor (GO:1990830), monoatomic ion transport (GO:0006811)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
metal ion transport	1
immune response	1
defense response to symbiont	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
transport	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BSPRY	TRPV5	Q9NQA5	502
BSPRY	WNK3	Q9BYP7	435
BSPRY	SLC31A2	O15432	419
BSPRY	SNRPA1	P09661	404
BSPRY	EMC8	O43402	387
BSPRY	YWHAZ	P29213	384
BSPRY	NIF3L1	Q9GZT8	369
BSPRY	LDAF1	Q96B96	364
BSPRY	PLSCR5	A0PG75	357
BSPRY	HDHD3	Q9BSH5	352
BSPRY	COPS5	Q92905	349
BSPRY	RNF207	Q6ZRF8	344
BSPRY	PPIL3	Q9H2H8	338
BSPRY	ERICH5	Q6P6B1	338
BSPRY	RNF183	Q96D59	325

IntAct

16 interactions, top by confidence:

A	B	Type	Score
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
NCS1	NMT2	psi-mi:“MI:0914”(association)	0.530
BSPRY	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
NS	BSPRY	psi-mi:“MI:0915”(physical association)	0.370
NS2	BSPRY	psi-mi:“MI:0915”(physical association)	0.370
BSPRY	NS	psi-mi:“MI:0915”(physical association)	0.370
ZYX	BSPRY	psi-mi:“MI:0915”(physical association)	0.370
CEP162	IPO5	psi-mi:“MI:0914”(association)	0.350
BSPRY	DEAF1	psi-mi:“MI:0914”(association)	0.350
BSPRY	SRGAP2	psi-mi:“MI:0914”(association)	0.350
BSPRY	ANKRD17	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): BSPRY (Affinity Capture-MS), BSPRY (Affinity Capture-MS), CEP55 (Affinity Capture-MS), DEAF1 (Affinity Capture-MS), RNF135 (Affinity Capture-MS), TMF1 (Affinity Capture-MS), HAUS4 (Affinity Capture-MS), MBLAC2 (Affinity Capture-MS), HAUS1 (Affinity Capture-MS), USP4 (Affinity Capture-MS), HSBP1 (Affinity Capture-MS), FEM1B (Affinity Capture-MS), OSBPL1A (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), BSPRY (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JXN2, A2AWP8, O88842, O95267, P29590, P52734, P98174, Q1LY10, Q29RM4, Q2TBA3, Q3TAA7, Q3U0J8, Q3UTZ3, Q496Y0, Q4VX76, Q568M3, Q58D15, Q5BIM1, Q5JSP0, Q5R5M3, Q5R5T1, Q5REJ9, Q5W0U4, Q68FF6, Q69Z89, Q69ZK0, Q6PFY8, Q7TNM2, Q7Z4K8, Q7Z5H3, Q7Z6J4, Q80V85, Q8BY35, Q8BZ52, Q8C190, Q8N1F8, Q8TCU6, Q8WVR3, Q96JH8, Q99N48

Diamond homologs: Q5TM55, Q5W0U4, Q6P6S3, Q80YW5, Q9C019, Q9TSW0, A0A2P1BRP3, A0ZSK4, O00481, Q1XHU0, Q4FZT8, Q5R996, Q62556, Q8WVV5, Q8WW59, Q91WK1, Q9HCM9, Q9JLN5, Q9QUS6, Q14142, Q5NCC9, Q7KYR7, Q7YRV4, Q9UJV3, A6NGJ6, A6NI03, A6QQX5, D4ABM4, F4I443, O15344, O70583, O95361, P82456, P82457, P82458, Q05B84, Q1ACD5, Q1ACD6, Q1ACD7, Q2YEM8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1119 predictions. Top by Δscore:

Variant	Effect	Δscore
9:113354336:GTG:G	donor_gain	1.0000
9:113360734:GATT:G	donor_gain	1.0000
9:113360736:TT:T	donor_gain	1.0000
9:113360738:G:GG	donor_gain	1.0000
9:113354238:A:AG	acceptor_gain	0.9900
9:113354239:G:GG	acceptor_gain	0.9900
9:113360505:A:AG	acceptor_gain	0.9900
9:113360506:G:GG	acceptor_gain	0.9900
9:113360506:GA:G	acceptor_gain	0.9900
9:113360506:GAGC:G	acceptor_gain	0.9900
9:113360733:TGATT:T	donor_gain	0.9900
9:113360734:GATTG:G	donor_gain	0.9900
9:113360735:ATT:A	donor_gain	0.9900
9:113360735:ATTG:A	donor_loss	0.9900
9:113360737:TGTA:T	donor_loss	0.9900
9:113360738:G:A	donor_loss	0.9900
9:113360741:AGT:A	donor_loss	0.9900
9:113360748:C:T	donor_gain	0.9900
9:113362367:A:AG	acceptor_gain	0.9900
9:113362368:G:GA	acceptor_gain	0.9900
9:113369610:TGGCA:T	acceptor_loss	0.9900
9:113369611:GGCA:G	acceptor_loss	0.9900
9:113369612:GCAGG:G	acceptor_loss	0.9900
9:113369614:A:AG	acceptor_gain	0.9900
9:113369614:A:T	acceptor_loss	0.9900
9:113369615:G:GG	acceptor_gain	0.9900
9:113354233:GTTGC:G	acceptor_loss	0.9800
9:113354234:TTGCA:T	acceptor_loss	0.9800
9:113354235:TGCA:T	acceptor_loss	0.9800
9:113354236:GCAG:G	acceptor_loss	0.9800

AlphaMissense

2607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:113369738:T:C	F269L	0.995
9:113369740:C:A	F269L	0.995
9:113369740:C:G	F269L	0.995
9:113369795:T:A	W288R	0.993
9:113369795:T:C	W288R	0.993
9:113369651:A:C	S240R	0.992
9:113369653:C:A	S240R	0.992
9:113369653:C:G	S240R	0.992
9:113369693:T:C	F254L	0.988
9:113369695:C:A	F254L	0.988
9:113369695:C:G	F254L	0.988
9:113369834:G:C	G301R	0.988
9:113369835:G:A	G301D	0.988
9:113349673:T:C	F32L	0.987
9:113349675:C:A	F32L	0.987
9:113349675:C:G	F32L	0.987
9:113369757:C:A	A275D	0.987
9:113369825:T:G	Y298D	0.987
9:113369756:G:C	A275P	0.986
9:113369661:T:C	L243P	0.985
9:113369688:T:C	L252P	0.985
9:113369835:G:T	G301V	0.985
9:113369858:C:A	R309S	0.985
9:113369739:T:C	F269S	0.984
9:113369816:A:C	S295R	0.984
9:113369818:T:A	S295R	0.984
9:113369818:T:G	S295R	0.984
9:113369896:T:A	N321K	0.984
9:113369896:T:G	N321K	0.984
9:113369903:T:C	S324P	0.984

dbSNP variants (sampled 300 via entrez): RS1000080196 (9:113349882 C>T), RS1000140313 (9:113366024 C>T), RS1000283965 (9:113369494 G>A,C), RS1000337984 (9:113355918 A>T), RS1000406186 (9:113362873 G>A,T), RS1000835228 (9:113366605 G>A), RS1001253328 (9:113359620 C>A), RS1001258147 (9:113351039 G>A,T), RS1001487341 (9:113348087 T>A,C), RS1001692855 (9:113360752 G>T), RS1001737789 (9:113348131 G>A), RS1001910760 (9:113368310 C>G), RS1001973621 (9:113354853 G>A,C), RS1002059115 (9:113361507 A>G), RS1002074457 (9:113352487 A>ACACACACACACACG)

Disease associations

OMIM: gene MIM:619683 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002831_14	Lead levels in blood	3.000000e-08
GCST90002399_81	Neutrophil percentage of white cells	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
GSK-J4	decreases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
belinostat	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Air Pollutants	increases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Silicon Dioxide	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.