SPRYD3

Summary

SPRYD3 (SPRY domain containing 3, HGNC:25920) is a protein-coding gene on chromosome 12q13.13, encoding SPRY domain-containing protein 3 (Q8NCJ5).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_032840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25920
Approved symbol	SPRYD3
Name	SPRY domain containing 3
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14800
Ensembl gene	ENSG00000167778
Ensembl biotype	protein_coding
Entrez	84926

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000301463, ENST00000537540, ENST00000547257, ENST00000547837, ENST00000550252, ENST00000550564, ENST00000851412, ENST00000851413, ENST00000851414, ENST00000851415, ENST00000939794, ENST00000970160, ENST00000970161, ENST00000970162, ENST00000970163

RefSeq mRNA: 1 — MANE Select: NM_032840 NM_032840

CCDS: CCDS8845

Canonical transcript exons

ENST00000301463 — 11 exons

Exon	Start	End
ENSE00001116893	53066573	53066692
ENSE00001116909	53066314	53066486
ENSE00001315508	53064316	53065966
ENSE00002271666	53079311	53079390
ENSE00003513793	53074649	53074784
ENSE00003534084	53077115	53077261
ENSE00003567411	53067648	53067705
ENSE00003651004	53075095	53075219
ENSE00003659807	53068155	53068304
ENSE00003661696	53075736	53075811
ENSE00003693849	53073286	53073471

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 98.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.4998 / max 531.0837, expressed in 1799 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131199	21.1871	1797
131198	0.3128	128

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	98.10	gold quality
right frontal lobe	UBERON:0002810	97.66	gold quality
nucleus accumbens	UBERON:0001882	97.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.55	gold quality
anterior cingulate cortex	UBERON:0009835	97.47	gold quality
islet of Langerhans	UBERON:0000006	97.13	gold quality
frontal cortex	UBERON:0001870	97.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.06	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.69	gold quality
putamen	UBERON:0001874	96.65	gold quality
caudate nucleus	UBERON:0001873	96.59	gold quality
neocortex	UBERON:0001950	96.49	gold quality
left ventricle myocardium	UBERON:0006566	96.28	gold quality
amygdala	UBERON:0001876	96.22	gold quality
hypothalamus	UBERON:0001898	96.20	gold quality
cerebellar vermis	UBERON:0004720	96.17	gold quality
popliteal artery	UBERON:0002250	96.15	gold quality
tibial artery	UBERON:0007610	96.14	gold quality
aorta	UBERON:0000947	95.93	gold quality
mucosa of stomach	UBERON:0001199	95.84	gold quality
ascending aorta	UBERON:0001496	95.79	gold quality
thoracic aorta	UBERON:0001515	95.73	gold quality
telencephalon	UBERON:0001893	95.72	gold quality
cerebral cortex	UBERON:0000956	95.63	gold quality
forebrain	UBERON:0001890	95.62	gold quality
cerebellar cortex	UBERON:0002129	95.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.59	gold quality
cerebellar hemisphere	UBERON:0002245	95.55	gold quality
adenohypophysis	UBERON:0002196	95.47	gold quality
brain	UBERON:0000955	95.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	49.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting SPRYD3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	spryd3	ENSDARG00000101982
mus_musculus	Spryd3	ENSMUSG00000036966
rattus_norvegicus	Spryd3	ENSRNOG00000010793
caenorhabditis_elegans	gid-1	WBGENE00013202

Paralogs (3): RANBP9 (ENSG00000010017), GID8 (ENSG00000101193), RANBP10 (ENSG00000141084)

Protein

Protein identifiers

SPRY domain-containing protein 3 — Q8NCJ5 (reviewed: Q8NCJ5)

All UniProt accessions (4): B7Z1Y3, Q8NCJ5, F8VWW7, H0YI85

RefSeq proteins (1): NP_116229* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR035783	SPRYD3_SPRY	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050618	Ubq-SigPath_Reg	Family

Pfam: PF00622

UniProt features (23 total): strand 15, turn 2, chain 1, domain 1, helix 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YYO	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCJ5-F1	80.48	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, CAGCAGG_MIR370, DOUGLAS_BMI1_TARGETS_DN, CCCAGAG_MIR326, AML1_01, YYCATTCAWW_UNKNOWN, TTTGCAC_MIR19A_MIR19B, ATGTACA_MIR493, CAGTGTT_MIR141_MIR200A, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN, LINSLEY_MIR16_TARGETS, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, ASH1L_TARGET_GENES, CEBPZ_TARGET_GENES, CIITA_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRYD3	SLC61A1	Q6N075	710
SPRYD3	KCTD6	Q8NC69	526
SPRYD3	CIT	O14578	501
SPRYD3	GTPBP10	A4D1E9	500
SPRYD3	FBXO45	P0C2W1	496
SPRYD3	GOLT1B	Q9Y3E0	494
SPRYD3	GOLM2	Q6P4E1	484
SPRYD3	RESF1	Q9HCM1	448
SPRYD3	GFOD2	Q3B7J2	424
SPRYD3	RABL3	Q5HYI8	415
SPRYD3	LRRC47	Q8N1G4	412
SPRYD3	TMED2	Q15363	403
SPRYD3	PFDN5	Q99471	397
SPRYD3	USP7	Q93009	388
SPRYD3	NT5DC2	Q9H857	382

IntAct

45 interactions, top by confidence:

A	B	Type	Score
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
VCP	UBXN8	psi-mi:“MI:0914”(association)	0.690
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
IGFBP4	MYCBP2	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
IGFBP4	CETN3	psi-mi:“MI:0914”(association)	0.530
SPRYD3	MYCBP2	psi-mi:“MI:0915”(physical association)	0.370
Skp1	XPO1	psi-mi:“MI:0914”(association)	0.350
YWHAZ	WDR62	psi-mi:“MI:0914”(association)	0.350
Flnb	RPL22	psi-mi:“MI:0914”(association)	0.350
LGALS3BP	CEP290	psi-mi:“MI:0914”(association)	0.350
Lgals3bp	CS	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
USP11	PRRC2B	psi-mi:“MI:0914”(association)	0.350
MAP4	TUBA1B	psi-mi:“MI:0914”(association)	0.350
VCL	UBXN8	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
FBXO45	METTL15	psi-mi:“MI:0914”(association)	0.350
HECTD1	METTL15	psi-mi:“MI:0914”(association)	0.350
ALPK2	C2CD4B	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-Western), SPRYD3 (Two-hybrid), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS)

ESM2 similar proteins: A1L252, A8JAM0, B9EHT4, F4HX15, F4HYD7, F4JLK2, G5EFZ3, H2L2B8, O04932, O22243, O60070, O94712, P0C5E7, P34305, P49031, P49594, P69566, P97310, Q09219, Q19614, Q1LUS8, Q23541, Q28FM1, Q2R2W1, Q43845, Q5R686, Q5R881, Q5RBR6, Q61T02, Q67UX0, Q67WN8, Q67XC9, Q6FPH9, Q6P158, Q6VN19, Q8BVR6, Q8NCJ5, Q8SV03, Q8SW31, Q8VXV7

Diamond homologs: A1CNW8, A1D1S7, A1L252, A3KMV8, A6S3E0, A6ZZJ6, A7EQ00, A7TE03, O74497, O94712, P18160, P32343, P69566, Q03212, Q1E2D2, Q1LUS8, Q28FM1, Q4WRW0, Q4Z8K6, Q5RBR6, Q6BSU1, Q6FJG2, Q6VN19, Q6VN20, Q8NCJ5, Q96S59, Q96UB6, Q9PTY5, A0A5F9C6I2, D3ZXK7, F4HYD7, P53076, Q19614, Q54X16, Q5XPI3, Q5XPI4, Q84WK5, Q9C8J7, Q9SIZ8, Q5XH91

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitotic G2-G2/M phases	5	18.1×	7e-04
G2/M Transition	5	18.1×	7e-04
Mitotic Prometaphase	5	9.9×	4e-03
Cell Cycle	7	7.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

52 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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1696 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53065965:ACCT:A	acceptor_loss	1.0000
12:53065966:CCTG:C	acceptor_loss	1.0000
12:53065967:C:CA	acceptor_loss	1.0000
12:53065968:T:A	acceptor_loss	1.0000
12:53066322:T:A	donor_gain	1.0000
12:53066384:T:TA	donor_gain	1.0000
12:53066439:G:T	acceptor_gain	1.0000
12:53066443:A:T	acceptor_gain	1.0000
12:53066483:TCCC:T	acceptor_gain	1.0000
12:53066484:CCCC:C	acceptor_gain	1.0000
12:53066485:CC:C	acceptor_gain	1.0000
12:53066486:CC:C	acceptor_gain	1.0000
12:53066487:C:CA	acceptor_loss	1.0000
12:53066487:C:CC	acceptor_gain	1.0000
12:53066568:CTCA:C	donor_loss	1.0000
12:53066569:TCA:T	donor_loss	1.0000
12:53066570:CAC:C	donor_loss	1.0000
12:53066571:A:AC	donor_gain	1.0000
12:53066571:AC:A	donor_gain	1.0000
12:53066572:C:CC	donor_gain	1.0000
12:53066572:C:CT	donor_loss	1.0000
12:53066572:CC:C	donor_gain	1.0000
12:53066572:CCCT:C	donor_gain	1.0000
12:53066577:A:AC	donor_gain	1.0000
12:53066578:C:CC	donor_gain	1.0000
12:53066688:ATCGT:A	acceptor_gain	1.0000
12:53066689:TCGT:T	acceptor_gain	1.0000
12:53066690:CGT:C	acceptor_gain	1.0000
12:53066690:CGTC:C	acceptor_gain	1.0000
12:53066691:GT:G	acceptor_gain	1.0000

AlphaMissense

2916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53065863:A:T	V433D	1.000
12:53065881:A:G	L427P	1.000
12:53065887:C:T	G425E	1.000
12:53065953:C:G	R403P	1.000
12:53065959:A:G	F401S	1.000
12:53065965:A:T	V399D	1.000
12:53066602:A:G	F331S	1.000
12:53066611:C:T	G328E	1.000
12:53066613:A:C	C327W	1.000
12:53066615:A:G	C327R	1.000
12:53066617:C:T	G326D	1.000
12:53066618:C:G	G326R	1.000
12:53066626:T:A	D323V	1.000
12:53066639:A:G	C319R	1.000
12:53066647:C:T	G316E	1.000
12:53066648:C:A	G316W	1.000
12:53066648:C:G	G316R	1.000
12:53066648:C:T	G316R	1.000
12:53066659:C:T	G312E	1.000
12:53066660:C:A	G312W	1.000
12:53066660:C:G	G312R	1.000
12:53066660:C:T	G312R	1.000
12:53066676:G:C	F306L	1.000
12:53066676:G:T	F306L	1.000
12:53066677:A:C	F306C	1.000
12:53066677:A:G	F306S	1.000
12:53066678:A:C	F306V	1.000
12:53066678:A:G	F306L	1.000
12:53066678:A:T	F306I	1.000
12:53066686:C:A	G303V	1.000

dbSNP variants (sampled 300 via entrez): RS1000135073 (12:53065736 C>A), RS1000326967 (12:53079521 G>A,C,T), RS1000385419 (12:53075903 C>G), RS1000774987 (12:53080812 A>C,T), RS1001211710 (12:53075297 A>G), RS1001238757 (12:53066091 A>G), RS1001720473 (12:53081250 A>G), RS1001845125 (12:53067300 C>A), RS1002262495 (12:53080797 C>G,T), RS1002319939 (12:53074057 C>T), RS1002349269 (12:53074447 G>A), RS1002509291 (12:53070426 G>A,C), RS1002606915 (12:53064110 T>C), RS1002679178 (12:53064455 C>T), RS1002888424 (12:53066990 G>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90020028_980	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Arsenic	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Hydrogen Peroxide	affects expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Smoke	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation, decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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