SPDYE3

Summary

SPDYE3 (speedy/RINGO cell cycle regulator family member E3, HGNC:35462) is a protein-coding gene on chromosome 7q22.1, encoding Speedy protein E3 (A6NKU9).

Predicted to enable protein kinase binding activity.

Source: NCBI Gene 441272 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_001004351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35462
Approved symbol	SPDYE3
Name	speedy/RINGO cell cycle regulator family member E3
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000214300
Ensembl biotype	protein_coding
OMIM	617625
Entrez	441272

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000332397, ENST00000380765

RefSeq mRNA: 1 — MANE Select: NM_001004351 NM_001004351

CCDS: CCDS47658

Canonical transcript exons

ENST00000332397 — 11 exons

Exon	Start	End
ENSE00001531352	100320891	100322196
ENSE00003275404	100319931	100320035
ENSE00003497873	100308974	100309192
ENSE00003510551	100310360	100310578
ENSE00003530413	100313140	100313358
ENSE00003534078	100311750	100311968
ENSE00003554812	100314532	100314750
ENSE00003568425	100319565	100319808
ENSE00003570013	100307702	100307991
ENSE00003676086	100315785	100315843
ENSE00003679548	100317070	100317155

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 76.18.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.18	gold quality
bone marrow cell	CL:0002092	69.98	silver quality
colonic epithelium	UBERON:0000397	67.20	silver quality
sural nerve	UBERON:0015488	67.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	62.39	gold quality
testis	UBERON:0000473	61.26	gold quality
left testis	UBERON:0004533	60.66	gold quality
bone marrow	UBERON:0002371	60.48	silver quality
right testis	UBERON:0004534	60.35	gold quality
adrenal tissue	UBERON:0018303	59.00	gold quality
stromal cell of endometrium	CL:0002255	58.61	gold quality
tonsil	UBERON:0002372	56.52	silver quality
skeletal muscle tissue	UBERON:0001134	56.08	silver quality
calcaneal tendon	UBERON:0003701	53.19	silver quality
muscle tissue	UBERON:0002385	52.42	gold quality
ganglionic eminence	UBERON:0004023	51.94	gold quality
cerebellum	UBERON:0002037	51.82	gold quality
cerebellar cortex	UBERON:0002129	51.70	gold quality
cerebellar hemisphere	UBERON:0002245	51.36	gold quality
ventricular zone	UBERON:0003053	50.44	gold quality
blood	UBERON:0000178	50.26	gold quality
endometrium	UBERON:0001295	49.91	silver quality
liver	UBERON:0002107	49.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	49.37	gold quality
kidney	UBERON:0002113	49.24	gold quality
cortex of kidney	UBERON:0001225	48.97	gold quality
urinary bladder	UBERON:0001255	48.78	gold quality
superior frontal gyrus	UBERON:0002661	48.74	gold quality
vermiform appendix	UBERON:0001154	48.46	gold quality
lymph node	UBERON:0000029	47.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting SPDYE3, 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-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-369-3P	99.85	70.52	2264

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spdye4b	ENSMUSG00000029586
mus_musculus	Spdye4a	ENSMUSG00000039296
rattus_norvegicus	Spdye4	ENSRNOG00000058563

Paralogs (18): SPDYE1 (ENSG00000136206), SPDYE5 (ENSG00000170092), SPDYE2B (ENSG00000173678), SPDYE4 (ENSG00000183318), SPDYE12 (ENSG00000184616), SPDYE16 (ENSG00000185040), SPDYE17 (ENSG00000186645), SPDYE2 (ENSG00000205238), SPDYE18 (ENSG00000205482), SPDYE21 (ENSG00000230358), SPDYE6 (ENSG00000260097), SPDYE9 (ENSG00000262461), SPDYE8 (ENSG00000273520), SPDYE10 (ENSG00000274570), SPDYE11 (ENSG00000275976), SPDYE15 (ENSG00000286014), SPDYE13 (ENSG00000286038), SPDYE14 (ENSG00000286137)

Protein

Protein identifiers

Speedy protein E3 — A6NKU9 (reviewed: A6NKU9)

All UniProt accessions (1): A6NKU9

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Predominantly expressed in testis and spleen.

Similarity. Belongs to the Speedy/Ringo family.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NKU9-1	1	yes
A6NKU9-2	2

RefSeq proteins (1): NP_001004351* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020984	Speedy	Family
IPR057742	Speedy_E	Family

Pfam: PF11357

UniProt features (14 total): compositionally biased region 6, region of interest 5, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKU9-F1	50.78	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): ACEVEDO_LIVER_CANCER_UP, GOMF_KINASE_BINDING, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, NFE2L2.V2, MIR3662, MIR1277_5P, MIR3671, MIR95_5P, MIR3121_3P, MIR3924, MIR4291, MIR3120_3P, MIR410_3P

GO Biological Process (1): positive regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0045737)

GO Molecular Function (1): protein kinase binding (GO:0019901)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein serine/threonine kinase activity	1
positive regulation of cell cycle	1
positive regulation of protein serine/threonine kinase activity	1
positive regulation of cyclin-dependent protein kinase activity	1
kinase binding	1

Protein interactions and networks

STRING

142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPDYE3	EBLN2	Q6P2I7	570
SPDYE3	TTC34	A8MYJ7	445
SPDYE3	PRAMEF14	Q5SWL7	432
SPDYE3	POU5F2	Q8N7G0	418
SPDYE3	MROH1	Q8NDA8	417
SPDYE3	FAM124B	Q9H5Z6	414
SPDYE3	DNHD1	Q96M86	398
SPDYE3	ZBTB12	Q9Y330	393
SPDYE3	GIGYF1	O75420	371
SPDYE3	PRDM7	Q9NQW5	371
SPDYE3	LY6G6F	Q5SQ64	367
SPDYE3	ICA1L	Q8NDH6	355
SPDYE3	MPV17L	Q2QL34	354
SPDYE3	KLHL11	Q9NVR0	349
SPDYE3	PITPNB	P48739	349

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SPDYE7P	SPDYE3	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): SPDYE3 (Affinity Capture-MS), SPDYE3 (Negative Genetic), SPDYE3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0U1RQI7, A0A1D9BZF0, A6NJU9, A6NKU9, A6NNC1, A6QL64, A8MRT5, B2SU53, B4DH59, B5DUH6, C9JG80, E5RHQ5, F8W0I5, P01068, P02895, P06916, P07907, P0DKL2, P0DPF3, P0DRJ4, P13208, P14417, P32072, P83060, Q26755, Q3BBV0, Q3BBV2, Q4ZJY7, Q4ZJZ0, Q4ZJZ1, Q4ZJZ3, Q5TAG4, Q5TI25, Q6P3W6, Q6RY98, Q7T3L1, Q86SG3, Q86T75

Diamond homologs: A0A494C086, A0A494C0Z2, A0A494C191, A6NHP3, A6NIY4, A6NJR5, A6NKU9, A6NLX3, A6NNV3, P0CI01, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, Q495Y7, Q495Y8, Q5IBH6, Q5IBH7, Q5MJ68, Q5MJ70, Q8NFV5, Q8R496, Q9PU13, Q9YGL1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1614 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100307958:G:GT	donor_gain	1.0000
7:100319634:G:GT	donor_gain	1.0000
7:100319634:G:T	donor_gain	1.0000
7:100319709:G:GT	donor_gain	1.0000
7:100319778:GGCT:G	donor_gain	1.0000
7:100307913:G:GT	donor_gain	0.9900
7:100307963:G:GA	donor_gain	0.9900
7:100307973:G:GT	donor_gain	0.9900
7:100315783:A:AG	acceptor_gain	0.9900
7:100315784:G:GG	acceptor_gain	0.9900
7:100317211:G:GT	donor_gain	0.9900
7:100317211:G:T	donor_gain	0.9900
7:100319563:A:AG	acceptor_gain	0.9900
7:100319564:G:GG	acceptor_gain	0.9900
7:100319929:A:AG	acceptor_gain	0.9900
7:100319930:G:GG	acceptor_gain	0.9900
7:100320889:A:AG	acceptor_gain	0.9900
7:100320890:G:GA	acceptor_gain	0.9900
7:100320890:GA:G	acceptor_gain	0.9900
7:100307962:T:TA	donor_gain	0.9800
7:100307988:TCAG:T	donor_loss	0.9800
7:100307989:CAG:C	donor_loss	0.9800
7:100307990:AG:A	donor_loss	0.9800
7:100307991:GG:G	donor_loss	0.9800
7:100307992:G:GA	donor_loss	0.9800
7:100315783:AGAG:A	acceptor_gain	0.9800
7:100315784:GAGG:G	acceptor_gain	0.9800
7:100319564:GCT:G	acceptor_gain	0.9800
7:100319628:G:GG	donor_gain	0.9800
7:100319660:GCCC:G	donor_gain	0.9800

AlphaMissense

3579 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100314735:T:C	F396L	0.986
7:100314737:C:A	F396L	0.986
7:100314737:C:G	F396L	0.986
7:100317097:T:C	F430L	0.986
7:100317099:C:A	F430L	0.986
7:100317099:C:G	F430L	0.986
7:100315805:T:C	F408L	0.983
7:100315807:C:A	F408L	0.983
7:100315807:C:G	F408L	0.983
7:100311953:T:C	F250L	0.978
7:100311955:C:A	F250L	0.978
7:100311955:C:G	F250L	0.978
7:100317142:T:C	F445L	0.973
7:100317144:C:A	F445L	0.973
7:100317144:C:G	F445L	0.973
7:100317145:T:C	F446L	0.973
7:100317147:C:A	F446L	0.973
7:100317147:C:G	F446L	0.973
7:100319623:T:C	F469L	0.970
7:100319625:C:A	F469L	0.970
7:100319625:C:G	F469L	0.970
7:100315818:A:T	D412V	0.969
7:100315806:T:C	F408S	0.967
7:100317098:T:C	F430S	0.964
7:100310563:T:C	F177L	0.962
7:100310565:C:A	F177L	0.962
7:100310565:C:G	F177L	0.962
7:100315839:A:T	D419V	0.962
7:100319755:T:C	F513L	0.962
7:100319757:C:A	F513L	0.962

dbSNP variants (sampled 300 via entrez): RS1000234077 (7:100315187 G>A,T), RS1000388372 (7:100306028 C>A,T), RS1000972591 (7:100312891 A>C,G), RS1000978959 (7:100319238 G>A,C), RS1001312738 (7:100317784 T>C,G), RS1001364587 (7:100318094 G>A), RS1002239263 (7:100310055 C>T), RS1002592021 (7:100309676 G>A,C), RS1002680662 (7:100317884 G>T), RS1002982779 (7:100316450 A>G), RS1002983437 (7:100308003 G>A), RS1003036587 (7:100316662 G>A,C), RS1003316911 (7:100315262 G>C), RS1003370717 (7:100315468 G>A), RS1003667751 (7:100321304 A>T)

Disease associations

OMIM: gene MIM:617625 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010002_259	Refractive error	3.000000e-16
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
bisphenol A	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Silicon Dioxide	decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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