SPDYE5

Summary

SPDYE5 (speedy/RINGO cell cycle regulator family member E5, HGNC:35464) is a protein-coding gene on chromosome 7q11.23, encoding Speedy protein E5 (A6NIY4). It is a selective cancer dependency (DepMap: 60.0% of cell lines).

Predicted to enable protein kinase binding activity. Predicted to be involved in positive regulation of cyclin-dependent protein serine/threonine kinase activity.

Source: NCBI Gene 442590 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 92 total
• Cancer dependency (DepMap): dependent in 60.0% of screened cell lines
• MANE Select transcript: NM_001306141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35464
Approved symbol	SPDYE5
Name	speedy/RINGO cell cycle regulator family member E5
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170092
Ensembl biotype	protein_coding
Entrez	442590

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000625065

RefSeq mRNA: 1 — MANE Select: NM_001306141 NM_001306141

CCDS: CCDS78241

Canonical transcript exons

ENST00000625065 — 9 exons

Exon	Start	End
ENSE00001599218	75501362	75501755
ENSE00002439498	75495156	75495374
ENSE00003533963	75499231	75499316
ENSE00003679008	75497938	75497996
ENSE00003758563	75493627	75494207
ENSE00003758807	75502833	75504316
ENSE00003759401	75496674	75496904
ENSE00003759910	75501878	75501982
ENSE00003937692	75492320	75492441

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 81.05.

Top tissues by expression

133 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	81.05	gold quality
sural nerve	UBERON:0015488	76.32	gold quality
bone marrow cell	CL:0002092	73.93	silver quality
stromal cell of endometrium	CL:0002255	70.55	gold quality
tonsil	UBERON:0002372	69.20	gold quality
bone marrow	UBERON:0002371	67.29	gold quality
lower esophagus mucosa	UBERON:0035834	67.16	gold quality
colonic epithelium	UBERON:0000397	67.01	silver quality
blood	UBERON:0000178	65.26	gold quality
skeletal muscle tissue	UBERON:0001134	65.07	gold quality
testis	UBERON:0000473	64.23	gold quality
liver	UBERON:0002107	63.93	gold quality
cortical plate	UBERON:0005343	63.77	gold quality
left testis	UBERON:0004533	63.64	gold quality
mucosa of transverse colon	UBERON:0004991	63.16	gold quality
right testis	UBERON:0004534	63.14	gold quality
right lobe of thyroid gland	UBERON:0001119	63.08	gold quality
ventricular zone	UBERON:0003053	62.96	gold quality
uterine cervix	UBERON:0000002	62.84	gold quality
urinary bladder	UBERON:0001255	62.69	gold quality
thyroid gland	UBERON:0002046	62.30	gold quality
adrenal tissue	UBERON:0018303	62.18	gold quality
left lobe of thyroid gland	UBERON:0001120	62.15	gold quality
spleen	UBERON:0002106	62.11	gold quality
cortex of kidney	UBERON:0001225	61.71	gold quality
primary visual cortex	UBERON:0002436	61.70	gold quality
right lobe of liver	UBERON:0001114	61.61	gold quality
calcaneal tendon	UBERON:0003701	61.58	gold quality
myometrium	UBERON:0001296	61.47	gold quality
zone of skin	UBERON:0000014	61.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.33

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.0% of screened cell lines.

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), SPDYE2B (ENSG00000173678), SPDYE4 (ENSG00000183318), SPDYE12 (ENSG00000184616), SPDYE16 (ENSG00000185040), SPDYE17 (ENSG00000186645), SPDYE2 (ENSG00000205238), SPDYE18 (ENSG00000205482), SPDYE3 (ENSG00000214300), SPDYE21 (ENSG00000230358), SPDYE6 (ENSG00000260097), SPDYE9 (ENSG00000262461), SPDYE8 (ENSG00000273520), SPDYE10 (ENSG00000274570), SPDYE11 (ENSG00000275976), SPDYE15 (ENSG00000286014), SPDYE13 (ENSG00000286038), SPDYE14 (ENSG00000286137)

Protein

Protein identifiers

Speedy protein E5 — A6NIY4 (reviewed: A6NIY4)

All UniProt accessions (1): A6NIY4

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the Speedy/Ringo family.

RefSeq proteins (1): NP_001293070* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020984	Speedy	Family
IPR057742	Speedy_E	Family

Pfam: PF11357

UniProt features (4 total): compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NIY4-F1	60.45	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): chr7q11, GOMF_KINASE_BINDING, MIR153_5P, MIR3662, MIR607, MIR1277_5P, MIR95_5P, MIR3121_3P, MIR1297, MIR26A_5P, MIR26B_5P, MIR545_3P, MIR3924, MIR4465, 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

42 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPDYE5	LRRC37A	A6NMS7	610
SPDYE5	LRRC37A3	O60309	608
SPDYE5	GOLGA6L10	A6NI86	507
SPDYE5	NBPF9	P0DPF3	479
SPDYE5	NBPF11	Q86T75	446
SPDYE5	NBPF14	Q5TI25	446
SPDYE5	NBPF15	Q8N660	418
SPDYE5	NOTCH2NLB	P0DPK3	308
SPDYE5	LINS1	Q8NG48	290
SPDYE5	NBPF10	Q6P3W6	271
SPDYE5	RHCE	P18577	249
SPDYE5	PRDM9	Q9NQV7	213
SPDYE5	SPDYE1	Q8NFV5	0
SPDYE5	CDK2	P24941	0
SPDYE5	CDC25C	P30307	0
SPDYE5	SPDYA	Q5MJ70	0
SPDYE5	SPDYC	Q5MJ68	0
SPDYE5	CDK1	P06493	0

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0J9YY54, A0A494C086, A0A494C0Z2, A0A494C191, A6NHP3, A6NIY4, A6NJR5, A6NNV3, B4DH59, F6SZT2, P0C6Y7, P0CI01, P0DKJ7, P0DKJ8, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P79386, Q08AG5, Q13342, Q16666, Q3BBV2, Q495Y8, Q587J8, Q5JRC9, Q5QGU6, Q5RD14, Q5RKG3, Q63HK3, Q6ITT4, Q7TQI8, Q86T75, Q8IWY8, Q8N660, Q8NFV5

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

900 predictions. Top by Δscore:

Variant	Effect	Δscore
7:75494189:G:GT	donor_gain	1.0000
7:75501360:A:AG	acceptor_gain	1.0000
7:75501361:G:GG	acceptor_gain	1.0000
7:75501752:GGAG:G	donor_gain	1.0000
7:75501753:GAGG:G	donor_gain	1.0000
7:75501754:AGG:A	donor_loss	1.0000
7:75501757:T:G	donor_loss	1.0000
7:75494174:G:GT	donor_gain	0.9900
7:75494178:T:TA	donor_gain	0.9900
7:75494179:G:GA	donor_gain	0.9900
7:75494205:CAG:C	donor_loss	0.9900
7:75494207:GGTGA:G	donor_loss	0.9900
7:75494208:G:GA	donor_loss	0.9900
7:75494209:T:A	donor_loss	0.9900
7:75497936:A:AG	acceptor_gain	0.9900
7:75497937:G:GG	acceptor_gain	0.9900
7:75499317:G:GG	donor_gain	0.9900
7:75501356:CCTCA:C	acceptor_loss	0.9900
7:75501357:CTCAG:C	acceptor_loss	0.9900
7:75501358:TCA:T	acceptor_loss	0.9900
7:75501360:AG:A	acceptor_loss	0.9900
7:75501361:G:GA	acceptor_loss	0.9900
7:75501361:GCT:G	acceptor_gain	0.9900
7:75501361:GCTA:G	acceptor_gain	0.9900
7:75501361:GCTAC:G	acceptor_gain	0.9900
7:75501431:G:GT	donor_gain	0.9900
7:75496897:GCTGC:G	donor_gain	0.9800
7:75496956:G:GT	donor_gain	0.9800
7:75496957:A:T	donor_gain	0.9800
7:75497935:CAG:C	acceptor_gain	0.9800

AlphaMissense

2655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:75497958:T:C	F211L	0.990
7:75497960:C:A	F211L	0.990
7:75497960:C:G	F211L	0.990
7:75496889:T:C	F199L	0.986
7:75496891:C:A	F199L	0.986
7:75496891:C:G	F199L	0.986
7:75501404:A:C	K266N	0.983
7:75501404:A:T	K266N	0.983
7:75499258:T:C	F233L	0.979
7:75499260:C:A	F233L	0.979
7:75499260:C:G	F233L	0.979
7:75497959:T:C	F211S	0.977
7:75499306:T:C	F249L	0.975
7:75499308:C:A	F249L	0.975
7:75499308:C:G	F249L	0.975
7:75497971:A:C	D215A	0.969
7:75497971:A:T	D215V	0.967
7:75497992:A:T	D222V	0.959
7:75496890:T:C	F199S	0.958
7:75501420:T:C	F272L	0.958
7:75501422:C:A	F272L	0.958
7:75501422:C:G	F272L	0.958
7:75501403:A:T	K266I	0.955
7:75497970:G:C	D215H	0.953
7:75499235:T:C	L225P	0.951
7:75499259:T:C	F233S	0.950
7:75499255:T:G	Y232D	0.946
7:75499303:T:C	F248L	0.946
7:75499305:C:A	F248L	0.946
7:75499305:C:G	F248L	0.946

dbSNP variants (sampled 300 via entrez): RS10230587 (7:75494283 C>A,T), RS10274653 (7:75491667 C>G,T), RS10441325 (7:75494456 C>A,G,T), RS1062117 (7:75493577 G>A,C), RS111295044 (7:75494029 C>A), RS112356339 (7:75495039 A>G), RS112531644 (7:75491716 T>G), RS112606868 (7:75490582 G>A,C), RS112624224 (7:75490107 C>T), RS112778680 (7:75502906 G>A), RS113247842 (7:75498758 G>A,T), RS113429735 (7:75495770 T>A,C), RS113743614 (7:75494937 A>G), RS113790339 (7:75490861 G>A), RS113959810 (7:75504494 T>A)

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
GCST008361_9	Response to cognitive-behavioural therapy in major depressive disorder	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pentanal	decreases expression	1
2-palmitoylglycerol	increases expression	1
Cadmium	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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