SPDYE4

Summary

SPDYE4 (speedy/RINGO cell cycle regulator family member E4, HGNC:35463) is a protein-coding gene on chromosome 17p13.1, encoding Speedy protein E4 (A6NLX3).

Predicted to enable protein kinase binding activity.

Source: NCBI Gene 388333 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_001394956

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35463
Approved symbol	SPDYE4
Name	speedy/RINGO cell cycle regulator family member E4
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183318
Ensembl biotype	protein_coding
OMIM	617628
Entrez	388333

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000328794, ENST00000580999, ENST00000582989, ENST00000688021, ENST00000689094

RefSeq mRNA: 2 — MANE Select: NM_001394956 NM_001128076, NM_001394956

CCDS: CCDS45609

Canonical transcript exons

ENST00000689094 — 7 exons

Exon	Start	End
ENSE00003519489	8753321	8753489
ENSE00003535902	8755520	8755605
ENSE00003637818	8756378	8756436
ENSE00003678364	8757262	8757492
ENSE00003926580	8750853	8752237
ENSE00003927706	8753094	8753197
ENSE00003936232	8758274	8758546

Expression profiles

Bgee: expression breadth broad, 69 present calls, max score 81.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0100 / max 11.2771, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164450	0.0050	3
164451	0.0050	2

Top tissues by expression

107 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	81.45	gold quality
left testis	UBERON:0004533	73.17	gold quality
testis	UBERON:0000473	72.85	gold quality
right testis	UBERON:0004534	71.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.96	gold quality
granulocyte	CL:0000094	52.27	gold quality
bone marrow cell	CL:0002092	44.05	gold quality
colonic epithelium	UBERON:0000397	43.49	silver quality
right coronary artery	UBERON:0001625	43.49	silver quality
monocyte	CL:0000576	42.75	gold quality
apex of heart	UBERON:0002098	42.68	silver quality
leukocyte	CL:0000738	42.49	gold quality
mucosa of stomach	UBERON:0001199	42.12	silver quality
blood	UBERON:0000178	40.36	silver quality
bone marrow	UBERON:0002371	40.31	silver quality
body of pancreas	UBERON:0001150	39.78	silver quality
fundus of stomach	UBERON:0001160	38.64	silver quality
liver	UBERON:0002107	38.50	silver quality
vermiform appendix	UBERON:0001154	38.21	gold quality
thoracic aorta	UBERON:0001515	38.21	gold quality
ascending aorta	UBERON:0001496	37.86	gold quality
right lobe of liver	UBERON:0001114	37.56	silver quality
pancreas	UBERON:0001264	37.02	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
descending thoracic aorta	UBERON:0002345	36.22	gold quality
mucosa of transverse colon	UBERON:0004991	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.12	silver quality
tonsil	UBERON:0002372	35.82	gold quality
ectocervix	UBERON:0012249	35.59	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

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), 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 E4 — A6NLX3 (reviewed: A6NLX3)

All UniProt accessions (3): A6NLX3, J3KT05, J3QR45

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Predominantly expressed in testis.

Similarity. Belongs to the Speedy/Ringo family.

RefSeq proteins (2): NP_001121548, NP_001381885* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020984	Speedy	Family
IPR057742	Speedy_E	Family

Pfam: PF11357

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NLX3-F1	78.37	0.55

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 5 (showing top): GOMF_KINASE_BINDING, BRUINS_UVC_RESPONSE_LATE, GSE14413_UNSTIM_VS_IFNB_STIM_RAW264_CELLS_UP, GSE5589_WT_VS_IL6_KO_LPS_STIM_MACROPHAGE_180MIN_DN, chr17p13

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

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

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
binding	1

Protein interactions and networks

STRING

316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPDYE4	CDRT15L2	A8MXV6	591
SPDYE4	C3orf22	Q8N5N4	581
SPDYE4	RNASE12	Q5GAN4	540
SPDYE4	C12orf56	Q8IXR9	527
SPDYE4	TBC1D28	Q2M2D7	515
SPDYE4	SMIM17	P0DL12	507
SPDYE4	SH2D7	A6NKC9	506
SPDYE4	SLC35G6	P0C7Q6	506
SPDYE4	SLC35G3	Q8N808	505
SPDYE4	C1orf167	Q5SNV9	505
SPDYE4	CC2D2B	Q6DHV5	505
SPDYE4	C22orf42	Q6IC83	495
SPDYE4	CCDC144A	A2RUR9	480
SPDYE4	ANKRD62	A6NC57	480
SPDYE4	OR3A2	P47893	477

IntAct

42 interactions, top by confidence:

A	B	Type	Score
SPDYE4	CKS1B	psi-mi:“MI:0915”(physical association)	0.670
SPDYE4	CDK5	psi-mi:“MI:0915”(physical association)	0.670
SPDYE4	GCK	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	QARS1	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	USP2	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	GPKOW	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	PPIL1	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	MAGOHB	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	TBC1D13	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	CDK3	psi-mi:“MI:0915”(physical association)	0.560
SPDYE4	BRD4	psi-mi:“MI:0915”(physical association)	0.540
SPDYE4	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
SPDYE4	SUPT5H	psi-mi:“MI:2364”(proximity)	0.270
GCK	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000
QARS1	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000
USP2	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000
GPKOW	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000
CKS1B	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000
CDK5	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000
PPIL1	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000
CDK3	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (71): SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), SPDYE4 (Two-hybrid), CDK3 (Two-hybrid), BRD4 (Affinity Capture-Western), SPDYE4 (Affinity Capture-Western), USP7 (Affinity Capture-MS), CDK2 (Affinity Capture-MS)

ESM2 similar proteins: A0A494C086, A0A494C0Z2, A0A494C191, A0JPH4, A6NHP3, A6NIY4, A6NJR5, A6NLX3, A6NNV3, A6QLI5, B0BNE4, O08918, O60543, O70302, O75916, P0CI01, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P24864, P39949, P49805, Q12967, Q495Y7, Q495Y8, Q4VXA5, Q4ZIN3, Q5IBH6, Q5IBH7, Q5MJ70, Q5SYB0, Q5XIQ2, Q5ZJR9, Q61457, Q6AYG1

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

727 predictions. Top by Δscore:

Variant	Effect	Δscore
17:8753485:GGTAG:G	acceptor_gain	1.0000
17:8753486:GTAG:G	acceptor_gain	1.0000
17:8753487:TAG:T	acceptor_gain	1.0000
17:8753488:AG:A	acceptor_gain	1.0000
17:8753489:GC:G	acceptor_loss	1.0000
17:8753490:C:CC	acceptor_gain	1.0000
17:8753490:C:T	acceptor_loss	1.0000
17:8753491:T:G	acceptor_loss	1.0000
17:8756372:CCTTA:C	donor_loss	1.0000
17:8756373:CTTA:C	donor_loss	1.0000
17:8756374:TTAC:T	donor_loss	1.0000
17:8756375:TACC:T	donor_loss	1.0000
17:8756376:A:C	donor_loss	1.0000
17:8756377:C:CG	donor_loss	1.0000
17:8757260:A:AC	donor_gain	1.0000
17:8757261:C:CC	donor_gain	1.0000
17:8757264:AGGAG:A	donor_gain	1.0000
17:8753317:CTAC:C	donor_loss	0.9900
17:8753318:TACC:T	donor_loss	0.9900
17:8753319:ACCT:A	donor_gain	0.9900
17:8753320:C:CT	donor_loss	0.9900
17:8753320:CCTC:C	donor_gain	0.9900
17:8753322:T:TA	donor_gain	0.9900
17:8753489:GCT:G	acceptor_gain	0.9900
17:8755606:C:CC	acceptor_gain	0.9900
17:8756376:A:AC	donor_gain	0.9900
17:8756377:C:CC	donor_gain	0.9900
17:8756433:TCCC:T	acceptor_gain	0.9900
17:8756434:CCC:C	acceptor_gain	0.9900
17:8756434:CCCC:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000397915 (17:8749502 G>C), RS1000467774 (17:8757934 C>T), RS1000647533 (17:8754878 G>A), RS1000682732 (17:8747693 C>T), RS1000740509 (17:8752604 A>G), RS1000933615 (17:8753443 C>T), RS1001094996 (17:8759753 G>A), RS1001268753 (17:8756111 G>A), RS1001367619 (17:8750410 A>T), RS1001600504 (17:8755849 T>C,G), RS1001800189 (17:8753963 T>A), RS1003174695 (17:8750939 T>C), RS1003353727 (17:8756329 C>T), RS1004270735 (17:8748818 A>G), RS1004361740 (17:8757563 C>A,G,T)

Disease associations

OMIM: gene MIM:617628 | 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
GCST005362_8	Attention deficit hyperactivity disorder	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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