SPDYC

Summary

SPDYC (speedy/RINGO cell cycle regulator family member C, HGNC:32681) is a protein-coding gene on chromosome 11q13.1, encoding Speedy protein C (Q5MJ68). Promotes progression through the cell cycle via binding and activation of CDK1 and CDK2.

Enables protein kinase binding activity. Predicted to be located in nucleus.

Source: NCBI Gene 387778 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 54 total
• GTEx eGene: eQTL in 4 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_001008778
• Notable: 54 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32681
Approved symbol	SPDYC
Name	speedy/RINGO cell cycle regulator family member C
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	Ringo2
Ensembl gene	ENSG00000204710
Ensembl biotype	protein_coding
OMIM	614030
Entrez	387778

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000377185

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000377185, ENST00000995354, ENST00000995355, ENST00001143809

RefSeq mRNA: 1 — MANE Select: NM_001008778 NM_001008778

CCDS: CCDS31606

Canonical transcript exons

ENST00000377185 — 7 exons

Exon	Start	End
ENSE00001473038	65173183	65173374
ENSE00001473039	65172684	65173014
ENSE00001473040	65172434	65172605
ENSE00001473042	65172246	65172331
ENSE00001473044	65171943	65172001
ENSE00001473046	65171327	65171499
ENSE00001473048	65170233	65170261

Expression profiles

Bgee: expression breadth broad, 45 present calls, max score 92.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2819 / max 78.6583, expressed in 88 samples.

Highest expression (Bgee): primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, lobe of liver, monocyte, leukocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SPDYC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	4.6e-64	+0.94	11:65170212:C:T
Lung	eqtl	7.5e-13	-0.48	11:65169248:A:C
Spleen	eqtl	4.4e-05	+0.61	11:65170212:C:T
Testis	eqtl	7.4e-03	-0.34	11:65370683:G:C
Testis	sqtl	3.3e-02	+0.93	11:65935886:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
115034	1.2819	88

Top tissues by expression

97 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.88	gold quality
right lobe of liver	UBERON:0001114	72.06	gold quality
monocyte	CL:0000576	68.90	gold quality
leukocyte	CL:0000738	68.27	gold quality
liver	UBERON:0002107	66.51	gold quality
blood	UBERON:0000178	57.24	gold quality
right testis	UBERON:0004534	49.29	gold quality
testis	UBERON:0000473	48.81	gold quality
left testis	UBERON:0004533	48.80	gold quality
placenta	UBERON:0001987	47.08	gold quality
granulocyte	CL:0000094	46.47	silver quality
bone marrow cell	CL:0002092	40.72	gold quality
skeletal muscle tissue	UBERON:0001134	40.67	silver quality
muscle tissue	UBERON:0002385	38.87	silver quality
gall bladder	UBERON:0002110	37.35	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
sural nerve	UBERON:0015488	36.89	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
mucosa of transverse colon	UBERON:0004991	36.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.93	gold quality
muscle of leg	UBERON:0001383	35.87	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
gastrocnemius	UBERON:0001388	35.00	silver quality
tonsil	UBERON:0002372	34.30	gold quality
spleen	UBERON:0002106	34.20	silver quality
lymph node	UBERON:0000029	34.13	silver quality
upper lobe of left lung	UBERON:0008952	34.06	gold quality
smooth muscle tissue	UBERON:0001135	33.84	gold quality
body of pancreas	UBERON:0001150	33.76	gold quality
duodenum	UBERON:0002114	33.27	silver quality
metanephros cortex	UBERON:0010533	33.20	silver quality
vermiform appendix	UBERON:0001154	33.10	silver quality
fallopian tube	UBERON:0003889	32.82	silver quality
kidney	UBERON:0002113	32.77	gold quality
Ammon’s horn	UBERON:0001954	32.66	silver quality
right uterine tube	UBERON:0001302	32.59	gold quality
rectum	UBERON:0001052	32.50	silver quality
lung	UBERON:0002048	32.33	gold quality
adult mammalian kidney	UBERON:0000082	32.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	32.07	silver quality
substantia nigra	UBERON:0002038	31.83	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	31.59	gold quality
multicellular organism	UBERON:0000468	31.51	gold quality
primary visual cortex	UBERON:0002436	31.48	gold quality
anterior cingulate cortex	UBERON:0009835	31.46	gold quality
cerebral cortex	UBERON:0000956	31.06	silver quality
frontal cortex	UBERON:0001870	30.59	silver quality
right ovary	UBERON:0002118	30.57	silver quality
cortex of kidney	UBERON:0001225	30.54	gold quality
tibial nerve	UBERON:0001323	30.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	30.18	gold quality
brain	UBERON:0000955	30.11	silver quality
right adrenal gland	UBERON:0001233	29.88	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
heart left ventricle	UBERON:0002084	29.51	silver quality
endometrium	UBERON:0001295	29.25	gold quality
right lung	UBERON:0002167	28.89	silver quality
right adrenal gland cortex	UBERON:0035827	28.51	silver quality
right coronary artery	UBERON:0001625	27.45	gold quality
superior frontal gyrus	UBERON:0002661	27.17	gold quality
esophagus mucosa	UBERON:0002469	26.98	gold quality
thoracic mammary gland	UBERON:0005200	26.97	gold quality
right frontal lobe	UBERON:0002810	26.72	gold quality
ectocervix	UBERON:0012249	26.68	gold quality
saliva-secreting gland	UBERON:0001044	26.21	gold quality
body of uterus	UBERON:0009853	26.13	gold quality
esophagus	UBERON:0001043	26.10	gold quality
prostate gland	UBERON:0002367	25.94	gold quality
right atrium auricular region	UBERON:0006631	25.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	25.80	gold quality
left coronary artery	UBERON:0001626	25.72	gold quality
calcaneal tendon	UBERON:0003701	25.55	gold quality
popliteal artery	UBERON:0002250	25.48	gold quality
tibial artery	UBERON:0007610	25.44	gold quality
descending thoracic aorta	UBERON:0002345	25.32	gold quality
minor salivary gland	UBERON:0001830	25.21	gold quality
left uterine tube	UBERON:0001303	24.91	gold quality
lower esophagus	UBERON:0013473	24.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	24.77	gold quality
vagina	UBERON:0000996	24.73	gold quality
omental fat pad	UBERON:0010414	24.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	23.94	gold quality
zone of skin	UBERON:0000014	23.67	silver quality
skin of leg	UBERON:0001511	23.46	silver quality
skin of abdomen	UBERON:0001416	23.38	gold quality
corpus callosum	UBERON:0002336	23.24	gold quality
thoracic aorta	UBERON:0001515	23.02	gold quality
ascending aorta	UBERON:0001496	22.96	gold quality
left adrenal gland cortex	UBERON:0035825	22.37	gold quality
pituitary gland	UBERON:0000007	22.27	gold quality
lower esophagus mucosa	UBERON:0035834	22.15	gold quality
adrenal tissue	UBERON:0018303	21.49	gold quality
apex of heart	UBERON:0002098	20.28	gold quality
mucosa of stomach	UBERON:0001199	18.29	gold quality
adenohypophysis	UBERON:0002196	15.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	69.02
E-ANND-3	no	1.48

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 69 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Olfactory bulb	tissue	5.3
Cerebellum	tissue	5.1	medium
Cerebral cortex	tissue	4.5	medium
Insular cortex	tissue	4.5
Amygdala	tissue	4.0
Retrosplenial cortex	tissue	3.7
Cingulate cortex	tissue	3.6
Temporal cortex	tissue	3.6
Basal ganglia	tissue	3.5	medium
Hippocampal formation	tissue	3.5
Entorhinal cortex	tissue	3.5
Ventral pallidum	tissue	3.3
Occipital cortex	tissue	3.3
Prefrontal cortex	tissue	3.2
Putamen	tissue	3.2
Corpus callosum	tissue	3.1
Motor cortex	tissue	3.0
Somatosensory cortex	tissue	3.0
Periaqueductal gray	tissue	2.9
Septum	tissue	2.9
Hypothalamus	tissue	2.7
Liver	tissue	2.6	medium
Spinal cord	tissue	2.5
Midbrain	tissue	2.4
Medulla oblongata	tissue	2.3
Substantia nigra	tissue	2.2
Superior colliculi	tissue	2.1
Pons	tissue	1.9
Thalamus	tissue	1.9
Testis	tissue	0.7	high
Epididymis	tissue	0.3	medium
Nucleus accumbens	tissue	0.3
Locus coeruleus	tissue	0.3
Hippocampus	tissue	0.3	medium
Skeletal muscle	tissue	0.2	not detected
Choroid plexus	tissue	0.2
Postcentral gyrus	tissue	0.2
Ovary	tissue	0.1	not detected
Placenta	tissue	0.1	medium
Small intestine	tissue	0.1	high
Gallbladder	tissue	0.1	high
Cervix	tissue	0.0	medium
Lymph node	tissue	0.0	medium
Breast	tissue	0.0	medium
Stomach 1	tissue	0.0	high
Heart muscle	tissue	0.0	medium
Vagina	tissue	0.0	low
Seminal vesicle	tissue	0.0	medium
Esophagus	tissue	0.0	low
Salivary gland	tissue	0.0	high
Rectum	tissue	0.0	high
Parathyroid gland	tissue	0.0	high
Colon	tissue	0.0	high
Urinary bladder	tissue	0.0	medium
Pancreas	tissue	0.0	high
Endometrium 1	tissue	0.0	high
Thyroid gland	tissue	0.0	high
Lung	tissue	0.0	high
Kidney	tissue	0.0	high
Duodenum	tissue	0.0	high

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Subiculum (3.2), Ventral hippocampus (3.1), White matter (3.1), Dorsal hippocampus (2.7), Ventral spinal cord (2.5).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 2.62e-07, LOEUF 1.07, missense Z 0.701 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000377185 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 2)

• CDK-Speedy/Ringo C complexes positively regulate cell cycle progression during the late S and G(2) phases of the cell cycle. (PMID:18802405)
• Results indicate a role for RINGO C in the mitotic checkpoint, which might be mediated by defective recruitment of SAC components and deregulation of the activity of Aurora kinase B. (PMID:20605920)

Cross-species orthologs

0 orthologs

Paralogs (1): SPDYA (ENSG00000163806)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mus musculus	Q5IBH7	90.7%	Diamond
Rattus norvegicus	Q8R496	90.7%	Diamond
Xenopus laevis	Q9PU13	88.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR6751	ncRNA	102465449
SYVN1	protein-coding	84447
POLA2	protein-coding	23649
CAPN1-AS1	ncRNA	728975
CAPN1	protein-coding	823

Protein

Protein identifiers

Speedy protein C — Q5MJ68 (reviewed: Q5MJ68)

Alternative names: Rapid inducer of G2/M progression in oocytes C

All UniProt accessions (1): Q5MJ68

UniProt curated annotations — full annotation on UniProt →

Function. Promotes progression through the cell cycle via binding and activation of CDK1 and CDK2. Involved in the spindle-assembly checkpoint. Required for recruitment of MAD2L1, BUBR1 and BUB1 to kinetochores. Required for the correct localization of the active form of Aurora B in prometaphase.

Subunit / interactions. Interacts with CDK1 and CDK2. Interacts with AURKB.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in a variety of tissues including bone marrow, kidney, small intestine, liver, placenta and testis.

Domain organisation. The C-terminus is required for CDK2-activation, but not CDK2-binding.

Similarity. Belongs to the Speedy/Ringo family.

RefSeq proteins (1): NP_001008778* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020984	Speedy	Family
IPR052316	Speedy-Ringo_regulator	Family

Pfam: PF11357

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

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5MJ68-F1	75.94	0.49

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 10 (showing top): chr11q13, KEGG_OOCYTE_MEIOSIS, GOMF_KINASE_BINDING, MARTENS_TRETINOIN_RESPONSE_UP, DACH1_TARGET_GENES, ZNF592_TARGET_GENES, KEGG_PROGESTERONE_MEDIATED_OOCYTE_MATURATION, HAY_BONE_MARROW_PLATELET, GTF2A2_TARGET_GENES, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN

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 (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

10 GO namespaces:

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
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 5 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
protein kinase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 398 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPDYC	GARIN5B	Q8N5Q1	599
SPDYC	OR4K5	Q8NGD3	555
SPDYC	ARMC9	Q7Z3E5	480
SPDYC	ZNF687	Q8N1G0	478
SPDYC	ITPRIP	Q8IWB1	468
SPDYC	HSPBAP1	Q96EW2	468
SPDYC	CATSPER4	Q7RTX7	451
SPDYC	ADGRA3	Q8IWK6	444
SPDYC	TTBK1	Q5TCY1	428
SPDYC	OR5H1	A6NKK0	420
SPDYC	NPAT	Q14207	404
SPDYC	NUP210L	Q5VU65	391
SPDYC	CMTM3	Q96MX0	391
SPDYC	BTBD18	B2RXH4	389
SPDYC	ACSM4	P0C7M7	388

IntAct

Human interaction partners of SPDYC in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
ARPP19	physical association	0.560	3
FCF1	physical association	0.560	3
LZTS1	physical association	0.560	3
PAX6	physical association	0.560	3
CDK1	association	0.530	1
RBFOX3	association	0.350	1

BioGRID (14 interactions; top human partners by supporting records): CDK1 (Affinity Capture-MS; 2 records), CDK2 (Affinity Capture-MS; 2 records), ARPP19 (Two-hybrid), CDKN1B (Affinity Capture-Western), CKS1B (Affinity Capture-MS), CKS2 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), FCF1 (Two-hybrid), HERC1 (Affinity Capture-MS), LZTS1 (Two-hybrid), PAX6 (Two-hybrid), RBFOX3 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for SPDYC: 54 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	6
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 706):

Position(s)	Effect	Δscore	Sites
11:65171997	donor_gain	1.0000
11:65172244–65172245	acceptor_loss	1.0000	6
11:65171936	acceptor_gain	0.9900
11:65172002–65172003	donor_loss	0.9900	5
11:65172332–65172333	donor_loss	0.9900	5
11:65171941–65171942	acceptor_loss	0.9800	6
11:65172333	donor_loss	0.9800
11:65172336	donor_loss	0.9800
11:65171358	donor_gain	0.9700
11:65172241	acceptor_gain	0.9700

AlphaMissense

483 missense substitutions predicted likely pathogenic (of 1,916 scored), across 106 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M159	9	0.884	0.970
M174	9	0.857	0.973
D78	8	0.965	0.980
D85	8	0.962	0.993
F96	8	0.954	0.990
D120	8	0.944	0.971
F112	8	0.936	0.988
F148	8	0.926	0.992
D124	8	0.924	0.975
F74	8	0.918	0.993
F133	8	0.897	0.984
M121	8	0.888	0.941
H191	8	0.877	0.949
M91	8	0.873	0.941
H180	8	0.818	0.948
W183	7	0.972	0.994
W156	7	0.953	0.986
F161	7	0.953	0.992
W135	7	0.952	0.979
F62	7	0.951	0.984

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Breast Invasive Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (TCGA)	unfavorable	6.77e-05
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000846

Disease associations

OMIM: gene MIM:614030 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
decabromobiphenyl ether	affects expression	1
sodium arsenite	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Cyclosporine	decreases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.