CYCS

Summary

CYCS (cytochrome c, somatic, HGNC:19986) is a protein-coding gene on chromosome 7p15.3, encoding Cytochrome c (P99999). Electron carrier protein. It is a common-essential gene (DepMap: required in 91.6% of cancer cell lines).

This gene encodes a small heme protein that functions as a central component of the electron transport chain in mitochondria. The encoded protein associates with the inner membrane of the mitochondrion where it accepts electrons from cytochrome b and transfers them to the cytochrome oxidase complex. This protein is also involved in initiation of apoptosis. Mutations in this gene are associated with autosomal dominant nonsyndromic thrombocytopenia. Numerous processed pseudogenes of this gene are found throughout the human genome.

Source: NCBI Gene 54205 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombocytopenia 4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 65 total — 2 pathogenic, 4 likely-pathogenic
• GTEx eGene: eQTL in 11 tissues, sQTL in 14 (q < 0.05)
• Phenotypes (HPO): 3
• Cancer dependency (DepMap): dependent in 91.6% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.34 (highly constrained)
• MANE Select transcript: NM_018947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19986
Approved symbol	CYCS
Name	cytochrome c, somatic
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	HCS, CYC
Ensembl gene	ENSG00000172115
Ensembl biotype	protein_coding
OMIM	123970
Entrez	54205

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 2 nonsense_mediated_decay

MANE Select: ENST00000305786

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 3

ENST00000305786, ENST00000409409, ENST00000409764, ENST00000413447, ENST00000877224, ENST00000877225, ENST00000877226, ENST00000877227, ENST00000912017, ENST00000912018, ENST00000962279, ENST00001097490, ENST00001097491, ENST00001097492, ENST00001097493, ENST00001097494, ENST00001097495, ENST00001097496, ENST00001097497, ENST00001139687

RefSeq mRNA: 1 — MANE Select: NM_018947 NM_018947

CCDS: CCDS5393

Canonical transcript exons

ENST00000305786 — 3 exons

Exon	Start	End
ENSE00001147465	25123951	25124127
ENSE00001207041	25118656	25123849
ENSE00001584587	25125200	25125260

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.7320 / max 2038.7012, expressed in 1819 samples.

Highest expression (Bgee): mucosa of transverse colon, rectum, atrium auricular region, hindlimb stylopod muscle, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CYCS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	sqtl	5.3e-13	-0.93	7:25179582:A:T
Colon Transverse	eqtl	2.0e-11	+0.12	7:25148507:G:C
Thyroid	sqtl	3.1e-08	-0.74	7:25179582:A:T
Lung	sqtl	5.5e-08	-0.80	7:25124125:A:C
Adipose Visceral Omentum	sqtl	1.6e-07	-0.80	7:25124125:A:C
Esophagus Muscularis	sqtl	1.7e-06	-0.73	7:25124125:A:C
Adipose Subcutaneous	sqtl	2.1e-06	-0.71	7:25124125:A:C
Skin Sun Exposed Lower leg	sqtl	8.1e-06	-0.63	7:25124125:A:C
Brain Putamen basal ganglia	sqtl	3.8e-04	-1.03	7:25149993:C:T
Brain Cerebellar Hemisphere	eqtl	7.3e-04	+0.42	7:25220933:T:C
Colon Sigmoid	sqtl	9.9e-04	-0.74	7:25038460:A:G
Artery Aorta	sqtl	1.8e-03	-0.66	7:25124125:A:C
Artery Coronary	eqtl	5.2e-03	+0.92	7:25057301:G:A
Bladder	eqtl	6.4e-03	+2.39	7:25763978:G:A
Artery Coronary	sqtl	9.4e-03	+0.92	7:25149993:C:T
Stomach	eqtl	1.0e-02	+0.47	7:24230412:A:G
Thyroid	eqtl	1.1e-02	-0.13	7:25448908:G:A
Brain Frontal Cortex BA9	sqtl	1.5e-02	+2.59	7:25514582:G:A
Breast Mammary Tissue	sqtl	1.5e-02	-0.69	7:25124125:A:C
Pituitary	eqtl	1.9e-02	+1.54	7:24644717:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
83156	77.0616	1819
83157	3.6704	1446

Top tissues by expression

showing 100 of 261 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.16	gold quality
rectum	UBERON:0001052	99.08	gold quality
right atrium auricular region	UBERON:0006631	99.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.91	gold quality
gastrocnemius	UBERON:0001388	98.52	gold quality
muscle of leg	UBERON:0001383	98.39	gold quality
cardiac atrium	UBERON:0002081	98.34	gold quality
prefrontal cortex	UBERON:0000451	98.22	gold quality
apex of heart	UBERON:0002098	98.21	gold quality
colonic epithelium	UBERON:0000397	98.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.94	gold quality
heart left ventricle	UBERON:0002084	97.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.92	gold quality
transverse colon	UBERON:0001157	97.90	gold quality
anterior cingulate cortex	UBERON:0009835	97.87	gold quality
cortical plate	UBERON:0005343	97.80	gold quality
smooth muscle tissue	UBERON:0001135	97.67	gold quality
vermiform appendix	UBERON:0001154	97.63	gold quality
cardiac ventricle	UBERON:0002082	97.53	gold quality
islet of Langerhans	UBERON:0000006	97.23	gold quality
right frontal lobe	UBERON:0002810	97.20	gold quality
embryo	UBERON:0000922	97.13	gold quality
ganglionic eminence	UBERON:0004023	97.13	gold quality
heart	UBERON:0000948	97.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.78	gold quality
ventricular zone	UBERON:0003053	96.76	gold quality
monocyte	CL:0000576	96.65	gold quality
hypothalamus	UBERON:0001898	96.43	gold quality
leukocyte	CL:0000738	96.42	gold quality
caudate nucleus	UBERON:0001873	96.32	gold quality
body of stomach	UBERON:0001161	96.30	gold quality
metanephros cortex	UBERON:0010533	96.00	gold quality
esophagus mucosa	UBERON:0002469	95.92	gold quality
amygdala	UBERON:0001876	95.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.90	gold quality
skeletal muscle organ	UBERON:0014892	95.75	gold quality
bone marrow cell	CL:0002092	95.68	gold quality
nucleus accumbens	UBERON:0001882	95.67	gold quality
neocortex	UBERON:0001950	95.62	gold quality
putamen	UBERON:0001874	95.57	gold quality
calcaneal tendon	UBERON:0003701	95.57	gold quality
left testis	UBERON:0004533	95.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.55	gold quality
gall bladder	UBERON:0002110	95.54	gold quality
cerebellar cortex	UBERON:0002129	95.54	gold quality
omental fat pad	UBERON:0010414	95.53	gold quality
esophagus	UBERON:0001043	95.52	gold quality
cerebellar hemisphere	UBERON:0002245	95.50	gold quality
right testis	UBERON:0004534	95.50	gold quality
left adrenal gland cortex	UBERON:0035825	95.49	gold quality
popliteal artery	UBERON:0002250	95.48	gold quality
tibial artery	UBERON:0007610	95.47	gold quality
peritoneum	UBERON:0002358	95.45	gold quality
left adrenal gland	UBERON:0001234	95.42	gold quality
frontal cortex	UBERON:0001870	95.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.27	gold quality
right adrenal gland	UBERON:0001233	95.24	gold quality
lower esophagus	UBERON:0013473	95.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.17	gold quality
adrenal tissue	UBERON:0018303	95.15	gold quality
artery	UBERON:0001637	95.12	gold quality
left uterine tube	UBERON:0001303	95.01	gold quality
adrenal cortex	UBERON:0001235	95.00	gold quality
colon	UBERON:0001155	94.97	gold quality
adenohypophysis	UBERON:0002196	94.97	gold quality
adrenal gland	UBERON:0002369	94.97	gold quality
right adrenal gland cortex	UBERON:0035827	94.87	gold quality
lower esophagus mucosa	UBERON:0035834	94.84	gold quality
spinal cord	UBERON:0002240	94.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.78	gold quality
left coronary artery	UBERON:0001626	94.74	gold quality
stomach	UBERON:0000945	94.73	gold quality
cerebellum	UBERON:0002037	94.69	gold quality
aorta	UBERON:0000947	94.64	gold quality
large intestine	UBERON:0000059	94.31	gold quality
intestine	UBERON:0000160	94.26	gold quality
right lobe of liver	UBERON:0001114	94.26	gold quality
minor salivary gland	UBERON:0001830	94.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.20	gold quality
adult mammalian kidney	UBERON:0000082	94.18	gold quality
stromal cell of endometrium	CL:0002255	94.09	gold quality
mucosa of stomach	UBERON:0001199	94.08	gold quality
upper lobe of left lung	UBERON:0008952	94.08	gold quality
telencephalon	UBERON:0001893	94.01	gold quality
cerebral cortex	UBERON:0000956	93.98	gold quality
small intestine	UBERON:0002108	93.97	gold quality
forebrain	UBERON:0001890	93.93	gold quality
ascending aorta	UBERON:0001496	93.89	gold quality
thoracic aorta	UBERON:0001515	93.81	gold quality
coronary artery	UBERON:0001621	93.80	gold quality
brain	UBERON:0000955	93.78	gold quality
left lobe of thyroid gland	UBERON:0001120	93.75	gold quality
right lobe of thyroid gland	UBERON:0001119	93.62	gold quality
substantia nigra	UBERON:0002038	93.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.31	gold quality
testis	UBERON:0000473	93.29	gold quality
ectocervix	UBERON:0012249	93.28	gold quality
lymph node	UBERON:0000029	93.17	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	1218.54
E-HCAD-8	yes	1139.34
E-MTAB-8410	yes	22.34
E-CURD-122	yes	21.79
E-CURD-88	yes	18.75
E-MTAB-6701	yes	8.85
E-MTAB-7316	yes	7.98
E-MTAB-8271	yes	6.72
E-CURD-89	no	1614.90
E-HCAD-5	no	1413.55
E-MTAB-8060	no	629.62
E-GEOD-125970	no	15.85
E-CURD-46	no	11.28
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	746.5
Skeletal muscle	tissue	453.4	medium
Heart muscle	tissue	446.3	medium
Colon	tissue	246.8	high
Rectum	tissue	224.2	high
Parathyroid gland	tissue	212.0	high
Kidney	tissue	152.7	high
Postcentral gyrus	tissue	146.9
Retina	tissue	142.6
Duodenum	tissue	141.2	high
Choroid plexus	tissue	121.9
Small intestine	tissue	113.0	high
Urinary bladder	tissue	111.7	high
Adrenal gland	tissue	108.9	medium
Liver	tissue	108.0	medium
Stomach 1	tissue	101.9	high
Esophagus	tissue	88.0	medium
Smooth muscle	tissue	85.0	medium
Appendix	tissue	84.2	high
Tonsil	tissue	83.7	medium
Adipose tissue	tissue	80.6	low
Bone marrow	tissue	80.1	high
Locus coeruleus	tissue	78.2
Hippocampus	tissue	75.7	medium
Nucleus accumbens	tissue	73.0
Thyroid gland	tissue	69.8	medium
Thymus	tissue	68.9
Lymph node	tissue	59.6	high
Seminal vesicle	tissue	56.6	high
Breast	tissue	55.4	high
Testis	tissue	55.3	high
Salivary gland	tissue	54.6	high
Vagina	tissue	54.1	medium
Prostate	tissue	50.9	high
Pituitary gland	tissue	50.0
Gallbladder	tissue	49.6	high
Spleen	tissue	45.2	low
Lung	tissue	43.3	high
Cervix	tissue	42.5	medium
Placenta	tissue	40.4	high
Fallopian tube	tissue	40.4	medium
Endometrium 1	tissue	39.5	medium
Epididymis	tissue	39.1	medium
Pancreas	tissue	36.4	high
Ovary	tissue	34.9	low
Skin 1	tissue	30.1	high
Cerebral cortex	tissue	0.5	medium
Ventral pallidum	tissue	0.5
Cingulate cortex	tissue	0.5
Periaqueductal gray	tissue	0.5
Basal ganglia	tissue	0.3	medium
Substantia nigra	tissue	0.3
Olfactory bulb	tissue	0.3
Septum	tissue	0.3
Retrosplenial cortex	tissue	0.3
Temporal cortex	tissue	0.3
Thalamus	tissue	0.2
Cerebellum	tissue	0.2	medium
Hippocampal formation	tissue	0.2
Insular cortex	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Lateral geniculate body (110.7), Mammillary body (110.6), Cerebellar nuclei (103.9), Pulvinar (103.0), Precentral gyrus, middle (102.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CREB1, CTNNB1, ESRRA, NRF1, PPARGC1A, PRKAA1, SP1, TCF7L2

miRNA regulators (miRDB)

Targeting CYCS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 163 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Functional genomics

gnomAD constraint: pLI 0.977, LOEUF 0.335, missense Z 1.38 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000305786 — one region, missense o/e 0.69. DepMap (CRISPR cell-line fitness): dependent in 91.6% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OCUM-1 (-2.122), L-363 (-2.061), HCC1187 (-1.997), COR-L311 (-1.987), A-375 (-1.966), SNU-869 (-1.85), SU-DHL-4 (-1.832), RI-1 (-1.821), MOLM-13 (-1.815), MJ (-1.8), SLR 20 (-1.786), HCC-461 (-1.775), SNU-5 (-1.767), U-937 (-1.756), CFPAC-1 (-1.75).

Literature-anchored findings (GeneRIF, showing 40)

• galectin-3 is enriched in the mitochondria and prevents mitochondrial damage and cytochrome c release (PMID:11839755)
• non-rare allelic variants of the Cyt c protein are absent in the populations analyzed in this study (PMID:16934433)
• Mutation of human cytochrome c enhances the intrinsic apoptotic pathway and causes thrombocytopenia (PMID:18345000)
• MICS1 individually functions in mitochondrial morphology and cytochrome c release. (PMID:18417609)
• Serum cyto-c is a potent tumor marker as a predictor for malignant potential in several different types of cancer. (PMID:18825408)
• Both neurons and cancer cells strictly inhibit cytochrome c-mediated apoptosis by a mechanism dependent on glucose metabolism. (PMID:19029908)
• In 77 Italian patients with inherited thrombocytopenia and clinical and laboratory features similar to those of patients with the CYCS missense (Gly41Ser) mutation, no alterations of the open reading frame were identified. (PMID:19172527)
• there was no evidence of somatic mutations of CYTOCHROME C in the cancers (PMID:19404857)
• No difference in the serum level of cytochrome c was seen among the the groups of patients with type 2 diabetes, controls or in subjects with IGT. (PMID:19640329)
• Data show that sorafenib initiated lethal apoptotic process through the release of cytochrome c and caspase 3/7 activation. (PMID:19770576)
• Serum LRG when bound to extracellular Cyt c that is released from apoptotic cells acts as a survival factor for lymphocytes and possibly other cells that are susceptible to the toxic effect of extracellular Cyt c. (PMID:19851871)
• Membrane-associated XIAP induces mitochondrial outer membrane permeabilization leading to cytochrome c and Smac release, which is dependent on Bax and Bak. (PMID:19875445)
• NOA36/ZNF330 is translocated from the mitochondria to the cytoplasm when apoptosis is induced and that it contributes to cytochrome c release. (PMID:19895853)
• it is the specific nitration of solvent-exposed Tyr74 which enhances the peroxidase activity and blocks the ability of cytochrome c to activate caspase-9, thereby preventing the apoptosis signaling pathway (PMID:20227384)
• heme electronic structure change may ultimately be responsible for the enhanced proapoptotic activity of G41S mutated human cyt c (PMID:21192676)
• Cerebrospinal fluid Bcl-2 and cytochrome C levels are elevated in adults after severe traumatic brain injury. (PMID:21448217)
• Tyrosine phosphorylation turns alkaline transition into a biologically relevant process and makes human cytochrome c behave as an anti-apoptotic switch. (PMID:21706253)
• Resveratrol induces p53-independent, X-linked inhibitor of apoptosis protein (XIAP)-mediated Bax protein oligomerization on mitochondria to initiate cytochrome c release and caspase activation. (PMID:21712378)
• Data show that G-Rh2 and Bet A cooperated to induce Bax traslocation to mitochondria and cytochrome c release, and enhanced cleavage of caspase-8 and Bid. (PMID:21751259)
• Translocation of ARTS initiates a first wave of caspase activation leading to the subsequent release of additional mitochondrial factors, including cytochrome C and SMAC/Diablo. (PMID:21869827)
• Studies indicate that the CYCS mutation in TP Cargeegis a glycine 41 replacement by serine, which yields a cytochrome C variant with enhanced apoptotic pathway activity in vitro. (PMID:22102269)
• mitochondrial import and direct electron transfer from cytochrome c to Rac1 modulates mitochondrial H(2)O(2) production in alveolar macrophages pulmonary fibrosis. (PMID:22157762)
• Dynamic changes in cytochrome c distribution at the Raman band of 750 cm(-1) were observed after adding an apoptosis inducer to the cells. (PMID:22184220)
• Specific nitration of tyrosines 46 and 48 makes cytochrome c assemble a non-functional apoptosome. (PMID:22192356)
• The levels of cellular apoptosis-associated proteins such as Smac/DIABLO, Cyto C, and the activated fragment of caspase-3 increased in pancreatic cancer cells, but the expression of XIAP was significantly decreased after 24 h treatment with the combination of TRAIL and gemcitabine. (PMID:22320973)
• CCN1 promotes the activation of p53 and p38 MAPK, which mediate enhanced cytochrome c release to amplify the cytotoxicity of TNFalpha. (PMID:22363611)
• structural characterization of cytochrome c in micelle (PMID:23070294)
• Spectroscopic analyses of HCCS alone and complexes of HCCS with site-directed variants of cytochrome c revealed the fundamental steps of heme attachment and maturation. (PMID:23150584)
• Data indicate that the formation of cytochrome c-Apaf-1 apoptosome and the presence of Smac are absolutely required for PSAP-induced apoptosis. (PMID:23207240)
• results suggest the impact of residue 41 on the conformation of cytochrome c influences its ability to act in both of its physiological roles, electron transport and caspase activation (PMID:23334161)
• G-Rh2 causes rapid and dramatic translocation of both Bak and Bax, which subsequently triggers mitochondrial cytochrome c release and consequent caspase activation. (PMID:23443079)
• a mechanism of multiple radical formations in the cytochrome c-phospholipid complexes under H2O2 treatment, consistent with the stabilization of the radical in the G41S mutant, which elicits a greater peroxidase activity from cytochrome c (PMID:24099549)
• Data indicate a novel missense mutation (Y48H) of the cytochrome c (CYCS) gene responsible for thrombocytopenia. (PMID:24326104)
• proposed that mutation of residue 41, and interaction with cardiolipin, increase peroxidase activity by altering the 40-57 Omega loop and its hydrogen bond network with the propionate of haem ring A; these changes enhance access of hydrogen peroxide and substrate to the haem (PMID:24329121)
• In vitro ultrastructural changes of MCF-7 for metastasise bone cancer and induction of apoptosis via mitochondrial cytochrome C released by CaCO3/Dox nanocrystals (PMID:25028650)
• The mitochondrial metalloprotease OMA1 was activated in a Bax- and Bak-dependent fashion. (PMID:25275009)
• Monitoring of serum cytochrome c might also serve as a sensitive apoptotic marker in vivo reflecting chemotherapy-induced cell death burden in patients with non-small cell lung cancer. (PMID:25578497)
• These findings establish a framework for understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF-Ibeta. (PMID:26216969)
• This work reveals a direct conformational link between the 40-57 Omega-loop of cytochrome c in which residue 41 resides and the dynamical properties of the axial ligand to the heme iron. (PMID:27461282)
• ROCK activation phosphorylated Rac1b at Ser71 and increased reactive oxygen species (ROS) levels by facilitating the interaction between Rac1b and cytochrome c. Conversely, ROCK inactivation abolished their interaction, concomitant with ROS reduction. (PMID:28317242)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm10053	ENSMUSG00000058927
mus_musculus	Cycs	ENSMUSG00000063694
rattus_norvegicus	Cycs	ENSRNOG00000010452
rattus_norvegicus	Cycsl2	ENSRNOG00000033559
rattus_norvegicus	Cycs-ps9	ENSRNOG00000065095
drosophila_melanogaster	Cyt-c-d	FBGN0086907
caenorhabditis_elegans		WBGENE00013854
caenorhabditis_elegans		WBGENE00017121

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88578) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal apoptosis	1
decreased embryo size	1
abnormal extraembryonic tissue morphology	1
embryonic growth retardation	1
abnormal cellular respiration	1
embryonic lethality during organogenesis, complete penetrance	1

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
Oryza sativa Indica Group	A2Y4S9	100.0%	Diamond
Macaca mulatta	P00002	100.0%	Diamond
Cereibacter sphaeroides	P0C0X8	100.0%	Diamond
Brassica napus	P62772	100.0%	Diamond
Brassica oleracea	P62773	100.0%	Diamond
Bos taurus	P62894	100.0%	Diamond
Sus scrofa	P62895	100.0%	Diamond
Ovis aries	P62896	100.0%	Diamond
Gallus gallus	P67881	100.0%	Diamond
Meleagris gallopavo	P67882	100.0%	Diamond
Equus quagga burchellii	P68096	100.0%	Diamond
Equus asinus	P68097	100.0%	Diamond
Lama guanicoe	P68098	100.0%	Diamond
Camelus dromedarius	P68099	100.0%	Diamond
Eschrichtius robustus	P68100	100.0%	Diamond
Crotalus adamanteus	P68517	100.0%	Diamond
Crotalus atrox	P68518	100.0%	Diamond
Crotalus viridis viridis	P68519	100.0%	Diamond
Ceratitis capitata	P84030	100.0%	Diamond
Pan troglodytes	P99998	100.0%	Diamond
Oryza sativa Japonica Group	Q0DI31	100.0%	Diamond
Cereibacter sphaeroides 2.4.1	Q3J164	100.0%	Diamond
Macaca sylvanus	Q52V08	100.0%	Diamond
Pongo abelii	Q5RFH4	100.0%	Diamond
Gorilla gorilla gorilla	Q6WUX8	100.0%	Diamond
Haematobia irritans	P00035	99.1%	Diamond
Lucilia cuprina	P00036	99.1%	Diamond
Equus caballus	P00004	99.0%	Diamond
Canis lupus familiaris	P00011	99.0%	Diamond
Mirounga leonina	P00012	99.0%	Diamond
Dromaius novaehollandiae	P00018	99.0%	Diamond
Struthio camelus	P00019	99.0%	Diamond
Cephalopachus bancanus	Q52V09	99.0%	Diamond
Rickettsia felis Marseille-URRWFXCal2	Q4UKP6	98.3%	Diamond
Rickettsia conorii str. Malish 7	Q92IT3	98.3%	Diamond
Oryctolagus cuniculus	P00008	98.1%	Diamond
Aptenodytes patagonicus	P00017	98.1%	Diamond
Katsuwonus pelamis	P00025	98.1%	Diamond
Thunnus alalunga	P81459	98.1%	Diamond
Trachypithecus cristatus	Q7YR71	98.1%	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
SPMIP4	protein-coding	136895
GSDME	protein-coding	1687
OSBPL3	protein-coding	26031
PALS2	protein-coding	51678
NPVF	protein-coding	64111

Protein

Protein identifiers

Cytochrome c — P99999 (reviewed: P99999)

All UniProt accessions (3): C9JFR7, P99999, G4XXL9

UniProt curated annotations — full annotation on UniProt →

Function. Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases.

Subcellular location. Mitochondrion intermembrane space.

Post-translational modifications. Binds 1 heme c group covalently per subunit. Phosphorylation at Tyr-49 and Tyr-98 both reduce by half the turnover in the reaction with cytochrome c oxidase, down-regulating mitochondrial respiration.

Disease relevance. Thrombocytopenia 4 (THC4) [MIM:612004] A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the cytochrome c family.

RefSeq proteins (1): NP_061820* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002327	Cyt_c_1A/1B	Family
IPR009056	Cyt_c-like_dom	Domain
IPR036909	Cyt_c-like_dom_sf	Homologous_superfamily

Pfam: PF00034

UniProt features (36 total): modified residue 7, helix 7, mutagenesis site 6, binding site 4, sequence variant 3, strand 3, sequence conflict 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

13 structures by resolution:

PDB	Title	Method	Resolution (Å)
5TY3	Crystal structure of K72A variant of Human Cytochrome c	X-RAY DIFFRACTION	1.25
3ZOO	Structure of the Y46F mutant of human cytochrome c	X-RAY DIFFRACTION	1.35
5O10	Y48H mutant of human cytochrome c	X-RAY DIFFRACTION	1.36
5EXQ	Human cytochrome c Y48H	X-RAY DIFFRACTION	1.6
3ZCF	Structure of recombinant human cytochrome c	X-RAY DIFFRACTION	1.65
6DUJ	Crystal structure of A51V variant of Human Cytochrome c	X-RAY DIFFRACTION	1.82
3NWV	Human cytochrome c G41S	X-RAY DIFFRACTION	1.9
6XNK	Crystal structure of dimeric K72A human cytochrome c alkaline conformer	X-RAY DIFFRACTION	2.08
6ECJ	Human cytochrome c G41T	X-RAY DIFFRACTION	2.7
1J3S	Solution Structure of Reduced Recombinant Human Cytochrome c	SOLUTION NMR
2N3Y	NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state	SOLUTION NMR
2N9I	Solution structure of reduced human cytochrome c	SOLUTION NMR
2N9J	Solution structure of oxidized human cytochrome c	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P99999-F1	97.95	0.98

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4)

Position	Role
15	heme c
18	heme c
19	heme c
81	heme c

Post-translational modifications (7)

Type	Positions
N6-succinyllysine	73, 56
Phosphotyrosine	98, 49
N6-acetyllysine	100, 73
N-acetylglycine	2

Mutagenesis-validated functional residues (6)

Position	Phenotype
6	no effect on covalent heme attachment.
11	decreased covalent heme attachment.
11	no effect on covalent heme attachment.
15	decreased covalent heme attachment.
18	decreased covalent heme attachment.
19	loss of covalent heme attachment.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 30; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

30 pathways:

ID	Pathway	Evidence
R-HSA-111459	Activation of caspases through apoptosome-mediated cleavage	curated
R-HSA-9707564	Cytoprotection by HMOX1	curated
R-HSA-3299685	Detoxification of Reactive Oxygen Species	curated
R-HSA-111458	Formation of apoptosome	curated
R-HSA-5620971	Pyroptosis	curated
R-HSA-111457	Release of apoptotic factors from the mitochondria	curated
R-HSA-611105	Respiratory electron transport	curated
R-HSA-5628897	TP53 Regulates Metabolic Genes	curated
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis	curated
R-HSA-1428517	Aerobic respiration and respiratory electron transport	—
R-HSA-109581	Apoptosis	—
R-HSA-111471	Apoptotic factor-mediated response	—
R-HSA-9711123	Cellular response to chemical stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-111461	Cytochrome c-mediated apoptotic response	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-109606	Intrinsic Pathway for Apoptosis	—
R-HSA-1430728	Metabolism	—
R-HSA-1592230	Mitochondrial biogenesis	—
R-HSA-1852241	Organelle biogenesis and maintenance	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5218859	Regulated Necrosis	—
R-HSA-9627069	Regulation of the apoptosome activity	electronic
R-HSA-111463	SMAC (DIABLO) binds to IAPs	electronic
R-HSA-111464	SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes	electronic
R-HSA-111469	SMAC, XIAP-regulated apoptotic response	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 319 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, MODULE_93, MORF_ESPL1, WWTAAGGC_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, BASSO_B_LYMPHOCYTE_NETWORK, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MORF_UBE2N, DITTMER_PTHLH_TARGETS_UP, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, KYNG_DNA_DAMAGE_DN, MORF_HDAC2, RODWELL_AGING_KIDNEY_NO_BLOOD_DN

GO Biological Process (8): mitochondrial electron transport, ubiquinol to cytochrome c (GO:0006122), mitochondrial electron transport, cytochrome c to oxygen (GO:0006123), cellular respiration (GO:0045333), apoptotic signaling pathway (GO:0097190), intrinsic apoptotic signaling pathway (GO:0097193), execution phase of apoptosis (GO:0097194), apoptotic process (GO:0006915), respiratory electron transport chain (GO:0022904)

GO Molecular Function (4): electron transfer activity (GO:0009055), heme binding (GO:0020037), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), cytosol (GO:0005829)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Apoptotic factor-mediated response	3
Cytochrome c-mediated apoptotic response	2
SMAC, XIAP-regulated apoptotic response	2
Cellular response to chemical stress	2
Mitochondrial biogenesis	1
Regulated Necrosis	1
Transcriptional Regulation by TP53	1
Aerobic respiration and respiratory electron transport	1
Formation of apoptosome	1
Programmed Cell Death	1
Apoptosis	1
Intrinsic Pathway for Apoptosis	1
Metabolism	1
Organelle biogenesis and maintenance	1

GO top-level categories

24 GO namespaces:

Category	Terms
aerobic electron transport chain	2
mitochondrial ATP synthesis coupled electron transport	2
apoptotic process	2
apoptotic signaling pathway	2
intracellular membrane-bounded organelle	2
cytoplasm	2
energy derivation by oxidation of organic compounds	1
signal transduction	1
intracellular signal transduction	1
cellular process	1
bleb assembly	1
programmed cell death	1
execution phase of apoptosis	1
electron transport chain	1
cellular respiration	1
molecular_function	1
tetrapyrrole binding	1
cation binding	1
binding	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
mitochondrial intermembrane space	CC	direct assay
mitochondrion	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

IntAct

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

showing 30 of 58 partners by confidence:

Partner	Interaction type	MIscore	Records
KRT40	physical association	0.720	6
APAF1	physical association	0.690	3
LRG1	association	0.620	2
APP	physical association	0.560	3
ASCL4	physical association	0.560	3
BRWD1	physical association	0.560	3
C3orf36	physical association	0.560	3
COA7	physical association	0.560	3
CROT	physical association	0.560	3
EIF3F	physical association	0.560	3
FAM9A	physical association	0.560	3
FOXD4L6	physical association	0.560	3
FYN	physical association	0.560	3
KCTD17	physical association	0.560	3
LONRF2	physical association	0.560	3
LRRC56	physical association	0.560	3
MEOX2	physical association	0.560	3
MLST8	physical association	0.560	3
PHF23	physical association	0.560	3
PPP1R21	physical association	0.560	3
RUSC1-AS1	physical association	0.560	3
SEMA4G	physical association	0.560	3
SNCA	physical association	0.560	3
SNW1	physical association	0.560	3
SYMPK	physical association	0.560	3
ZBTB14	physical association	0.560	3
CYC1-2	direct interaction	0.560	2
E7	physical association	0.550	2
TRAF6	proximity	0.540	2
FAAP100	association	0.530	1

BioGRID (215 interactions; top human partners by supporting records): USP53 (Affinity Capture-MS; 6 records), COX4I2 (Reconstituted Complex; 4 records), APAF1 (Affinity Capture-Western; 2 records), BCL2L1 (Co-localization; 2 records), CDK2 (Affinity Capture-MS; 2 records), CKMT2 (Cross-Linking-MS (XL-MS); 2 records), CUL9 (Affinity Capture-Western; 2 records), GSTK1 (Co-fractionation; 2 records), HCCS (Affinity Capture-MS; 2 records), KRAS (Synthetic Lethality; 2 records), KRT40 (Two-hybrid; 2 records), LRG1 (Affinity Capture-MS; 2 records), MYC (Affinity Capture-MS; 2 records), PHB2 (Cross-Linking-MS (XL-MS); 2 records), TNRC18 (Cross-Linking-MS (XL-MS); 2 records)

SIGNOR signaling

showing 25 of 28 signaling interactions:

A	Effect	B	Mechanism
BAK1	up-regulates	CYCS	relocalization
CYCS	“up-regulates activity”	APAF1	binding
TP53	up-regulates	CYCS
PRKAA1	“up-regulates quantity by expression”	CYCS	“transcriptional regulation”
BAK1	up-regulates	CYCS
BAX	up-regulates	CYCS
PINK1	“down-regulates quantity”	CYCS
“Caspase 8 complex”	“up-regulates activity”	CYCS
3a	“up-regulates activity”	CYCS
GHITM	“down-regulates quantity”	CYCS	relocalization
“CoQ-cytochrome c reductase-Mitochondrial respiratory chain complex III”	“up-regulates activity”	CYCS	“chemical modification”
CYCS	“up-regulates activity”	“Cytochrome c oxidase-Mitochondrial respiratory chain complex IV”
HCCS	“up-regulates activity”	CYCS	“chemical modification”
“heme b”	“up-regulates activity”	CYCS	“chemical modification”
CYCS	“up-regulates activity”	CASP9	binding
BID	“up-regulates activity”	CYCS
CASP8	“up-regulates activity”	CYCS
BAX	up-regulates	CYCS	relocalization
BCL2	“down-regulates activity”	CYCS
PPARGC1A	“up-regulates quantity by expression”	CYCS	“transcriptional regulation”
CYCS	up-regulates	Oxidative_phosphorylation
CYCS	“form complex”	Apoptosome	binding
AKT3	“down-regulates activity”	CYCS	phosphorylation
AKT2	“down-regulates activity”	CYCS	phosphorylation
AKT1	“down-regulates activity”	CYCS	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Apoptosome, 700 kDa	3	APAF1, CASP9, CYCS
Apoptosome	2	APAF1, CYCS

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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.

GO biological processes:

GO term	Partners	Fold	FDR
neuron apoptotic process	5	17.5×	5e-03
negative regulation of apoptotic process	9	5.9×	5e-03

Disease & clinical

Genetic variants

Variant evidence for CYCS: 65 ClinVar records (6 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	27
Likely benign	19
Benign	0

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
16917	NM_018947.6(CYCS):c.124G>A (p.Gly42Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
180656	NM_018947.6(CYCS):c.145T>C (p.Tyr49His)	Pathogenic	criteria provided, single submitter	2
1703823	NM_018947.6(CYCS):c.290C>A (p.Ala97Asp)	Likely pathogenic	criteria provided, single submitter	1
4895503	NM_018947.6(CYCS):c.193C>G (p.Leu65Val)	Likely pathogenic	criteria provided, single submitter	1
599385	NM_018947.6(CYCS):c.301_303del (p.Lys101del)	Pathogenic	no assertion criteria provided	1
812966	NM_018947.6(CYCS):c.295C>G (p.Leu99Val)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CYCS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 279):

Position(s)	Effect	Δscore	Sites
7:25123708	donor_gain	1.0000
7:25123714	donor_gain	1.0000
7:25123742	donor_gain	1.0000
7:25123750–25123751	donor_gain	1.0000	2
7:25123850–25123851	acceptor_loss	1.0000	6
7:25123949–25123950	donor_loss	1.0000	2
7:25124128–25124129	acceptor_loss	1.0000	3
7:25123949–25123950	donor_loss	0.9900	2
7:25124128–25124129	acceptor_loss	0.9900	2
7:25125198–25125199	donor_loss	0.9900	5

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	3.37e-06
Lung Adenocarcinoma (TCGA)	unfavorable	4.15e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	4.36e-05
Thyroid Carcinoma (TCGA)	unfavorable	4.86e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000228
Glioblastoma Multiforme (validation)	unfavorable	0.000839

Disease associations

OMIM: gene MIM:123970 | disease phenotypes: MIM:612004

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
thrombocytopenia 4	Strong	Autosomal dominant	2
autosomal thrombocytopenia with normal platelets	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
thrombocytopenia 4	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 10 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Bleeding and platelet disorders	green
Cytopenia - NOT Fanconi anaemia	green
Hypotonic infant	green
Inherited bleeding disorders	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial disorders	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): thrombocytopenia (MONDO:0002049), thrombocytopenia 4 (MONDO:0012775), (MONDO:0015679)

Orphanet (1): Hereditary thrombocytopenia with normal platelets (Orphanet:268322)

HPO phenotypes

3 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001873	Thrombocytopenia
HP:0011876	Abnormal platelet volume

GWAS associations

3 associations:

Study	Trait	p-value
GCST001915_19	Alzheimer’s disease (cognitive decline)	2e-7
GCST004867_13	Systemic lupus erythematosus	2e-6
GCST007202_11	High density lipoprotein cholesterol levels	3e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C567438	Thrombocytopenia 4 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2189163 (SINGLE PROTEIN), CHEMBL3885517 (PROTEIN COMPLEX)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Mesotetra(4-Carboxyphenyl)Porphine	KD	950 nM
CHEMBL5653589	KD	1440 nM
CHEMBL385913	KD	1500 nM
CHEMBL1213293	KD	1700 nM
CHEMBL2203815	EC50	14000 nM
CHEMBL2203816	EC50	14400 nM
CHEMBL252122	EC50	16800 nM
CHEMBL438407	KD	17000 nM
CHEMBL2203814	EC50	17000 nM
CHEMBL2203812	EC50	23900 nM
CHEMBL2203813	EC50	29900 nM

ChEMBL bioactivities

5 potent at pChembl≥5 of 12 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.97	Kd	107.3	nM	CHEMBL5653589
6.97	ED50	107.3	nM	CHEMBL5653589
6.02	Kd	950	nM	CHEMBL353314
5.82	Kd	1500	nM	CHEMBL385913
5.77	Kd	1700	nM	CHEMBL1213293

PubChem BioAssay actives

4 with measured affinity, of 76 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148188: Binding affinity to human CYCS incubated for 45 mins by Kinobead based pull down assay	kd	0.1073	uM
4-[10,15,20-tris(4-carboxyphenyl)-21,24-dihydroporphyrin-5-yl]benzoic acid	495781: Binding affinity to Cytochrome C	kd	0.9500	uM
5-[4-[10,15,20-tris[4-(3,5-dicarboxyphenyl)phenyl]-21,24-dihydroporphyrin-5-yl]phenyl]benzene-1,3-dicarboxylic acid	495781: Binding affinity to Cytochrome C	kd	1.5000	uM
(3S)-3-[[3-[[(2S)-3-carboxy-1-methoxy-1-oxopropan-2-yl]carbamoyl]-5-[4-[10,15,20-tris[4-[3,5-bis[[(2S)-3-carboxy-1-methoxy-1-oxopropan-2-yl]carbamoyl]phenyl]phenyl]-21,23-dihydroporphyrin-5-yl]phenyl]benzoyl]amino]-4-methoxy-4-oxobutanoic acid	495781: Binding affinity to Cytochrome C	kd	1.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects localization, decreases reaction, affects reaction, increases expression, increases reaction (+1 more)	15
Doxorubicin	affects response to substance, affects expression, affects localization, affects cotreatment, increases expression (+2 more)	12
Acetylcysteine	decreases reaction, increases expression, decreases expression, affects localization	8
Quercetin	affects expression, affects localization, increases expression, decreases reaction, increases reaction (+1 more)	8
Paclitaxel	affects cotreatment, affects localization, increases expression, increases secretion	8
sodium arsenite	decreases reaction, increases expression, affects localization, decreases expression, affects cotreatment (+2 more)	7
Cisplatin	affects cotreatment, increases expression, affects expression, affects localization, decreases expression	7
Plant Extracts	affects localization, decreases reaction, decreases expression, increases abundance, increases expression	7
Cadmium	affects cotreatment, increases expression, affects localization, decreases expression, decreases reaction (+2 more)	6
Copper	affects localization, decreases expression, increases activity, increases metabolic processing, increases reaction (+2 more)	6
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, affects cotreatment, increases expression (+2 more)	6
bisphenol A	increases methylation, decreases reaction, affects expression, decreases expression, increases expression	5
Arsenic Trioxide	affects localization, increases secretion, increases reaction, affects cotreatment, increases expression	5
Estradiol	increases expression, affects localization, decreases reaction, affects reaction	5
Cannabidiol	affects cotreatment, increases expression, decreases reaction, decreases expression	4
Tamoxifen	decreases reaction, affects cotreatment, affects expression, increases expression, affects localization	4
cypermethrin	increases expression, increases secretion, affects reaction, decreases reaction, affects localization	3
hydroquinone	increases expression, affects localization, decreases reaction	3
alvocidib	affects localization, affects cotreatment, decreases reaction	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, affects localization	3
pterostilbene	affects localization, increases expression	3
pyrazolanthrone	decreases reaction, increases expression, affects localization, increases reaction	3
Troglitazone	affects binding, affects localization, decreases activity, decreases reaction, decreases expression (+1 more)	3
Curcumin	affects cotreatment, increases expression, affects localization, affects binding	3
Drugs, Chinese Herbal	affects localization, increases expression	3
Glucose	decreases reaction, increases expression, affects cotreatment	3
Nitric Oxide	affects localization, decreases secretion	3
Oxygen	decreases reaction, increases expression, increases reaction, affects expression, affects reaction (+1 more)	3
Paraquat	affects cotreatment, decreases reaction, increases expression, affects localization	3

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1218067	Binding	Binding affinity to Cytochrome C	A novel class of meso-tetrakis-porphyrin derivatives exhibits potent activities against hepatitis C virus genotype 1b replicons in vitro. — *Antimicrob Agents Chemother*

Clinical trials (associated diseases)

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

1 trials:

NCT	Phase	Status	Title
NCT07026578	Not specified	ACTIVE_NOT_RECRUITING	Unravelling the Role of Apoptosis in Platelets Biogenesis Through the Study of the Thrombocytopenia THC4

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CYCS across ~30M SureChEMBL compounds — explore on Sugi Predict.