CKB

Summary

CKB (creatine kinase B, HGNC:1991) is a protein-coding gene on chromosome 14q32.33, encoding Creatine kinase B-type (P12277). Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate).

The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in brain as well as in other tissues, and as a heterodimer with a similar muscle isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family. A pseudogene of this gene has been characterized.

Source: NCBI Gene 1152 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 42 total
• GTEx eGene: eQTL in 25 tissues, sQTL in 9 (q < 0.05)
• Constraint (gnomAD): pLI 0.12 (intermediate), LOEUF 0.72 (unconstrained)
• MANE Select transcript: NM_001823
• Interaction hub: 2,878 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1991
Approved symbol	CKB
Name	creatine kinase B
Location	14q32.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166165
Ensembl biotype	protein_coding
OMIM	123280
Entrez	1152

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 15 protein_coding, 10 retained_intron, 8 nonsense_mediated_decay

MANE Select: ENST00000348956

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 10, TSL 3: 1, TSL 4: 2, TSL 5: 3

ENST00000348956, ENST00000553528, ENST00000553610, ENST00000553652, ENST00000553878, ENST00000553994, ENST00000554282, ENST00000554426, ENST00000554705, ENST00000554989, ENST00000555039, ENST00000555366, ENST00000555659, ENST00000555770, ENST00000557287, ENST00000557530, ENST00000557569, ENST00000689346, ENST00000873263, ENST00000873264, ENST00000955391, ENST00000955392, ENST00000955393, ENST00001008556, ENST00001018638, ENST00001018640, ENST00001018643, ENST00001018644, ENST00001018646, ENST00001018649, ENST00001018650, ENST00001018652, ENST00001139527

RefSeq mRNA: 2 — MANE Select: NM_001823 NM_001362531, NM_001823

CCDS: CCDS91943, CCDS9981

Canonical transcript exons

ENST00000348956 — 8 exons

Exon	Start	End
ENSE00001100366	103519667	103520042
ENSE00002525462	103522766	103522830
ENSE00003498688	103522301	103522505
ENSE00003524543	103522023	103522177
ENSE00003554128	103520469	103520592
ENSE00003594505	103521818	103521950
ENSE00003648867	103520122	103520311
ENSE00003789149	103521263	103521434

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 434.2878 / max 6066.6402, expressed in 1743 samples.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, frontal lobe, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CKB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	9.1e-82	+0.78	14:103512871:CGTG:C
Skin Sun Exposed Lower leg	eqtl	1.6e-78	+0.72	14:103487197:G:A
Pancreas	eqtl	3.1e-30	+0.65	14:103520968:C:A
Cells Cultured fibroblasts	eqtl	1.0e-14	+0.22	14:103429503:C:T
Artery Aorta	eqtl	7.6e-11	+0.26	14:103539823:C:T
Testis	sqtl	1.7e-09	-0.57	14:103403512:G:C
Nerve Tibial	eqtl	1.5e-08	-0.15	14:103541822:C:T
Esophagus Mucosa	eqtl	4.1e-08	-0.14	14:103533010:G:C
Thyroid	eqtl	3.2e-07	+0.19	14:103387023:A:C
Testis	eqtl	5.1e-07	+0.22	14:103478575:G:A
Skin Not Sun Exposed Suprapubic	sqtl	6.3e-07	-0.37	14:103512871:CGTG:C
Whole Blood	eqtl	6.4e-07	-0.18	14:103534465:AG:A
Skin Sun Exposed Lower leg	sqtl	7.6e-07	-0.35	14:103487197:G:A
Liver	eqtl	1.1e-06	-0.42	14:103545092:G:A
Ovary	eqtl	1.3e-06	+0.41	14:103545157:C:T
Pituitary	eqtl	3.2e-06	+0.30	14:103520968:C:A
Artery Tibial	eqtl	3.4e-06	-0.11	14:103523259:AC:A
Esophagus Mucosa	sqtl	1.1e-04	+0.39	14:103545157:C:T
Prostate	eqtl	1.2e-04	-0.23	14:103525759:C:G
Adrenal Gland	eqtl	1.8e-04	-0.28	14:103548353:T:C

FANTOM5 promoters

showing 10 of 19 alternative TSS:

Promoter ID	TPM avg	Samples expressed
145101	413.8002	1670
145091	4.2967	808
145098	3.0790	702
145090	2.5540	670
145083	1.8954	565
145100	1.4897	512
145085	1.1711	594
145099	1.0986	433
145097	0.9565	421
145088	0.8824	361

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.94	gold quality
cerebellar hemisphere	UBERON:0002245	99.93	gold quality
cerebellar cortex	UBERON:0002129	99.92	gold quality
right frontal lobe	UBERON:0002810	99.92	gold quality
ventricular zone	UBERON:0003053	99.92	gold quality
prefrontal cortex	UBERON:0000451	99.87	gold quality
caudate nucleus	UBERON:0001873	99.86	gold quality
cerebellum	UBERON:0002037	99.86	gold quality
nucleus accumbens	UBERON:0001882	99.84	gold quality
amygdala	UBERON:0001876	99.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.78	gold quality
cingulate cortex	UBERON:0003027	99.77	gold quality
anterior cingulate cortex	UBERON:0009835	99.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.75	gold quality
frontal cortex	UBERON:0001870	99.73	gold quality
ganglionic eminence	UBERON:0004023	99.72	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.72	gold quality
right uterine tube	UBERON:0001302	99.71	gold quality
putamen	UBERON:0001874	99.71	gold quality
lower esophagus	UBERON:0013473	99.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.70	gold quality
neocortex	UBERON:0001950	99.68	gold quality
paraflocculus	UBERON:0005351	99.67	gold quality
cortical plate	UBERON:0005343	99.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.65	gold quality
transverse colon	UBERON:0001157	99.64	gold quality
body of stomach	UBERON:0001161	99.63	gold quality
middle frontal gyrus	UBERON:0002702	99.62	gold quality
mucosa of transverse colon	UBERON:0004991	99.59	gold quality
telencephalon	UBERON:0001893	99.58	gold quality
right testis	UBERON:0004534	99.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.58	gold quality
left testis	UBERON:0004533	99.57	gold quality
sigmoid colon	UBERON:0001159	99.56	gold quality
apex of heart	UBERON:0002098	99.55	gold quality
cerebral cortex	UBERON:0000956	99.54	gold quality
spinal cord	UBERON:0002240	99.46	gold quality
mucosa of stomach	UBERON:0001199	99.45	gold quality
postcentral gyrus	UBERON:0002581	99.45	gold quality
parietal lobe	UBERON:0001872	99.44	gold quality
left uterine tube	UBERON:0001303	99.43	gold quality
brain	UBERON:0000955	99.42	gold quality
central nervous system	UBERON:0001017	99.42	gold quality
forebrain	UBERON:0001890	99.42	gold quality
hypothalamus	UBERON:0001898	99.42	gold quality
frontal pole	UBERON:0002795	99.39	gold quality
Ammon’s horn	UBERON:0001954	99.38	gold quality
lateral globus pallidus	UBERON:0002476	99.38	gold quality
rectum	UBERON:0001052	99.34	gold quality
right atrium auricular region	UBERON:0006631	99.31	gold quality
temporal lobe	UBERON:0001871	99.29	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.29	gold quality
superior frontal gyrus	UBERON:0002661	99.27	gold quality
cerebellar vermis	UBERON:0004720	99.21	gold quality
popliteal artery	UBERON:0002250	99.19	gold quality
tibial artery	UBERON:0007610	99.19	gold quality
ventral tegmental area	UBERON:0002691	99.18	gold quality
colon	UBERON:0001155	99.15	gold quality
stomach	UBERON:0000945	99.14	gold quality
lower esophagus mucosa	UBERON:0035834	99.13	gold quality
body of uterus	UBERON:0009853	99.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.11	gold quality
cranial nerve II	UBERON:0000941	99.10	gold quality
right lobe of thyroid gland	UBERON:0001119	99.08	gold quality
fundus of stomach	UBERON:0001160	99.08	gold quality
right coronary artery	UBERON:0001625	99.08	gold quality
large intestine	UBERON:0000059	99.06	gold quality
left lobe of thyroid gland	UBERON:0001120	99.05	gold quality
superior vestibular nucleus	UBERON:0007227	99.05	gold quality
prostate gland	UBERON:0002367	99.04	gold quality
midbrain	UBERON:0001891	99.01	gold quality
substantia nigra	UBERON:0002038	99.00	gold quality
pons	UBERON:0000988	98.98	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.97	gold quality
endocervix	UBERON:0000458	98.96	gold quality
adenohypophysis	UBERON:0002196	98.95	gold quality
inferior vagus X ganglion	UBERON:0005363	98.91	gold quality
periodontal ligament	UBERON:0008266	98.90	gold quality
cardiac atrium	UBERON:0002081	98.85	gold quality
metanephros cortex	UBERON:0010533	98.82	gold quality
adult organism	UBERON:0007023	98.81	gold quality
ectocervix	UBERON:0012249	98.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.73	gold quality
heart left ventricle	UBERON:0002084	98.72	gold quality
occipital lobe	UBERON:0002021	98.70	gold quality
skin of leg	UBERON:0001511	98.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.66	gold quality
substantia nigra pars compacta	UBERON:0001965	98.64	gold quality
orbitofrontal cortex	UBERON:0004167	98.63	gold quality
cardia of stomach	UBERON:0001162	98.62	gold quality
colonic mucosa	UBERON:0000317	98.60	gold quality
right lung	UBERON:0002167	98.60	gold quality
thyroid gland	UBERON:0002046	98.59	gold quality
subthalamic nucleus	UBERON:0001906	98.57	gold quality
cardiac ventricle	UBERON:0002082	98.57	gold quality
corpus callosum	UBERON:0002336	98.55	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.55	gold quality
testis	UBERON:0000473	98.53	gold quality
seminal vesicle	UBERON:0000998	98.53	gold quality

Single-cell (SCXA)

Detected in 38 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	5141.96
E-MTAB-7008	yes	3422.69
E-HCAD-5	yes	3161.78
E-MTAB-8410	yes	2915.44
E-GEOD-75140	yes	2890.89
E-MTAB-9388	yes	2868.21
E-MTAB-7407	yes	2305.35
E-MTAB-6701	yes	1832.78
E-CURD-11	yes	1275.99
E-CURD-6	yes	268.19
E-GEOD-125970	yes	47.40
E-MTAB-10287	yes	43.85
E-CURD-119	yes	43.17
E-HCAD-35	yes	42.83
E-CURD-112	yes	31.97

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	1664.7
Postcentral gyrus	tissue	1389.5
Putamen	tissue	1299.1
Frontal cortex	tissue	1264.2
Nucleus accumbens	tissue	1187.7
Basal ganglia	tissue	1154.7	medium
Spinal cord	tissue	1007.4
Superior colliculi	tissue	936.3
Cerebral cortex	tissue	930.8	high
Somatosensory cortex	tissue	930.8
Hippocampus	tissue	930.6	medium
Medulla oblongata	tissue	890.9
Midbrain	tissue	843.4
Thalamus	tissue	841.8
Pons	tissue	819.2
Occipital cortex	tissue	789.1
Ventral forebrain	tissue	746.4
Substantia nigra	tissue	715.7
Motor cortex	tissue	679.3
Locus coeruleus	tissue	669.9
Temporal cortex	tissue	612.1
Periaqueductal gray	tissue	591.0
Hippocampal formation	tissue	567.1
Entorhinal cortex	tissue	565.1
Prefrontal cortex	tissue	557.6
Retrosplenial and cingulate cortex	tissue	556.1
Olfactory bulb	tissue	531.3
Cerebellum	tissue	521.2	high
Retrosplenial cortex	tissue	521.2
Hypothalamus	tissue	506.4
Choroid plexus	tissue	488.2
Septum	tissue	487.5
Insular cortex	tissue	472.2
Retina	tissue	438.2
Amygdala	tissue	419.1
Colon	tissue	311.2	not detected
Corpus callosum	tissue	303.9
Prostate	tissue	251.3	medium
Seminal vesicle	tissue	196.7	not detected
Stomach 1	tissue	186.6	medium
Vagina	tissue	151.2	not detected
Rectum	tissue	142.8	medium
Pituitary gland	tissue	108.1
Smooth muscle	tissue	106.2	not detected
Parathyroid gland	tissue	101.5	not detected
Heart muscle	tissue	92.4	low
Adipose tissue	tissue	85.1	low
Fallopian tube	tissue	84.1	not detected
Endometrium 1	tissue	71.4	not detected
Skeletal muscle	tissue	64.3	low
Cervix	tissue	58.3	not detected
Adrenal gland	tissue	56.7	not detected
Kidney	tissue	54.8	medium
Esophagus	tissue	51.2	not detected
Testis	tissue	48.3	not detected
Urinary bladder	tissue	44.2	not detected
Tongue	tissue	44.0
Skin 1	tissue	38.9	not detected
Small intestine	tissue	36.5	not detected
Salivary gland	tissue	35.8	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Cerebellar nuclei (1437.3), Caudate nucleus (1392.7), Posterior thalamic nucleus (1359.3), Lateral geniculate body (1335.1), Pulvinar (1229.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, PARP1, TFAP2A, TP53

Functional genomics

gnomAD constraint: pLI 0.117, LOEUF 0.724, missense Z 0.925 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000348956 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:103,519,867–103,522,103	314 / 409.4	0.77	no
14:103,522,104–103,522,341	25 / 54.9	0.46	no
14:103,522,342–103,522,493	74 / 70.6	1.05	no

Literature-anchored findings (GeneRIF, showing 40)

• 2D fingerprinting & mass spectrometry reveal specific targets of protein oxidation in Alzheimer’s disease brain, including creatine kinase BB, suggesting involvement of oxidatively modified proteins in neurodegeneration. (PMID:12160938)
• Expression of CKB mRNA and CK-B sometimes occurred in blastic transformation of the hematopoietic system (PMID:15996648)
• CKB was expressed in 78% of colon tumors (PMID:16424007)
• GM130 and BB-CK co-localize specifically in a transient fashion during early prophase of mitosis, when GM130 plays an important role in Golgi fragmentation that starts also at early prophase. (PMID:17036164)
• The asymmetric unit contained two molecules of CKB, giving a crystal volume per protein mass (Vm) of 1.80 A3 Da-1 and a solvent content of 31.6%. (PMID:18309274)
• Autoantibodies to EsteD and BB-CK produced in experimental autoimmune uveoretinitis -induced mice were also detected in some endogenous uveitis patients, suggesting that these proteins might be autoantigens. (PMID:18552983)
• Using a yeast 2-hybrid it was discovered that the C-terminal domain of KCC3, that is lost in most hereditary motor and sensory neuropathy with agenesis of the corpus callosum-causing mutations, directly interacts with brain-specific creatine kinase. (PMID:18566107)
• The Tat-CK fusion protein markedly increased endogenous CK activity levels within PC12 cells. (PMID:18682038)
• Data show that dose-response inactivation by 4HNE (4-hydroxynonenal) of hBAT (human bile acid CoA:amino acid N-acyltransferase) and CKBB (cytosolic brain isoform of creatine kinase) is associated with site-specific modifications. (PMID:18793185)
• Three structural aspects of human-brain-type-creatine-kinase were identified by X-ray crystallography: the ligand-free-form at 2.2A; the ADP-Mg2+, nitrate, and creatine complex (transition-state-analogue complex; TSAC); and the ADP-Mg2+-complex at 2.0A. (PMID:18977227)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Report the effects of prior calcium channel blocker therapy on creatine kinase-MB (myocardial form) levels after percutaneous coronary interventions. (PMID:19337554)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• The correlation of CK-BB as a disease biomarker in both CNS and peripheral tissues from Huntington’s disease mice and patients may provide a powerful means to assess disease progression and prognosis. (PMID:20460152)
• Phosphocreatine metabolism in the normal appearing white matter in multiple sclerosis is impaired due to decreased CK-B levels. (PMID:20520825)
• A single troponin I value at 3 days from symptom onset is a better predictor of infarct size compared to peak values and CK-MB. (PMID:20588136)
• CKB was up-regulated in women older than 38 years, and its expression in cumulus cells was associated with embryo quality (PMID:20721618)
• These observations suggested that the ability to generate the oxidized form could protect BBCK against the intracellular oxidative stress. (PMID:20923681)
• Data demonstrate that the downregulation of CKB may play an important role in colon cancer progression by promoting EMT. (PMID:21308735)
• The results suggested that the intra- and inter-subunit domain interactions modified the behavior of kinetic refolding. (PMID:21931810)
• Cigarette smoke induced carbonylation and subsequent degradation of creatine kinase B are involved in the regulation of senescence in bronchial epithelial cells. (PMID:21980054)
• de-methylated CKB gene is inherited that leads to high CKB expression levels in myeloic precursor cells in the bone marrow (PMID:22088263)
• His103 and Phe107 in hASB9-2 are essential for binding to CKB. (PMID:22418839)
• study found promoter SNPs of CKB and TPI1 were weakly associated with schizophrenia;in addition, IFNG polymorphisms were associated with schizophrenia; results suggest that IFNG and proteins affected by IFNG may play a role in the pathogenesis of schizophrenia (PMID:22623148)
• effects of osmolytes on human brain-type creatine kinase folding (PMID:22885020)
• analysis of SNPs and their effect on creatine kinase structure and function (PMID:23049898)
• Estimation of CK and its CK isoenzyme fractions can aid in quick and accurate diagnosis of tubal ectopic pregnancy. (PMID:23876027)
• We found that most patients with macular telangiectasia-2 possess retinal autoantibodies, the most prevalent of which were directed against AGL, RBP3, and CK-B. (PMID:23882694)
• increased serum Ckbb reflects failure of osteoclasts or suppression of osteoclasts in children with osteogenesis imperfecta during neridronate treatment (PMID:24518563)
• CK-MB levels were higher after ERCP in non-ischemic patients compared with a myocardial ischemia group. Creatine phosphokinase levels did not differ significantly between groups. (PMID:25141318)
• CK-B catalytic activity also helps in the formation of protrusive ruffle structures which are actin-dependent and abundant on the surface of both unstimulated and LPS-activated macrophages. (PMID:25538032)
• SRC, LYN and CKB expression or DNA methylation could be useful markers for predicting tumor progression. (PMID:26460485)
• membrane localization of BCK seems to be an important and regulated feature for the fueling of membrane-located, ATP-dependent processes, stressing again the importance of local rather than global ATP concentrations. (PMID:27318991)
• The data revealed a varying but significant increase of CK activity in CKBE individuals as compared to controls, reaching an almost 800-fold increase in two CKBE individuals which also had increased erythrocyte creatine. (PMID:28364583)
• These findings support increased CK activity as protection against ischaemia-reperfusion injury, in particular, protection via CKMT2 in a cardiac-relevant cell line, which merits further investigation in vivo. (PMID:28806770)
• Association and oligomerization of Prx II could take part in recovery and protection of the CK BB enzyme activity from inactivation during heat-induced stress. (PMID:29227081)
• Clinical impact of creatine phosphokinase and c-reactive protein as predictors of postgastrectomy complications in patients with gastric cancer. (PMID:33485312)
• Creatine kinase B controls futile creatine cycling in thermogenic fat. (PMID:33597756)
• CKB inhibits epithelial-mesenchymal transition and prostate cancer progression by sequestering and inhibiting AKT activation. (PMID:34706306)
• Creatine kinase B suppresses ferroptosis by phosphorylating GPX4 through a moonlighting function. (PMID:37156912)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	ckbb	ENSDARG00000043257
danio_rerio	ckba	ENSDARG00000069752
mus_musculus	Ckb	ENSMUSG00000001270
rattus_norvegicus	Ckb	ENSRNOG00000010872
drosophila_melanogaster	Argk1	FBGN0000116
drosophila_melanogaster	Argk2	FBGN0035957
drosophila_melanogaster	CG4546	FBGN0038373
drosophila_melanogaster	CG30274	FBGN0050274
caenorhabditis_elegans		WBGENE00009706
caenorhabditis_elegans	ZC434.8	WBGENE00013894
caenorhabditis_elegans	F32B5.1	WBGENE00017975
caenorhabditis_elegans		WBGENE00018519
caenorhabditis_elegans	W10C8.5	WBGENE00021128

Paralogs (4): CKM (ENSG00000104879), CKMT2 (ENSG00000131730), CKMT1A (ENSG00000223572), CKMT1B (ENSG00000237289)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88407) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 17 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased exploration in new environment	1
decreased exploration in new environment	1
abnormal spatial learning	1
abnormal vibrissa morphology	1
decreased brain weight	1
increased mean corpuscular volume	1
abnormal hippocampal mossy fiber morphology	1
decreased susceptibility to pharmacologically induced seizures	1
increased lean body mass	1
abnormal auditory brainstem response	1
increased lymphocyte cell number	1
increased mean corpuscular hemoglobin	1
decreased mean platelet volume	1
decreased prepulse inhibition	1
decreased total body fat amount	1
increased red blood cell distribution width	1
increased bone mineral content	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
Clostridium kluyveri DSM 555	A5N4L9	100.0%	Diamond
Clostridium kluyveri NBRC 12016	B9DY81	100.0%	Diamond
Pongo abelii	Q5R7B5	99.8%	Diamond
Penaeus vannamei	B0FRF9	99.7%	Diamond
Metapenaeus ensis	B1PVZ9	99.7%	Diamond
Listeria monocytogenes serotype 4b str. CLIP 80459	C1KYG4	99.7%	Diamond
Scylla serrata	C9EIP1	99.7%	Diamond
Scylla paramamosain	H6VGI3	99.7%	Diamond
Listeria monocytogenes serotype 4b str. F2365	Q724I1	99.7%	Diamond
Canis lupus familiaris	P05124	99.5%	Diamond
Sus scrofa	Q29594	99.5%	Diamond
Callinectes bellicosus	A0A976YI25	99.2%	Diamond
Callinectes sapidus	Q9NH49	99.2%	Diamond
Bos taurus	Q5EA61	99.0%	Diamond
Listeria monocytogenes EGD-e	Q48759	98.5%	Diamond
Oryctolagus cuniculus	P00563	97.9%	Diamond
Torpedo marmorata	P00566	97.9%	Diamond
Tetronarce californica	P04414	97.9%	Diamond
Penaeus monodon	C7E3T4	97.5%	Diamond
Carcinus maenas	Q9U9J4	97.5%	Diamond
Listeria innocua Clip11262	Q92F44	97.4%	Diamond
Eriocheir sinensis	Q9NH48	96.9%	Diamond
Pachygrapsus marmoratus	Q9GYX1	96.1%	Diamond
Listeria monocytogenes HCC23	B8DGJ3	95.6%	Diamond
Penaeus japonicus	P51545	95.5%	Diamond
Procambarus clarkii	H6VGI2	95.2%	Diamond
Homarus gammarus	P14208	95.2%	Diamond
Oncorhynchus mykiss	P24722	91.7%	Diamond
Squalus acanthias	P26460	91.7%	Diamond
Gallus gallus	P00565	91.3%	Diamond
Schistocerca americana	P91798	86.2%	Diamond
Plodia interpunctella	Q95PM9	86.2%	Diamond
Apis mellifera	O61367	86.0%	Diamond
Artemia franciscana	Q95V58	84.1%	Diamond
Polybetes pythagoricus	A0A286R7K5	81.2%	Diamond
Limulus polyphemus	P51541	81.2%	Diamond
Turbo cornutus	O15989	79.4%	Diamond
Haliotis madaka	P51544	79.4%	Diamond
Trypanosoma cruzi	O96507	76.2%	Diamond
Amphioctopus fangsiao	G1ESZ9	71.1%	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
TRMT61A	protein-coding	115708
COA8	protein-coding	84334
BAG5	protein-coding	9529
MARK3	protein-coding	4140

Protein

Protein identifiers

Creatine kinase B-type — P12277 (reviewed: P12277)

Alternative names: Brain creatine kinase, Creatine kinase B chain, Creatine phosphokinase B-type

All UniProt accessions (9): A0A0S2Z471, P12277, G3V2I1, G3V461, G3V4N7, H0YJG0, H0YJJ7, H0YJK0, V9HWH2

UniProt curated annotations — full annotation on UniProt →

Function. Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation. During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work.

Subunit / interactions. Dimer of identical or non-identical chains, which can be either B (brain type) or M (muscle type). With MM being the major form in skeletal muscle and myocardium, MB existing in myocardium, and BB existing in many tissues, especially brain. Interacts with SLC12A6 (via C-terminus); the interaction may be required for SLC12A6 potassium-chloride cotransport activity.

Subcellular location. Cytoplasm. Cytosol. Mitochondrion. Cell membrane.

Post-translational modifications. Ubiquitinated by the ECS(ASB9) complex, leading to its degradation by the proteasome.

Domain organisation. The internal MTS-like signal (iMTS-L) mediates targeting to mitochondria thermogenic fat cells.

Similarity. Belongs to the ATP:guanido phosphotransferase family.

RefSeq proteins (2): NP_001349460, NP_001814* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000749	ATP-guanido_PTrfase	Family
IPR014746	Gln_synth/guanido_kin_cat_dom	Homologous_superfamily
IPR022413	ATP-guanido_PTrfase_N	Domain
IPR022414	ATP-guanido_PTrfase_cat	Domain
IPR022415	ATP-guanido_PTrfase_AS	Active_site
IPR036802	ATP-guanido_PTrfase_N_sf	Homologous_superfamily

Pfam: PF00217, PF02807

Enzyme classification (BRENDA)

• EC 2.7.3.2 — creatine kinase (BRENDA: 45 organisms, 67 substrates, 117 inhibitors, 317 Km, 122 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.042–20	133
CREATINE	0.35–167	102
PHOSPHOCREATINE	0.51–8.97	23
ADP	0.015–1.2	22
CREATINE PHOSPHATE	0.23–50	11
ALPHA-(RP)-BORANO SUBSTITUTED ADP	1	1
ALPHA-(SP)-BORANO SUBSTITUTED ADP	0.008	1
GLYCOCYAMINE	6.7	1
CYCLOCREATINE	—	0
N-ETHYLGLYCOCYAMINE	—	0

Catalyzed reactions (Rhea)

• creatine + ATP = N-phosphocreatine + ADP + H(+) (RHEA:17157)

UniProt features (81 total): helix 20, binding site 12, sequence conflict 11, strand 8, modified residue 7, turn 5, cross-link 4, mutagenesis site 4, sequence variant 3, domain 2, region of interest 2, initiator methionine 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
7BF1	Ca2+-Calmodulin in complex with peptide from brain-type creatine kinase in extended 1:2 …	X-RAY DIFFRACTION	1.24
3B6R	Crystal structure of Human Brain-type Creatine Kinase	X-RAY DIFFRACTION	2
3DRB	Crystal structure of Human Brain-type Creatine Kinase	X-RAY DIFFRACTION	2
3DRE	Crystal structure of Human Brain-type Creatine Kinase	X-RAY DIFFRACTION	2.2
7TUN	Crystal structure analysis of human CKB complex with a covalent compound	X-RAY DIFFRACTION	2.93
6V9H	Ankyrin repeat and SOCS-box protein 9 (ASB9), ElonginB (ELOB), and ElonginC (ELOC) bound …	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12277-F1	95.59	0.89

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

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 (12)

Position	Role
132	ATP
191	ATP
232	creatine
236	ATP
285	creatine
292	ATP
320–325	ATP
320	ATP
335	ATP
72	creatine
128–132	ATP
130	ATP

Post-translational modifications (11)

Type	Positions
Phosphoserine	4, 199, 309
Phosphothreonine	35, 322
Phosphotyrosine	125
3’-nitrotyrosine	269
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	45, 101, 107, 381

Mutagenesis-validated functional residues (4)

Position	Phenotype
283	complete loss of activity.
292	complete loss of activity.
292	42% of wild-type activity.
340	no change in activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-71288	Creatine metabolism	curated
R-HSA-9696264	RND3 GTPase cycle	curated
R-HSA-1430728	Metabolism	—
R-HSA-71291	Metabolism of amino acids and derivatives	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (3): substantia nigra development (GO:0021762), phosphocreatine biosynthetic process (GO:0046314), futile creatine cycle (GO:0140651)

GO Molecular Function (9): creatine kinase activity (GO:0004111), ATP binding (GO:0005524), ubiquitin protein ligase binding (GO:0031625), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), transferase activity, transferring phosphorus-containing groups (GO:0016772)

GO Cellular Component (4): mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Metabolism of amino acids and derivatives	1
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Metabolism	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

27 GO namespaces:

Category	Terms
cytoplasm	2
midbrain development	1
neural nucleus development	1
phosphocreatine metabolic process	1
phosphagen biosynthetic process	1
creatine kinase activity	1
metabolic process	1
phosphoamidase activity	1
adaptive thermogenesis	1
kinase activity	1
phosphotransferase activity, nitrogenous group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
ubiquitin-like protein ligase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
transferase activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
membrane	1
cell periphery	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
phosphocreatine biosynthetic process	BP	direct assay
substantia nigra development	BP	high-throughput mutant
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
creatine kinase activity	MF	direct assay
ubiquitin protein ligase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,878 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CKB	MB	P02144	945
CKB	DMD	P11532	924
CKB	DAG1	Q14118	890
CKB	GPT	P24298	883
CKB	CRP	P02741	882
CKB	DYSF	O75923	877
CKB	TNNI3	P19429	854
CKB	MYH14	Q7Z406	840
CKB	LAMA2	P24043	811
CKB	FKRP	Q9H9S5	797
CKB	ALB	P02768	784
CKB	FKTN	O75072	774
CKB	SGCA	Q16586	770
CKB	GPT2	Q8TD30	768
CKB	CAPN3	P20807	752

IntAct

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

22 partners by confidence:

Partner	Interaction type	MIscore	Records
ASB9	physical association	0.940	9
CKM	physical association	0.690	3
CUL3	physical association	0.620	1
SLC12A6	physical association	0.530	3
TCF4	physical association	0.500	1
DNM1L	colocalization	0.430	1
ECE1	physical association	0.370	3
ACD	physical association	0.370	1
ERBB2	physical association	0.370	1
ILK	physical association	0.370	1
MLH1	physical association	0.370	1
POT1	physical association	0.370	1
PPP1CA	physical association	0.370	1
SERP2	physical association	0.370	1
TAB1	physical association	0.370	1
TERF1	physical association	0.370	1
TINF2	physical association	0.370	1
DOCK7	association	0.350	1
TLE1	association	0.350	1
B9D2	proximity	0.270	1
DISC1	physical association	0.000	1
NFKB2	physical association	0.000	1

BioGRID (383 interactions; top human partners by supporting records): ASB9 (Two-hybrid; 19 records), CKM (Affinity Capture-MS; 6 records), CKMT1A (Cross-Linking-MS (XL-MS); 5 records), PARK2 (Affinity Capture-MS; 3 records), ALDOA (Co-fractionation; 2 records), ARHGAP24 (Affinity Capture-MS; 2 records), ARIH2 (Biochemical Activity; 2 records), CCNF (Proximity Label-MS; 2 records), CUL3 (Affinity Capture-MS; 2 records), DLD (Affinity Capture-MS; 2 records), ENO1 (Affinity Capture-MS; 2 records), GOLGA2 (Two-hybrid; 2 records), HSPE1 (Co-fractionation; 2 records), HUWE1 (Affinity Capture-MS; 2 records), KMT2A (Cross-Linking-MS (XL-MS); 2 records)

SIGNOR signaling

showing 4 of 5 signaling interactions:

A	Effect	B	Mechanism
creatine	“up-regulates activity”	CKB	“chemical activation”
CKB	“up-regulates quantity”	N-phosphocreatine	“chemical modification”
CKB	“up-regulates quantity”	ACTB	relocalization
ASB9	“down-regulates quantity by destabilization”	CKB	polyubiquitination

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
★ Emerin complex 52	23	DDX39A, ILF3, LEMD3, RBL2, H1-1, HNRNPK, HNRNPU, IQGAP1, NMI, PDCD4, SNRPD1, THRA, API5, CKB, EMD, HDGF, LSM8, YWHAQ, ACTB, C1QBP, HNRNPL, LMNB1, YWHAE

Disease & clinical

Genetic variants

Variant evidence for CKB: 42 ClinVar records (0 pathogenic / likely pathogenic); 10 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 537):

Position(s)	Effect	Δscore	Sites
14:103520043–103520044	acceptor_loss	1.0000	2
14:103520120–103520121	donor_loss	1.0000	5
14:103520312–103520313	acceptor_loss	1.0000	4
14:103520320	acceptor_gain	1.0000
14:103520425	donor_gain	1.0000
14:103520460	donor_gain	1.0000
14:103521261–103521262	donor_loss	1.0000	4
14:103521951	acceptor_gain	1.0000
14:103521951–103521952	acceptor_loss	1.0000	4
14:103522021–103522022	donor_loss	1.0000	3

AlphaMissense

1,465 missense substitutions predicted likely pathogenic (of 2,520 scored), across 295 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
M207	9	0.954	0.992
M240	9	0.935	0.994
M272	9	0.872	0.965
D233	8	0.999	1.000
D335	8	0.998	0.999
H97	8	0.996	0.999
F194	8	0.995	1.000
N286	8	0.992	1.000
D326	8	0.990	0.997
D78	8	0.989	0.997
D210	8	0.989	0.997
H66	8	0.985	0.999
H191	8	0.985	0.998
H296	8	0.981	0.999
H234	8	0.978	0.998
D62	8	0.977	0.996
D195	8	0.977	0.992
D54	8	0.970	0.994
N338	8	0.970	1.000
D340	8	0.968	0.992

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	1.36e-06
Colon Adenocarcinoma (validation)	favorable	7.02e-05

Disease associations

OMIM: gene MIM:123280 | disease phenotypes:

GWAS associations

10 associations:

Study	Trait	p-value
GCST008839_226	Height	9e-17
GCST002539_33	Schizophrenia	1e-13
GCST004521_166	Autism spectrum disorder or schizophrenia	2e-12
GCST010988_112	Adult body size	1e-11
GCST010703_116	Brain morphology (MOSTest)	2e-9
GCST005951_19	Body mass index	4e-9
GCST004521_37	Autism spectrum disorder or schizophrenia	6e-9
GCST007044_22	Extremely high intelligence	4e-8
GCST008163_3	Height	2e-7
GCST005194_216	Coronary artery disease	2e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6049 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases activity, decreases reaction, affects cotreatment, increases expression, decreases expression	6
bisphenol A	decreases expression, increases expression, affects cotreatment, affects expression	5
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	5
Valproic Acid	increases expression, increases methylation, affects expression	5
Cyclosporine	decreases expression	4
trichostatin A	affects cotreatment, decreases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cadmium	increases expression	2
Doxorubicin	affects expression, decreases expression	2
Lipopolysaccharides	increases expression, affects expression, affects response to substance, decreases reaction	2
Mustard Gas	increases alkylation, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Quercetin	decreases expression, increases activity	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression, affects cotreatment	2
Thapsigargin	decreases expression	2
Genistein	decreases reaction, increases activity, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
TL8-506	affects cotreatment, increases expression	1
4-oxoretinoic acid	decreases expression	1
biochanin A	increases activity	1
bufotalin	increases expression	1
daidzein	increases activity, decreases reaction	1
triphenyl phosphate	increases expression	1
propionaldehyde	increases expression	1
lead acetate	decreases expression, affects cotreatment	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1054174	Binding	Activity of human creatine kinase isoform BB assessed as formation of RO2433 triphosphate at 200 uM	The mechanism of action of beta-D-2’-deoxy-2’-fluoro-2’-C-methylcytidine involves a second metabolic pathway leading to beta-D-2’-deoxy-2’-fluoro-2’-C-methyluridine 5’-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. — *Antimicrob Agents Chemother*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SJ12	HAP1 CKB (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 82 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	Phase 2/3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	Phase 2/3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	Phase 1/2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	Phase 1/2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	Phase 1/2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	Phase 1/2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	Phase 1/2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	Phase 1/2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	Phase 1/2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	Phase 1/2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	Phase 1/2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	Phase 1/2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	Phase 1/2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	Phase 1/2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	Phase 1/2	COMPLETED	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	Early Phase 1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	Early Phase 1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	Early Phase 1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00295087	Not specified	COMPLETED	X-Chromosome Inactivation Status and Premature Ovarian Failure
NCT00417157	Not specified	COMPLETED	Modified Natural Cycle Offers a Chance of Pregnancy in Patients With Poor Response and High Basal FSH
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT00780897	Not specified	UNKNOWN	Premature Ovarian Failure (Genetic and Physiopathologic Analysis)
NCT01187524	Not specified	TERMINATED	The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
NCT01411644	Not specified	UNKNOWN	Pheno- & Genotyping POF (WHO III)
NCT02086318	Not specified	UNKNOWN	A New Algorithm to Predict Ovarian Age
NCT02467231	Not specified	ACTIVE_NOT_RECRUITING	Ovarian Reserve After Cancer: Longitudinal Effects
NCT02696889	Not specified	COMPLETED	Rejuvenation of Premature Ovarian Failure With Stem Cells
NCT02779374	Not specified	TERMINATED	Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency
NCT03207412	Not specified	UNKNOWN	Human Amniotic Epithelial Cells Treatment for Ovarian Insufficiency
NCT03381300	Not specified	ACTIVE_NOT_RECRUITING	Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
NCT03412487	Not specified	UNKNOWN	Ovarian Histopathology and Laparoscopic Assessment of Premature Ovarian Failure
NCT03474120	Not specified	UNKNOWN	Prospective Genetic Study in Patients With Ovarian Insufficiency
NCT03480412	Not specified	UNKNOWN	Second Step Protocol in Poor Ovarian Responder (POR)
NCT03542708	Not specified	COMPLETED	Injections of Autologous PRP in Women With Primary Ovarian Insufficiency
NCT03692572	Not specified	COMPLETED	Influence of Early Menopause on Sympathetic Activation and Cardiovascular Function in Older Women
NCT03840824	Not specified	COMPLETED	Blood Spot Self-administered Test and Assay
NCT03861715	Not specified	UNKNOWN	Single Follicular Dexarelix for LH Suppression During Ovarian Stimulation in Oocyte Donors.
NCT03924648	Not specified	COMPLETED	Endocan Levels in Women With Premature Ovarian Insufficiency