# CKB

> Gene · canonical: https://sugi.bio/atlas/gene/CKB/
> Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00

## 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](https://www.ncbi.nlm.nih.gov/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](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-6911) | yes | 5141.96 |
| [E-MTAB-7008](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-7008) | yes | 3422.69 |
| [E-HCAD-5](https://www.ebi.ac.uk/gxa/sc/experiments/E-HCAD-5) | yes | 3161.78 |
| [E-MTAB-8410](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-8410) | yes | 2915.44 |
| [E-GEOD-75140](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-75140) | yes | 2890.89 |
| [E-MTAB-9388](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-9388) | yes | 2868.21 |
| [E-MTAB-7407](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-7407) | yes | 2305.35 |
| [E-MTAB-6701](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-6701) | yes | 1832.78 |
| [E-CURD-11](https://www.ebi.ac.uk/gxa/sc/experiments/E-CURD-11) | yes | 1275.99 |
| [E-CURD-6](https://www.ebi.ac.uk/gxa/sc/experiments/E-CURD-6) | yes | 268.19 |
| [E-GEOD-125970](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-125970) | yes | 47.40 |
| [E-MTAB-10287](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-10287) | yes | 43.85 |
| [E-CURD-119](https://www.ebi.ac.uk/gxa/sc/experiments/E-CURD-119) | yes | 43.17 |
| [E-HCAD-35](https://www.ebi.ac.uk/gxa/sc/experiments/E-HCAD-35) | yes | 42.83 |
| [E-CURD-112](https://www.ebi.ac.uk/gxa/sc/experiments/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](https://gnomad.broadinstitute.org/)

#### 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](https://gnomad.broadinstitute.org/)

| 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](https://www.informatics.jax.org/marker/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](https://www.uniprot.org/uniprotkb/A5N4L9/entry) | 100.0% | Diamond |
| Clostridium kluyveri NBRC 12016 | [B9DY81](https://www.uniprot.org/uniprotkb/B9DY81/entry) | 100.0% | Diamond |
| Pongo abelii | [Q5R7B5](https://www.uniprot.org/uniprotkb/Q5R7B5/entry) | 99.8% | Diamond |
| Penaeus vannamei | [B0FRF9](https://www.uniprot.org/uniprotkb/B0FRF9/entry) | 99.7% | Diamond |
| Metapenaeus ensis | [B1PVZ9](https://www.uniprot.org/uniprotkb/B1PVZ9/entry) | 99.7% | Diamond |
| Listeria monocytogenes serotype 4b str. CLIP 80459 | [C1KYG4](https://www.uniprot.org/uniprotkb/C1KYG4/entry) | 99.7% | Diamond |
| Scylla serrata | [C9EIP1](https://www.uniprot.org/uniprotkb/C9EIP1/entry) | 99.7% | Diamond |
| Scylla paramamosain | [H6VGI3](https://www.uniprot.org/uniprotkb/H6VGI3/entry) | 99.7% | Diamond |
| Listeria monocytogenes serotype 4b str. F2365 | [Q724I1](https://www.uniprot.org/uniprotkb/Q724I1/entry) | 99.7% | Diamond |
| Canis lupus familiaris | [P05124](https://www.uniprot.org/uniprotkb/P05124/entry) | 99.5% | Diamond |
| Sus scrofa | [Q29594](https://www.uniprot.org/uniprotkb/Q29594/entry) | 99.5% | Diamond |
| Callinectes bellicosus | [A0A976YI25](https://www.uniprot.org/uniprotkb/A0A976YI25/entry) | 99.2% | Diamond |
| Callinectes sapidus | [Q9NH49](https://www.uniprot.org/uniprotkb/Q9NH49/entry) | 99.2% | Diamond |
| Bos taurus | [Q5EA61](https://www.uniprot.org/uniprotkb/Q5EA61/entry) | 99.0% | Diamond |
| Listeria monocytogenes EGD-e | [Q48759](https://www.uniprot.org/uniprotkb/Q48759/entry) | 98.5% | Diamond |
| Oryctolagus cuniculus | [P00563](https://www.uniprot.org/uniprotkb/P00563/entry) | 97.9% | Diamond |
| Torpedo marmorata | [P00566](https://www.uniprot.org/uniprotkb/P00566/entry) | 97.9% | Diamond |
| Tetronarce californica | [P04414](https://www.uniprot.org/uniprotkb/P04414/entry) | 97.9% | Diamond |
| Penaeus monodon | [C7E3T4](https://www.uniprot.org/uniprotkb/C7E3T4/entry) | 97.5% | Diamond |
| Carcinus maenas | [Q9U9J4](https://www.uniprot.org/uniprotkb/Q9U9J4/entry) | 97.5% | Diamond |
| Listeria innocua Clip11262 | [Q92F44](https://www.uniprot.org/uniprotkb/Q92F44/entry) | 97.4% | Diamond |
| Eriocheir sinensis | [Q9NH48](https://www.uniprot.org/uniprotkb/Q9NH48/entry) | 96.9% | Diamond |
| Pachygrapsus marmoratus | [Q9GYX1](https://www.uniprot.org/uniprotkb/Q9GYX1/entry) | 96.1% | Diamond |
| Listeria monocytogenes HCC23 | [B8DGJ3](https://www.uniprot.org/uniprotkb/B8DGJ3/entry) | 95.6% | Diamond |
| Penaeus japonicus | [P51545](https://www.uniprot.org/uniprotkb/P51545/entry) | 95.5% | Diamond |
| Procambarus clarkii | [H6VGI2](https://www.uniprot.org/uniprotkb/H6VGI2/entry) | 95.2% | Diamond |
| Homarus gammarus | [P14208](https://www.uniprot.org/uniprotkb/P14208/entry) | 95.2% | Diamond |
| Oncorhynchus mykiss | [P24722](https://www.uniprot.org/uniprotkb/P24722/entry) | 91.7% | Diamond |
| Squalus acanthias | [P26460](https://www.uniprot.org/uniprotkb/P26460/entry) | 91.7% | Diamond |
| Gallus gallus | [P00565](https://www.uniprot.org/uniprotkb/P00565/entry) | 91.3% | Diamond |
| Schistocerca americana | [P91798](https://www.uniprot.org/uniprotkb/P91798/entry) | 86.2% | Diamond |
| Plodia interpunctella | [Q95PM9](https://www.uniprot.org/uniprotkb/Q95PM9/entry) | 86.2% | Diamond |
| Apis mellifera | [O61367](https://www.uniprot.org/uniprotkb/O61367/entry) | 86.0% | Diamond |
| Artemia franciscana | [Q95V58](https://www.uniprot.org/uniprotkb/Q95V58/entry) | 84.1% | Diamond |
| Polybetes pythagoricus | [A0A286R7K5](https://www.uniprot.org/uniprotkb/A0A286R7K5/entry) | 81.2% | Diamond |
| Limulus polyphemus | [P51541](https://www.uniprot.org/uniprotkb/P51541/entry) | 81.2% | Diamond |
| Turbo cornutus | [O15989](https://www.uniprot.org/uniprotkb/O15989/entry) | 79.4% | Diamond |
| Haliotis madaka | [P51544](https://www.uniprot.org/uniprotkb/P51544/entry) | 79.4% | Diamond |
| Trypanosoma cruzi | [O96507](https://www.uniprot.org/uniprotkb/O96507/entry) | 76.2% | Diamond |
| Amphioctopus fangsiao | [G1ESZ9](https://www.uniprot.org/uniprotkb/G1ESZ9/entry) | 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](/atlas/gene/TRMT61A/) | protein-coding | 115708 |
| [COA8](/atlas/gene/COA8/) | protein-coding | 84334 |
| [BAG5](/atlas/gene/BAG5/) | protein-coding | 9529 |
| [MARK3](/atlas/gene/MARK3/) | protein-coding | 4140 |

<a id="protein-P12277"></a>

## 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 →](https://www.uniprot.org/uniprotkb/P12277/entry)

**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](https://amigo.geneontology.org/amigo/term/GO:0046314) | BP | direct assay |
| [substantia nigra development](https://amigo.geneontology.org/amigo/term/GO:0021762) | BP | high-throughput mutant |
| [cytosol](https://amigo.geneontology.org/amigo/term/GO:0005829) | CC | direct assay |
| [extracellular exosome](https://amigo.geneontology.org/amigo/term/GO:0070062) | CC | high-throughput assay |
| [creatine kinase activity](https://amigo.geneontology.org/amigo/term/GO:0004111) | MF | direct assay |
| [ubiquitin protein ligase binding](https://amigo.geneontology.org/amigo/term/GO:0031625) | 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](#clinvar) (0 pathogenic / likely pathogenic); [10 GWAS associations](#gwas-assoc).

#### 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 |

## Related Atlas pages

- **Disease cohort memberships** *(association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases)*: [premature menopause](/atlas/disease/premature-menopause/)