CDKL5 disorder: genes and variants
CDKL5 disorder is linked to 1 analyzed protein (CDKL5). 32 DNA variants are known to cause it; 34 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to CDKL5 disorder
CDKL5: Cyclin-dependent kinase-like 5
It phosphorylates neuronal substrates involved in synapse development, cytoskeletal organization, and signaling during early brain maturation. Loss-of-function variants cause CDKL5 deficiency disorder with very early epilepsy and severe developmental impairment.
32 disease-causing and 34 uncertain variants in CDKL5 are linked to CDKL5 disorder.
Where CDKL5 disorder variants cluster
- CDKL5 Protein kinase (positions 13–297): 31 of 32 disease-causing changes, 3.3× more than its size predicts.
Known disease-causing variants in CDKL5 disorder
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CDKL5 G20V | 20 | Protein kinase | Disease-causing (★★★) |
| CDKL5 I72T | 72 | Protein kinase | Disease-causing (★★★) |
| CDKL5 C152R | 152 | Protein kinase | Disease-causing (★★★) |
| CDKL5 A157P | 157 | Protein kinase | Disease-causing (★★★) |
| CDKL5 R178Q | 178 | Protein kinase | Disease-causing (★★★) |
| CDKL5 R178W | 178 | Protein kinase | Disease-causing (★★★) |
| CDKL5 A157V | 157 | Protein kinase | Disease-causing (★★★) |
| CDKL5 G22E | 22 | Protein kinase | Disease-causing (★★★) |
| CDKL5 L97P | 97 | Protein kinase | Disease-causing (★★★) |
| CDKL5 D193V | 193 | Protein kinase | Disease-causing (★★★) |
| CDKL5 Q219P | 219 | Protein kinase | Disease-causing (★★★) |
| CDKL5 F13S | 13 | Protein kinase | Disease-causing (★★★) |
| CDKL5 T288R | 288 | Protein kinase | Disease-causing (★★★) |
| CDKL5 V718M | 718 | Disease-causing (★★★) | |
| CDKL5 A40V | 40 | Protein kinase | Disease-causing (★★★) |
| CDKL5 L182P | 182 | Protein kinase | Disease-causing (★★★) |
| CDKL5 G20D | 20 | Protein kinase | Disease-causing (★★) |
| CDKL5 C152F | 152 | Protein kinase | Disease-causing (★★) |
| CDKL5 W176C | 176 | Protein kinase | Disease-causing (★★) |
| CDKL5 W176R | 176 | Protein kinase | Disease-causing (★★) |
| CDKL5 R178P | 178 | Protein kinase | Disease-causing (★★) |
| CDKL5 E21G | 21 | Protein kinase | Disease-causing (★★) |
| CDKL5 H127Y | 127 | Protein kinase | Disease-causing (★★) |
| CDKL5 G198D | 198 | Protein kinase | Disease-causing (★★) |
| CDKL5 G213E | 213 | Protein kinase | Disease-causing (★★) |
| CDKL5 R59P | 59 | Protein kinase | Disease-causing (★★) |
| CDKL5 V27A | 27 | Protein kinase | Disease-causing (★★) |
| CDKL5 K42R | 42 | Protein kinase | Disease-causing (★★) |
| CDKL5 L271P | 271 | Protein kinase | Disease-causing (★★) |
| CDKL5 I72N | 72 | Protein kinase | Disease-causing (★) |
| CDKL5 D153G | 153 | Protein kinase | Disease-causing (★) |
| CDKL5 R175S | 175 | Protein kinase | Disease-causing (★) |
Uncertain variants in CDKL5 disorder that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| CDKL5 D153V | 153 | Protein kinase | Uncertain (★★) | +6: 3 other pathogenic changes within 3 positions; D153G at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| CDKL5 W176G | 176 | Protein kinase | Uncertain (★) | +6: 6 other pathogenic changes within 3 positions; W176C at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
Which prediction tools work for CDKL5 disorder
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- MutPred2: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- EVE: 98 out of 100
- AlphaMissense: 97 out of 100
- PolyPhen-2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 77 out of 100
Same protein, different disease
- Angelman syndrome-like is also caused by CDKL5 variants; they fall partly in the same places as the CDKL5 disorder variants (41 disease-causing).
Diseases related to CDKL5 disorder
- Rett syndrome, also linked to CDKL5
- Angelman syndrome-like, also linked to CDKL5
- Angelman syndrome, also linked to CDKL5
- Autism, also linked to CDKL5
- Infantile spasms, also linked to CDKL5
Frequently asked questions
Which genes are linked to CDKL5 disorder?
In CATVariant, CDKL5 disorder is linked to 1 analyzed protein: CDKL5 (Cyclin-dependent kinase-like 5).
How many genetic variants are linked to CDKL5 disorder?
109 variants: 32 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 34 are of uncertain significance or have conflicting reports.
Which uncertain variants in CDKL5 disorder look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example CDKL5 D153V and CDKL5 W176G. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for CDKL5 disorder?
Among tools not trained on clinical labels, EVE separates this disease's known disease-causing variants from harmless ones best (AUROC 0.98, based on 24 disease-causing and 21 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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