Al Kaissi syndrome

Summary

Al Kaissi syndrome (MONDO:0044324) is a disease caused by CDK10 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CDK10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Al Kaissi syndrome
Mondo ID	MONDO:0044324
OMIM	617694
UMLS	C4540156
MedGen	1611968
GARD	0025894
Is cancer (heuristic)	no

Also known as: ALKAS

Data availability: 41 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › autosomal recessive syndromic intellectual disability › Al Kaissi syndrome

Related subtypes (6): Cohen syndrome, intellectual disability-hypotonia-spasticity-sleep disorder syndrome, intellectual disability, autosomal recessive 53, short stature-brachydactyly-obesity-global developmental delay syndrome, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, intellectual developmental disorder with neuropsychiatric features

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

41 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 12 pathogenic, 7 likely pathogenic, 6 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1172607	NM_052988.5(CDK10):c.870_871del (p.Trp291fs)	CDK10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1176670	NM_052988.5(CDK10):c.520_521del (p.Lys174fs)	CDK10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802200	NM_052988.5(CDK10):c.716_728del (p.Leu239fs)	CDK10	Pathogenic	criteria provided, single submitter
2580182	NM_052988.5(CDK10):c.625CTG[1] (p.Leu211del)	CDK10	Pathogenic	criteria provided, single submitter
2580183	NM_052988.5(CDK10):c.792G>A (p.Pro264=)	CDK10	Pathogenic	criteria provided, single submitter
2580185	NM_052988.5(CDK10):c.87+5G>A	CDK10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2580186	NM_052988.4:c.(87+1_88-1)_(232+1_233-1)del	CDK10	Pathogenic	criteria provided, single submitter
2580187	NM_052988.5(CDK10):c.161-1G>C	CDK10	Pathogenic	criteria provided, single submitter
2580188	NM_052988.5(CDK10):c.226A>T (p.Lys76Ter)	CDK10	Pathogenic	criteria provided, single submitter
2580189	NM_052988.5(CDK10):c.452T>C (p.Leu151Pro)	CDK10	Pathogenic	criteria provided, single submitter
2580190	NM_052988.5(CDK10):c.461T>C (p.Leu154Pro)	CDK10	Pathogenic	criteria provided, single submitter
2580191	NM_052988.5(CDK10):c.503del (p.Asn168fs)	CDK10	Pathogenic	criteria provided, single submitter
440754	NM_052988.5(CDK10):c.609-1G>A	CDK10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
440755	NM_052988.5(CDK10):c.88-870_232+368del	CDK10	Pathogenic	no assertion criteria provided
440757	NM_052988.5(CDK10):c.608+1G>A	CDK10	Pathogenic	criteria provided, multiple submitters, no conflicts
916087	NM_052988.5(CDK10):c.664_665del (p.Met222fs)	CDK10	Pathogenic	criteria provided, multiple submitters, no conflicts
986936	NM_052988.5(CDK10):c.729del (p.Glu244fs)	CDK10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
992884	NM_052988.5(CDK10):c.24C>A (p.Cys8Ter)	CDK10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1684275	NM_052988.5(CDK10):c.299_300dup (p.Leu101fs)	CDK10	Likely pathogenic	criteria provided, single submitter
3235695	NM_052988.5(CDK10):c.669G>A (p.Trp223Ter)	CDK10	Likely pathogenic	no assertion criteria provided
3779035	NM_052988.5(CDK10):c.613C>T (p.Arg205Ter)	CDK10	Likely pathogenic	criteria provided, single submitter
4077143	NM_052988.5(CDK10):c.161-2A>G	CDK10	Likely pathogenic	criteria provided, single submitter
440756	NM_052988.5(CDK10):c.139del (p.Glu47fs)	CDK10	Likely pathogenic	criteria provided, single submitter
4686730	NM_052988.5(CDK10):c.846C>G (p.Tyr282Ter)	CDK10	Likely pathogenic	criteria provided, single submitter
813896	NM_052988.5(CDK10):c.550_556del (p.Leu184fs)	CDK10	Likely pathogenic	criteria provided, single submitter
1027754	NM_052988.5(CDK10):c.51T>G (p.Arg17=)	CDK10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
402152	NM_052988.5(CDK10):c.1070G>A (p.Arg357His)	CDK10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027755	NM_052988.5(CDK10):c.527G>C (p.Cys176Ser)	CDK10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027756	NM_052988.5(CDK10):c.661G>A (p.Asp221Asn)	CDK10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027757	NM_052988.5(CDK10):c.263C>G (p.Thr88Arg)	CDK10	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CDK10	Strong	Autosomal recessive	Al Kaissi syndrome	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDK10	HGNC:1770	ENSG00000185324	Q15131	Cyclin-dependent kinase 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDK10	Cyclin-dependent kinase 10	Cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and positively controls its proteasomal degradation (in cells).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDK10	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left lobe of thyroid gland	1
right lobe of thyroid gland	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDK10	286	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDK10	1,293

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDK10	Q15131	86.27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
traversing start control point of mitotic cell cycle	1	4213.0×	0.002	CDK10
regulation of cell cycle G2/M phase transition	1	2407.4×	0.002	CDK10
peptidyl-threonine phosphorylation	1	887.0×	0.002	CDK10
negative regulation of cilium assembly	1	802.5×	0.002	CDK10
cell projection organization	1	374.5×	0.004	CDK10
regulation of actin cytoskeleton organization	1	157.5×	0.008	CDK10
positive regulation of MAPK cascade	1	80.6×	0.014	CDK10
negative regulation of cell population proliferation	1	42.1×	0.024	CDK10

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDK10	3	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CDK10
AT-9283	2	CDK10
INDIRUBIN	2	CDK10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CDK10	59	Binding:59

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CDK10	2.7.11.22	cyclin-dependent kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

3 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	CDK10
AT-9283	2	CDK10
INDIRUBIN	2	CDK10

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	CDK10
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.