spondyloepimetaphyseal dysplasia, Krakow type

disease

On this page

Also known as SEMDK

Summary

spondyloepimetaphyseal dysplasia, Krakow type (MONDO:0032571) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepimetaphyseal dysplasia, Krakow type
Mondo ID	MONDO:0032571
OMIM	618162
UMLS	C4748455
MedGen	1648323
GARD	0025705
Is cancer (heuristic)	no

Also known as: SEMDK

Data availability: 7 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › spondyloepimetaphyseal dysplasia › spondyloepimetaphyseal dysplasia, Krakow type

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

7 retrieved; paginated sample, class counts are floors:

4 benign, 1 likely pathogenic, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
587366	NM_001366686.3(SIK3):c.559C>T (p.Arg187Cys)	SIK3	Pathogenic	no assertion criteria provided
3024353	NM_001366686.3(SIK3):c.950T>G (p.Met317Arg)	SIK3	Likely pathogenic	criteria provided, single submitter
1332964	NM_001366686.3(SIK3):c.3551C>G (p.Pro1184Arg)	SIK3	Benign	criteria provided, multiple submitters, no conflicts
1332965	NM_001366686.3(SIK3):c.2315+45C>A	SIK3	Benign	criteria provided, multiple submitters, no conflicts
1332966	NM_001366686.3(SIK3):c.1953-11C>T	SIK3	Benign	criteria provided, multiple submitters, no conflicts
1332967	NM_001366686.3(SIK3):c.1582-37A>G	SIK3	Benign	criteria provided, multiple submitters, no conflicts
768487	NM_001366686.3(SIK3):c.3292G>A (p.Ala1098Thr)	SIK3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SIK3	Moderate	Autosomal recessive	spondyloepimetaphyseal dysplasia, Krakow type	5

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
SIK3	HGNC:29165	ENSG00000160584	Q9Y2K2	Serine/threonine-protein kinase SIK3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SIK3	Serine/threonine-protein kinase SIK3	Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor.

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)
SIK3	Kinase	yes		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
corpus callosum	1
lateral globus pallidus	1
lateral nuclear group of thalamus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SIK3	290	ubiquitous	marker	lateral globus pallidus, corpus callosum, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SIK3	1,742

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SIK3	Q9Y2K2	5

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
positive regulation of TORC2 signaling	1	2106.5×	0.002	SIK3
positive regulation of TORC1 signaling	1	295.6×	0.008	SIK3
microtubule cytoskeleton organization	1	121.2×	0.014	SIK3
protein phosphorylation	1	68.0×	0.018	SIK3
intracellular signal transduction	1	38.1×	0.026	SIK3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SIK3	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SIK3	25	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	SIK3
FEDRATINIB	4	SIK3
RUXOLITINIB	4	SIK3
DABRAFENIB	4	SIK3
VANDETANIB	4	SIK3
BOSUTINIB	4	SIK3
DASATINIB	4	SIK3
MIDOSTAURIN	4	SIK3
CRENOLANIB	3	SIK3
SARACATINIB	3	SIK3
CANERTINIB	3	SIK3
LESTAURTINIB	3	SIK3
ZOTIRACICLIB	2	SIK3
TANZISERTIB	2	SIK3
OSI-632	2	SIK3
SONOLISIB	2	SIK3
AT-9283	2	SIK3
MILCICLIB	2	SIK3
UCN-01	2	SIK3
KW-2449	1	SIK3
AZD-7762	1	SIK3
XL-019	1	SIK3
PF-03814735	1	SIK3
CYC-116	1	SIK3
Y-39983	1	SIK3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SIK3	173	Binding:173

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SIK3	173

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

25 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)
MOMELOTINIB	4	SIK3
FEDRATINIB	4	SIK3
RUXOLITINIB	4	SIK3
DABRAFENIB	4	SIK3
VANDETANIB	4	SIK3
BOSUTINIB	4	SIK3
DASATINIB	4	SIK3
MIDOSTAURIN	4	SIK3
CRENOLANIB	3	SIK3
SARACATINIB	3	SIK3
CANERTINIB	3	SIK3
LESTAURTINIB	3	SIK3
ZOTIRACICLIB	2	SIK3
TANZISERTIB	2	SIK3
OSI-632	2	SIK3
SONOLISIB	2	SIK3
AT-9283	2	SIK3
MILCICLIB	2	SIK3
UCN-01	2	SIK3
KW-2449	1	SIK3
AZD-7762	1	SIK3
XL-019	1	SIK3
PF-03814735	1	SIK3
CYC-116	1	SIK3
Y-39983	1	SIK3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SIK3
B	Phased (≥1) drug, not yet approved	0
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.

Cohort genes: SIK3