Apraxia

Summary

Apraxia (MONDO:0000665) is a disease with 3 cohort genes and 8 clinical trials.

At a glance

• Cohort genes: 3
• ClinVar variants: 2
• Clinical trials: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	apraxia
Mondo ID	MONDO:0000665
MeSH	D001072
DOID	DOID:0060135
ICD-10-CM	R48.2
ICD-11	986651951
NCIT	C180557
UMLS	C0003635
MedGen	8166
Is cancer (heuristic)	no

Also known as: Apraxias · dyspraxia

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › perceptual disorders › apraxia

Related subtypes (8): vestibular disorder, agnosia, inherited retinal dystrophy, vision disorder, hearing disorder, auditory perceptual disorders, allesthesia, hallucinogen-persisting perception disorder

Subtypes (2): gait apraxia, ideomotor apraxia

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

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
812923	NC_000005.10:g.139189727_139201554del	SIL1	Pathogenic	no assertion criteria provided
2570672	NM_022113.6(KIF13A):c.3364A>G (p.Lys1122Glu)	KIF13A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 8 · 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
SUFU	Strong	Autosomal dominant	ocular motor apraxia, Cogan type	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUFU	Orphanet:2495	Meningioma
SUFU	Orphanet:251858	Medulloblastoma with extensive nodularity
SUFU	Orphanet:251863	Desmoplastic/nodular medulloblastoma
SUFU	Orphanet:263662	Familial multiple meningioma
SUFU	Orphanet:280200	Microform holoprosencephaly
SUFU	Orphanet:377	Gorlin syndrome
SUFU	Orphanet:475	Isolated Joubert syndrome
SIL1	Orphanet:559	Marinesco-Sjögren syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	gencc
KIF13A	HGNC:14566	ENSG00000137177	Q9H1H9	Kinesin-like protein KIF13A	clinvar
SIL1	HGNC:24624	ENSG00000120725	Q9H173	Nucleotide exchange factor SIL1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.
KIF13A	Kinesin-like protein KIF13A	Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome bi…
SIL1	Nucleotide exchange factor SIL1	Required for protein translocation and folding in the endoplasmic reticulum (ER).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
KIF13A	Other/Unknown	no		FHA_dom, Kinesin_motor_dom, SMAD_FHA_dom_sf
SIL1	Other/Unknown	no		ARM-like, Nucleotide_exch_fac_Fes1, ARM-type_fold

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
kidney epithelium	1
upper arm skin	1
vena cava	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
tendon of biceps brachii	1
body of pancreas	1
islet of Langerhans	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava
KIF13A	276	ubiquitous	marker	tendon of biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii
SIL1	251	ubiquitous	marker	islet of Langerhans, body of pancreas, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SIL1	4,196
SUFU	2,188
KIF13A	1,115

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SUFU	Q9UMX1	10
SIL1	Q9H173	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KIF13A	Q9H1H9	66.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chaperonin-mediated protein folding	1	150.3×	0.015	KIF13A
Association of TriC/CCT with target proteins during biosynthesis	1	146.4×	0.015	KIF13A
Protein folding	1	129.8×	0.015	KIF13A
Degradation of GLI1 by the proteasome	1	112.0×	0.015	SUFU
Degradation of GLI2 by the proteasome	1	112.0×	0.015	SUFU
GLI3 is processed to GLI3R by the proteasome	1	112.0×	0.015	SUFU
Signaling by Hedgehog	1	92.1×	0.015	SUFU
Hedgehog ‘off’ state	1	89.2×	0.015	SUFU
Hedgehog ‘on’ state	1	79.3×	0.015	SUFU
Metabolism of proteins	1	6.2×	0.171	KIF13A
Signal Transduction	1	5.1×	0.187	SUFU

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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 cellular response to drug	1	5617.3×	0.003	SUFU
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	2808.7×	0.003	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	2808.7×	0.003	SUFU
maintenance of protein localization in organelle	1	2808.7×	0.003	SUFU
intracellular protein transport	2	43.2×	0.004	KIF13A, SIL1
plus-end-directed vesicle transport along microtubule	1	936.2×	0.005	KIF13A
cotranslational protein targeting to membrane	1	561.7×	0.008	SIL1
vesicle cargo loading	1	468.1×	0.008	KIF13A
negative regulation of protein import into nucleus	1	312.1×	0.010	SUFU
negative regulation of ubiquitin-dependent protein catabolic process	1	280.9×	0.010	SUFU
dorsal/ventral neural tube patterning	1	267.5×	0.010	SUFU
melanosome organization	1	216.1×	0.011	KIF13A
coronary vasculature development	1	208.1×	0.011	SUFU
aorta development	1	187.2×	0.011	SUFU
Golgi to plasma membrane protein transport	1	175.5×	0.011	KIF13A
ventricular septum development	1	165.2×	0.011	SUFU
negative regulation of smoothened signaling pathway	1	151.8×	0.011	SUFU
skin development	1	147.8×	0.011	SUFU
regulation of cytokinesis	1	140.4×	0.011	KIF13A
endosome to lysosome transport	1	112.3×	0.013	KIF13A
microtubule-based movement	1	98.5×	0.014	KIF13A
negative regulation of osteoblast differentiation	1	98.5×	0.014	SUFU
heart looping	1	89.2×	0.015	SUFU
neural tube closure	1	62.4×	0.020	SUFU
spermatid development	1	48.4×	0.025	SUFU
protein folding	1	34.5×	0.033	SIL1
cell division	1	15.4×	0.071	KIF13A
regulation of DNA-templated transcription	1	10.5×	0.099	SUFU
negative regulation of transcription by RNA polymerase II	1	5.9×	0.165	SUFU
signal transduction	1	5.3×	0.176	SUFU

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SUFU	0	0
KIF13A	0	0
SIL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SUFU	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	SUFU, KIF13A, SIL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SUFU	1	—
KIF13A	0	—
SIL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01046760	Not specified	UNKNOWN	Scholar Performance and Praxis Assessment in Children With Rolandic Epilepsy
NCT01507636	Not specified	COMPLETED	Occupational Therapy in Patients With Multiple Sclerosis
NCT02199093	Not specified	COMPLETED	Functional Rehabilitation of Upper Limb Apraxia in Patients Poststroke
NCT02517333	Not specified	UNKNOWN	Exploring the Impact and Feasibility of a Pathway to Sport and Long-term Participation in Young People
NCT03185234	Not specified	COMPLETED	Rehabilitating (Stroke-induced) Apraxia With Direct Current Stimulation
NCT03353623	Not specified	COMPLETED	Immersive Virtual Environments and Wearable Haptic Devices in Rehabilitation of Children With Neuromotor Impairments
NCT04044911	Not specified	COMPLETED	Trial Using CogWatch for Tea Making Training in Stroke Apraxia and Action Disorganisation Syndrome
NCT04122820	Not specified	UNKNOWN	Ambulatory Screening for Specific Learning Disabilities (SLD) and Developmental Coordination Disorder (DCD).