KIF1A related neurological disorder

Summary

KIF1A related neurological disorder (MONDO:0700055) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	KIF1A related neurological disorder
Mondo ID	MONDO:0700055
Is cancer (heuristic)	no

Also known as: KAND · KIF1A neurological disorder · neurological disorder caused by mutation in KIF1A · neurological disorder caused by variation in KIF1A

Data availability: 11 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › KIF1A related neurological disorder

Related subtypes (71): congenital nervous system disorder, central nervous system disorder, autoimmune disorder of the nervous system, cranial nerve neuropathy, peripheral nervous system disorder, neuronitis, diplegia of upper limb, retinal disorder, developmental disability, restless legs syndrome, movement disorder, toxic encephalopathy, Barre-Lieou syndrome, Gerstmann syndrome, drug-induced akathisia, drug-induced dyskinesia, stiff-person syndrome, Worster-Drought syndrome, corneal-cerebellar syndrome, pachygyria-intellectual disability-epilepsy syndrome, porencephaly-cerebellar hypoplasia-internal malformations syndrome, symmetrical thalamic calcifications, neonatal brainstem dysfunction, primary orthostatic hypotension, rippling muscle disease with myasthenia gravis, periodic paralysis, qualitative or quantitative protein defects in neuromuscular diseases, specific learning disability, cerebellar hypoplasia-tapetoretinal degeneration syndrome, locked-in syndrome, dopa-responsive dystonia, idiopathic recurrent stupor, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, spontaneous periodic hypothermia, Sydenham chorea, duplication of the pituitary gland, Balint syndrome, paraneoplastic neurologic syndrome, persistent idiopathic facial pain, serotonin syndrome, hypothalamic adipsic hypernatraemia syndrome, exercise-induced malignant hyperthermia, perineural cyst, neuromuscular disease, neuromyelitis optica, AL amyloidosis, AA amyloidosis, neuroleptic malignant syndrome, infectious disorder of the nervous system, central nervous system malformation, synaptopathy, nervous system neoplasm, sensory ganglionopathy, radiculitis, wet beriberi, perceptual disorders, prepubertal anorexia nervosa, neurocutaneous syndrome, neurovascular disorder, Wallerian degeneration, nervous system injury, neurosarcoidosis, neuroendocrine disorder, tubulinopathy, atactic disorder, hereditary neurological disease, meningitis-retention syndrome, neurological pain disorder, neurodevelopmental disorder, post 5-alpha-reductase inhibitors treatment syndrome, post-selective serotonin reuptake inhibitor sexual dysfunction

Subtypes (3): hereditary spastic paraplegia 30, neuropathy, hereditary sensory, type 2C, intellectual disability, autosomal dominant 9

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

11 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 benign/likely benign, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
426934	NM_001244008.2(KIF1A):c.37C>T (p.Arg13Cys)	KIF1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428604	NM_001244008.2(KIF1A):c.914C>T (p.Pro305Leu)	KIF1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4531853	NM_001244008.2(KIF1A):c.596_597insAAGTCCTGAGTCCACCTG (p.Gly199_Asn200insSerProGluSerThrTrp)	KIF1A	Pathogenic	criteria provided, single submitter
4531852	NM_001244008.2(KIF1A):c.748G>C (p.Ala250Pro)	KIF1A	Likely pathogenic	criteria provided, single submitter
1937610	NM_001244008.2(KIF1A):c.3391G>A (p.Asp1131Asn)	KIF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
245928	NM_001244008.2(KIF1A):c.1040A>G (p.Tyr347Cys)	KIF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
497030	NM_001244008.2(KIF1A):c.2721GGA[12] (p.Glu917dup)	KIF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1428612	NM_001244008.2(KIF1A):c.2977+4C>T	KIF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3254582	NM_001244008.2(KIF1A):c.4475C>A (p.Thr1492Asn)	KIF1A	Uncertain significance	criteria provided, single submitter
3365163	NM_001244008.2(KIF1A):c.2707G>A (p.Glu903Lys)	KIF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
284274	NM_001244008.2(KIF1A):c.2721GGA[10] (p.Glu917del)	KIF1A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIF1A	Orphanet:101010	Autosomal spastic paraplegia type 30
KIF1A	Orphanet:662367	NESCAV syndrome
KIF1A	Orphanet:970	Hereditary sensory and autonomic neuropathy type 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
KIF1A	HGNC:888	ENSG00000130294	Q12756	Kinesin-like protein KIF1A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF1A	Kinesin-like protein KIF1A	Kinesin motor with a plus-end-directed microtubule motor activity.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF1A	Scaffold/PPI	no	5.6.1.3	FHA_dom, Kinesin_motor_dom, PH_domain

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
parietal lobe	1
postcentral gyrus	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF1A	198	broad	marker	right frontal lobe, postcentral gyrus, parietal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF1A	2,833

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF1A	Q12756	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Kinesins	1	178.4×	0.019	KIF1A
Golgi-to-ER retrograde transport	1	132.8×	0.019	KIF1A
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.019	KIF1A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.019	KIF1A
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.024	KIF1A
Membrane Trafficking	1	37.1×	0.029	KIF1A
Hemostasis	1	36.0×	0.029	KIF1A
Vesicle-mediated transport	1	34.8×	0.029	KIF1A

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
dense core granule cytoskeletal transport	1	4213.0×	7e-04	KIF1A
anterograde neuronal dense core vesicle transport	1	4213.0×	7e-04	KIF1A
retrograde neuronal dense core vesicle transport	1	3370.4×	7e-04	KIF1A
regulation of dendritic spine development	1	1685.2×	0.001	KIF1A
regulation of dendritic spine morphogenesis	1	842.6×	0.002	KIF1A
anterograde axonal transport	1	581.1×	0.002	KIF1A
vesicle-mediated transport	1	96.3×	0.010	KIF1A

Therapeutics

Drug target analysis

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

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
KIF1A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KIF1A	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIF1A	5.6.1.3	plus-end-directed kinesin ATPase

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

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	1	KIF1A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KIF1A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.