Autosomal recessive spinocerebellar ataxia 11

Summary

Autosomal recessive spinocerebellar ataxia 11 (MONDO:0013645) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Cohort genes: 1
• ClinVar variants: 5
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000617	Abnormality of ocular smooth pursuit	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001272	Cerebellar atrophy	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0002070	Limb ataxia	Very frequent (80-99%)
HP:0002078	Truncal ataxia	Very frequent (80-99%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0002317	Unsteady gait	Frequent (30-79%)
HP:0007979	Gaze-evoked horizontal nystagmus	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive spinocerebellar ataxia 11
Mondo ID	MONDO:0013645
OMIM	614229
Orphanet	284271
DOID	DOID:0080063
UMLS	C5190803
MedGen	1681191
GARD	0017312
Is cancer (heuristic)	no

Also known as: autosomal recessive spinocerebellar ataxia 11 · autosomal recessive spinocerebellar ataxia type 11 · autosomal recessive syndromic cerebellar ataxia caused by mutation in SYT14 · SCAR11 · spinocerebellar ataxia, autosomal recessive 11 · spinocerebellar ataxia, autosomal recessive type 11 · SYT14 autosomal recessive syndromic cerebellar ataxia

Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive cerebellar ataxia › autosomal recessive syndromic cerebellar ataxia › autosomal recessive spinocerebellar ataxia 11

Related subtypes (6): autosomal recessive cerebellar ataxia-saccadic intrusion syndrome, peroxisome biogenesis disorder 4B, ataxia - oculomotor apraxia type 4, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, Gemignani syndrome, cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome

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

5 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30861	NM_001146262.4(SYT14):c.1316G>A (p.Gly439Asp)	SYT14	Pathogenic	no assertion criteria provided
212360	NM_001146262.4(SYT14):c.672AGA[1] (p.Glu225del)	SYT14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3578431	NM_001146262.4(SYT14):c.541C>G (p.Pro181Ala)	SYT14	Uncertain significance	criteria provided, single submitter
805534	NM_001146262.4(SYT14):c.392C>G (p.Pro131Arg)	SYT14	Uncertain significance	criteria provided, multiple submitters, no conflicts
130533	NM_001146262.4(SYT14):c.1419T>C (p.Tyr473=)	SYT14	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
SYT14	Supportive	Autosomal recessive	autosomal recessive spinocerebellar ataxia 11	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SYT14	Orphanet:284271	Autosomal recessive cerebellar ataxia-psychomotor delay syndrome

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
SYT14	HGNC:23143	ENSG00000143469	Q8NB59	Synaptotagmin-14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SYT14	Synaptotagmin-14	May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SYT14	Other/Unknown	no		C2_dom, C2_domain_sf, SYT14/14L/16

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
cortical plate	1
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SYT14	89	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, cortical plate, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SYT14	572

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SYT14	Q8NB59	65.50

Function

Pathway analysis

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

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SYT14	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SYT14

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)
SYT14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.