Spastic ataxia 9, autosomal recessive

Summary

Spastic ataxia 9, autosomal recessive (MONDO:0032753) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic ataxia 9, autosomal recessive
Mondo ID	MONDO:0032753
OMIM	618438
UMLS	C5193100
MedGen	1680026
GARD	0025734
Is cancer (heuristic)	no

Also known as: SPAX9

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

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › atactic disorder › hereditary ataxia › spastic ataxia › spastic ataxia 9, autosomal recessive

Related subtypes (5): spastic ataxia 2, spasticity-ataxia-gait anomalies syndrome, autosomal dominant spastic ataxia, autosomal recessive spastic ataxia, spastic ataxia 10, autosomal recessive

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
632545	NM_007236.5(CHP1):c.52AAG[1] (p.Lys19del)	CHP1	Pathogenic	no assertion criteria provided

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
CHORDC1	Limited	Unknown	spastic ataxia 9, autosomal recessive
CHP1	Limited	Unknown	spastic ataxia 9, autosomal recessive

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CHORDC1	HGNC:14525	ENSG00000110172	Q9UHD1	Cysteine and histidine-rich domain-containing protein 1	gencc,clinvar
CHP1	HGNC:17433	ENSG00000187446	Q99653	Calcineurin B homologous protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHORDC1	Cysteine and histidine-rich domain-containing protein 1	Regulates centrosome duplication, probably by inhibiting the kinase activity of ROCK2.
CHP1	Calcineurin B homologous protein 1	Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHORDC1	Other/Unknown	no		CHORD_dom, CS_dom, HSP20-like_chaperone
CHP1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, Calcineurin_B_homologous

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	1
endometrium	1
ventricular zone	1
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHORDC1	134	ubiquitous	marker	corpus callosum, endometrium, ventricular zone
CHP1	290	ubiquitous	marker	colonic mucosa, mucosa of sigmoid colon, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHP1	2,051
CHORDC1	1,520

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHP1	Q99653	4
CHORDC1	Q9UHD1	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Hyaluronan degradation	1	713.8×	0.001	CHP1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
membrane docking	1	8426.0×	0.002	CHP1
negative regulation of protein autophosphorylation	1	4213.0×	0.002	CHP1
positive regulation of protein transport	1	4213.0×	0.002	CHP1
negative regulation of phosphatase activity	1	2808.7×	0.002	CHP1
positive regulation of sodium:proton antiporter activity	1	2808.7×	0.002	CHP1
positive regulation of phospholipid biosynthetic process	1	2106.5×	0.002	CHP1
positive regulation of glycoprotein biosynthetic process	1	1053.2×	0.004	CHP1
regulation of cellular response to heat	1	526.6×	0.005	CHORDC1
negative regulation of protein import into nucleus	1	468.1×	0.005	CHP1
centrosome duplication	1	468.1×	0.005	CHORDC1
negative regulation of calcineurin-NFAT signaling cascade	1	468.1×	0.005	CHP1
negative regulation of protein kinase activity	1	421.3×	0.005	CHP1
regulation of centrosome duplication	1	366.4×	0.005	CHORDC1
cellular response to acidic pH	1	366.4×	0.005	CHP1
membrane fusion	1	312.1×	0.005	CHP1
regulation of intracellular pH	1	300.9×	0.005	CHP1
negative regulation of protein phosphorylation	1	290.6×	0.005	CHP1
positive regulation of protein targeting to membrane	1	280.9×	0.005	CHP1
microtubule bundle formation	1	255.3×	0.005	CHP1
protein export from nucleus	1	255.3×	0.005	CHP1
membrane organization	1	255.3×	0.005	CHP1
obsolete negative regulation of NF-kappaB transcription factor activity	1	179.3×	0.007	CHP1
cytoplasmic microtubule organization	1	172.0×	0.007	CHP1
negative regulation of protein ubiquitination	1	142.8×	0.008	CHP1
potassium ion transport	1	95.8×	0.012	CHP1
small GTPase-mediated signal transduction	1	91.6×	0.012	CHP1
protein folding	1	51.7×	0.020	CHORDC1
protein stabilization	1	33.4×	0.030	CHP1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHORDC1	0	0
CHP1	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
CHP1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	CHORDC1, CHP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CHORDC1	0	—
CHP1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.