Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome

Summary

Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome (MONDO:0044726) is a disease caused by SLC30A9 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC30A9 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome
Mondo ID	MONDO:0044726
OMIM	617595
Orphanet	505242
UMLS	C4539828
MedGen	1621949
GARD	0017943
Is cancer (heuristic)	no

Also known as: BILAPES · Cerebrorenal syndrome, Perez type

Data availability: 19 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › renal tubule disorder › inherited renal tubular disease › psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome

Related subtypes (27): cranioectodermal dysplasia, cystinuria, hereditary renal hypouricemia, nephrogenic diabetes insipidus-intracranial calcification syndrome, Gitelman syndrome, nephrogenic syndrome of inappropriate antidiuresis, oculocerebrorenal syndrome, RHYNS syndrome, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, autosomal recessive proximal renal tubular acidosis, EAST syndrome, familial juvenile hyperuricemic nephropathy type 2, hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome, Bartter syndrome, Dent disease, nephrogenic diabetes insipidus, autosomal dominant proximal renal tubular acidosis, Senior-Loken syndrome, familial primary hypomagnesemia, mitochondrial DNA depletion syndrome, hepatocerebrorenal form, Jeune syndrome, nephronophthisis, pseudohypoaldosteronism type 1, Senior-Boichis syndrome, pseudohypoparathyroidism, HELIX syndrome, inherited Fanconi renotubular 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

19 retrieved; paginated sample, class counts are floors:

6 benign, 6 uncertain significance, 3 likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1300169	NM_006345.4(SLC30A9):c.86_87dup (p.Cys30fs)	SLC30A9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3769130	NM_006345.4(SLC30A9):c.143C>A (p.Ser48Ter)	SLC30A9	Pathogenic	criteria provided, single submitter
431049	NM_006345.4(SLC30A9):c.1049_1051del (p.Ala350del)	SLC30A9	Pathogenic	criteria provided, single submitter
1333196	NM_006345.4(SLC30A9):c.840+1G>A	SLC30A9	Likely pathogenic	criteria provided, single submitter
1723220	NM_006345.4(SLC30A9):c.543G>A (p.Trp181Ter)	SLC30A9	Likely pathogenic	criteria provided, single submitter
3377089	NM_006345.4(SLC30A9):c.841-1G>A	SLC30A9	Likely pathogenic	criteria provided, single submitter
1300159	NM_006345.4(SLC30A9):c.40del (p.Ser14fs)	SLC30A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1878602	NM_006345.4(SLC30A9):c.947G>A (p.Gly316Asp)	SLC30A9	Uncertain significance	criteria provided, single submitter
3061863	NM_006345.4(SLC30A9):c.1145-8A>G	SLC30A9	Uncertain significance	criteria provided, single submitter
3590575	NM_006345.4(SLC30A9):c.1216A>G (p.Ile406Val)	SLC30A9	Uncertain significance	criteria provided, single submitter
3590576	NM_006345.4(SLC30A9):c.1256A>G (p.Asn419Ser)	SLC30A9	Uncertain significance	criteria provided, single submitter
3892469	NM_006345.4(SLC30A9):c.1361T>G (p.Ile454Ser)	SLC30A9	Uncertain significance	criteria provided, single submitter
3892470	NM_006345.4(SLC30A9):c.1635A>G (p.Glu545=)	SLC30A9	Uncertain significance	criteria provided, single submitter
1242979	NM_006345.4(SLC30A9):c.9C>G (p.Pro3=)	SLC30A9	Benign	criteria provided, multiple submitters, no conflicts
1333130	NM_006345.4(SLC30A9):c.148A>G (p.Met50Val)	SLC30A9	Benign	criteria provided, multiple submitters, no conflicts
1333131	NM_006345.4(SLC30A9):c.274+38C>G	SLC30A9	Benign	criteria provided, multiple submitters, no conflicts
1333132	NM_006345.4(SLC30A9):c.289A>G (p.Thr97Ala)	SLC30A9	Benign	criteria provided, multiple submitters, no conflicts
1333133	NM_006345.4(SLC30A9):c.366C>A (p.Gly122=)	SLC30A9	Benign	criteria provided, multiple submitters, no conflicts
1333134	NM_006345.4(SLC30A9):c.527+35A>G	SLC30A9	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SLC30A9	Strong	Autosomal recessive	psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC30A9	Orphanet:505242	Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy 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
SLC30A9	HGNC:1329	ENSG00000014824	Q6PML9	Proton-coupled zinc antiporter SLC30A9, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC30A9	Proton-coupled zinc antiporter SLC30A9, mitochondrial	Mitochondrial proton-coupled zinc ion antiporter mediating the export of zinc from the mitochondria and involved in zinc homeostasis, zinc mobilization as well as mitochondrial morphology and health.

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)
SLC30A9	Other/Unknown	no		Cation_efflux, DNA-bd_dom_put_sf, Cation_efflux_TMD_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
calcaneal tendon	1
cortical plate	1
germinal epithelium of ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC30A9	300	ubiquitous	marker	cortical plate, calcaneal tendon, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC30A9	2,147

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC30A9	Q6PML9	1

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
zinc ion transport	1	1532.0×	0.003	SLC30A9
regulation of mitochondrion organization	1	842.6×	0.003	SLC30A9
intracellular zinc ion homeostasis	1	481.5×	0.003	SLC30A9
nucleotide-excision repair	1	383.0×	0.003	SLC30A9
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	SLC30A9

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
SLC30A9	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	SLC30A9

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)
SLC30A9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.