Intellectual developmental disorder with neuropsychiatric features

Summary

Intellectual developmental disorder with neuropsychiatric features (MONDO:0044322) is a disease caused by SLC45A1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC45A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with neuropsychiatric features
Mondo ID	MONDO:0044322
OMIM	617532
UMLS	C4479636
MedGen	1379216
Is cancer (heuristic)	no

Also known as: IDDNPF · intellectual developmental disorder with neuropsychiatric features

Data availability: 25 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › autosomal recessive syndromic intellectual disability › intellectual developmental disorder with neuropsychiatric features

Related subtypes (6): Cohen syndrome, intellectual disability-hypotonia-spasticity-sleep disorder syndrome, intellectual disability, autosomal recessive 53, short stature-brachydactyly-obesity-global developmental delay syndrome, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, Al Kaissi 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

25 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 5 benign, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
428598	NM_001080397.3(SLC45A1):c.629C>T (p.Ala210Val)	SLC45A1	Likely pathogenic	criteria provided, single submitter
428599	NM_001080397.3(SLC45A1):c.526C>T (p.Arg176Trp)	SLC45A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029016	NM_001080397.3(SLC45A1):c.110G>T (p.Arg37Leu)	SLC45A1	Uncertain significance	criteria provided, single submitter
1029017	NM_001080397.3(SLC45A1):c.1256T>A (p.Leu419Gln)	SLC45A1	Uncertain significance	criteria provided, single submitter
1029018	NM_001080397.3(SLC45A1):c.1582G>A (p.Val528Ile)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029020	NM_001080397.3(SLC45A1):c.1954C>T (p.Leu652Phe)	SLC45A1	Uncertain significance	criteria provided, single submitter
1029021	NM_001080397.3(SLC45A1):c.742G>C (p.Val248Leu)	SLC45A1	Uncertain significance	criteria provided, single submitter
1029022	NM_001080397.3(SLC45A1):c.938C>G (p.Ser313Cys)	SLC45A1	Uncertain significance	criteria provided, single submitter
1033649	NM_001080397.3(SLC45A1):c.814T>C (p.Phe272Leu)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033650	NM_001080397.3(SLC45A1):c.935C>T (p.Pro312Leu)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1325499	NM_001080397.3(SLC45A1):c.2009G>A (p.Arg670Gln)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1700243	NM_001080397.3(SLC45A1):c.114C>A (p.His38Gln)	SLC45A1	Uncertain significance	criteria provided, single submitter
2342682	NM_001080397.3(SLC45A1):c.86C>T (p.Thr29Met)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3164866	NM_001080397.3(SLC45A1):c.124C>T (p.Arg42Trp)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3236658	NM_001080397.3(SLC45A1):c.1256T>C (p.Leu419Pro)	SLC45A1	Uncertain significance	criteria provided, single submitter
3242175	NM_001080397.3(SLC45A1):c.170G>A (p.Arg57His)	SLC45A1	Uncertain significance	criteria provided, single submitter
3376222	NM_001080397.3(SLC45A1):c.1237C>T (p.Arg413Cys)	SLC45A1	Uncertain significance	criteria provided, single submitter
3587989	NM_001080397.3(SLC45A1):c.1468G>A (p.Val490Met)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4278206	NM_001080397.3(SLC45A1):c.167T>C (p.Ile56Thr)	SLC45A1	Uncertain significance	criteria provided, single submitter
983315	NM_001080397.3(SLC45A1):c.1178G>A (p.Gly393Asp)	SLC45A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1282969	NM_001080397.3(SLC45A1):c.*20C>T	SLC45A1	Benign	criteria provided, multiple submitters, no conflicts
1302025	NM_001080397.3(SLC45A1):c.942A>G (p.Pro314=)	SLC45A1	Benign	criteria provided, multiple submitters, no conflicts
1333146	NM_001080397.3(SLC45A1):c.831G>C (p.Leu277=)	SLC45A1	Benign	criteria provided, multiple submitters, no conflicts
1333148	NM_001080397.3(SLC45A1):c.1507G>T (p.Ala503Ser)	SLC45A1	Benign	criteria provided, multiple submitters, no conflicts
2585663	NM_001080397.3(SLC45A1):c.1335G>A (p.Pro445=)	SLC45A1	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SLC45A1	Strong	Autosomal recessive	intellectual developmental disorder with neuropsychiatric features	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC45A1	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
SLC45A1	HGNC:17939	ENSG00000162426	Q9Y2W3	Proton-associated sugar transporter A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC45A1	Proton-associated sugar transporter A	Proton-associated glucose transporter in the brain.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC45A1	Transporter	yes		MFS, MFS_trans_sf

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
prefrontal cortex	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC45A1	167	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC45A1	1,487

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC45A1	Q9Y2W3	66.26

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
galactose transmembrane transport	1	3370.4×	6e-04	SLC45A1
D-glucose transmembrane transport	1	936.2×	0.001	SLC45A1

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
SLC45A1	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	1	SLC45A1
E	Difficult family or no structure, no drug	0

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)
SLC45A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.