Intellectual developmental disorder, autosomal dominant 66

Summary

Intellectual developmental disorder, autosomal dominant 66 (MONDO:0030891) is a disease caused by ATP2B1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP2B1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 45

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 66
Mondo ID	MONDO:0030891
OMIM	619910
DOID	DOID:0061039
UMLS	C5677000
MedGen	1812470
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, autosomal dominant 66 · mental retardation, autosomal dominant 66 · MRD66

Data availability: 45 ClinVar variants · 5 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 dominant disease › intellectual disability, autosomal dominant › intellectual developmental disorder, autosomal dominant 66

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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

45 retrieved; paginated sample, class counts are floors:

25 uncertain significance, 13 likely pathogenic, 4 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1679165	NM_001366521.1(ATP2B1):c.2632C>T (p.Gln878Ter)	ATP2B1	Pathogenic	criteria provided, single submitter
3377230	NM_001366521.1(ATP2B1):c.2954del (p.Phe985fs)	ATP2B1	Pathogenic	criteria provided, single submitter
3768438	NM_001366521.1(ATP2B1):c.2443-2A>G	ATP2B1	Pathogenic	criteria provided, single submitter
4082342	NM_001366521.1(ATP2B1):c.1339_1342del (p.Val447fs)	ATP2B1	Pathogenic	criteria provided, single submitter
1679159	NM_001366521.1(ATP2B1):c.716A>G (p.Asp239Gly)	ATP2B1	Likely pathogenic	criteria provided, single submitter
1679160	NM_001366521.1(ATP2B1):c.791C>T (p.Thr264Ile)	ATP2B1	Likely pathogenic	criteria provided, single submitter
1679161	NM_001366521.1(ATP2B1):c.1274C>A (p.Thr425Lys)	ATP2B1	Likely pathogenic	criteria provided, single submitter
1679166	NM_001366521.1(ATP2B1):c.458G>A (p.Trp153Ter)	ATP2B1	Likely pathogenic	criteria provided, single submitter
1684514	NM_001366521.1(ATP2B1):c.1907_1908del (p.Val636fs)	ATP2B1	Likely pathogenic	criteria provided, single submitter
2626973	NM_001366521.1(ATP2B1):c.406+1G>A	ATP2B1	Likely pathogenic	criteria provided, single submitter
2683828	NM_001366521.1(ATP2B1):c.2509_2512del (p.Ser837fs)	ATP2B1	Likely pathogenic	criteria provided, single submitter
3376912	NM_001366521.1(ATP2B1):c.1130-2A>C	ATP2B1	Likely pathogenic	criteria provided, single submitter
3377235	NM_001366521.1(ATP2B1):c.3215C>T (p.Ala1072Val)	ATP2B1	Likely pathogenic	criteria provided, single submitter
3766578	NM_001366521.1(ATP2B1):c.2677del (p.Leu892_Ile893insTer)	ATP2B1	Likely pathogenic	criteria provided, single submitter
4293494	NM_001366521.1(ATP2B1):c.2855del (p.Lys952fs)	ATP2B1	Likely pathogenic	criteria provided, single submitter
4796793	NM_001366521.1(ATP2B1):c.2750del (p.Tyr917fs)	ATP2B1	Likely pathogenic	criteria provided, single submitter
982810	NM_001366521.1(ATP2B1):c.1376A>G (p.His459Arg)	ATP2B1	Likely pathogenic	criteria provided, single submitter
1679162	NM_001366521.1(ATP2B1):c.2365C>T (p.Arg789Cys)	ATP2B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679164	NM_001366521.1(ATP2B1):c.2972G>A (p.Arg991Gln)	ATP2B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1697311	NM_001366521.1(ATP2B1):c.1235A>G (p.Tyr412Cys)	ATP2B1	Uncertain significance	criteria provided, single submitter
1710505	NM_001366521.1(ATP2B1):c.3632G>T (p.Ser1211Ile)	ATP2B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1712324	NM_001366521.1(ATP2B1):c.2426A>G (p.Asp809Gly)	ATP2B1	Uncertain significance	criteria provided, single submitter
1801725	NM_001366521.1(ATP2B1):c.2359G>T (p.Asp787Tyr)	ATP2B1	Uncertain significance	no assertion criteria provided
2444387	NM_001366521.1(ATP2B1):c.3367G>T (p.Ala1123Ser)	ATP2B1	Uncertain significance	criteria provided, single submitter
2582467	NM_001366521.1(ATP2B1):c.1550G>C (p.Gly517Ala)	ATP2B1	Uncertain significance	criteria provided, single submitter
2688644	NM_001366521.1(ATP2B1):c.758C>G (p.Ser253Cys)	ATP2B1	Uncertain significance	criteria provided, single submitter
3233326	NM_001366521.1(ATP2B1):c.1816A>G (p.Ile606Val)	ATP2B1	Uncertain significance	criteria provided, single submitter
3256693	NM_001366521.1(ATP2B1):c.1157T>C (p.Ile386Thr)	ATP2B1	Uncertain significance	criteria provided, single submitter
3342278	NM_001366521.1(ATP2B1):c.2682G>A (p.Met894Ile)	ATP2B1	Uncertain significance	criteria provided, single submitter
3360687	NM_001366521.1(ATP2B1):c.2995G>A (p.Val999Ile)	ATP2B1	Uncertain significance	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
ATP2B1	Strong	Autosomal dominant	intellectual developmental disorder, autosomal dominant 66	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP2B1	Orphanet:528084	Non-specific 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
ATP2B1	HGNC:814	ENSG00000070961	P20020	Plasma membrane calcium-transporting ATPase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP2B1	Plasma membrane calcium-transporting ATPase 1	Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP2B1	Transcription factor	no	7.2.2.10	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, ATPase_P-typ_cation-transptr_C

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
Brodmann (1909) area 23	1
frontal pole	1
lateral nuclear group of thalamus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP2B1	296	ubiquitous	marker	frontal pole, Brodmann (1909) area 23, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP2B1	3,055

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP2B1	P20020	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Reduction of cytosolic Ca++ levels	1	951.7×	0.009	ATP2B1
Platelet calcium homeostasis	1	713.8×	0.009	ATP2B1
Sensory processing of sound	1	308.6×	0.011	ATP2B1
Platelet homeostasis	1	278.5×	0.011	ATP2B1
Ion transport by P-type ATPases	1	207.6×	0.011	ATP2B1
Ion homeostasis	1	203.9×	0.011	ATP2B1
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.011	ATP2B1
Cardiac conduction	1	108.8×	0.014	ATP2B1
Ion channel transport	1	96.0×	0.014	ATP2B1
Sensory Perception	1	95.2×	0.014	ATP2B1
Muscle contraction	1	77.2×	0.015	ATP2B1
Hemostasis	1	36.0×	0.030	ATP2B1
Transport of small molecules	1	25.1×	0.040	ATP2B1

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
regulation of vascular associated smooth muscle contraction	1	3370.4×	0.002	ATP2B1
calcium ion export across plasma membrane	1	2808.7×	0.002	ATP2B1
regulation of cellular response to insulin stimulus	1	1532.0×	0.002	ATP2B1
negative regulation of cytosolic calcium ion concentration	1	1296.3×	0.002	ATP2B1
regulation of cardiac conduction	1	842.6×	0.003	ATP2B1
positive regulation of calcium ion transport	1	581.1×	0.003	ATP2B1
negative regulation of cytokine production	1	510.7×	0.003	ATP2B1
positive regulation of bone mineralization	1	391.9×	0.003	ATP2B1
regulation of cytosolic calcium ion concentration	1	383.0×	0.003	ATP2B1
regulation of blood pressure	1	221.7×	0.005	ATP2B1
monoatomic ion transmembrane transport	1	208.1×	0.005	ATP2B1

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
ATP2B1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP2B1	7.2.2.10	P-type Ca2+ transporter

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	ATP2B1

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)
ATP2B1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.