intellectual disability, Wolff type

Summary

intellectual disability, Wolff type (MONDO:0010203) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 29

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0000047	Hypospadias	Very frequent (80-99%)
HP:0000179	Thick lower lip vermilion	Very frequent (80-99%)
HP:0000308	Microretrognathia	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000400	Macrotia	Very frequent (80-99%)
HP:0000414	Bulbous nose	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000582	Upslanted palpebral fissure	Very frequent (80-99%)
HP:0001176	Large hands	Very frequent (80-99%)
HP:0001376	Limitation of joint mobility	Very frequent (80-99%)
HP:0002162	Low posterior hairline	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0009882	Short distal phalanx of finger	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0100490	Camptodactyly of finger	Very frequent (80-99%)
HP:0000023	Inguinal hernia	Frequent (30-79%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000202	Orofacial cleft	Frequent (30-79%)
HP:0000340	Sloping forehead	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001597	Abnormality of the nail	Frequent (30-79%)
HP:0002242	Abnormal intestine morphology	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0008559	Hypoplastic superior helix	Frequent (30-79%)
HP:0011304	Broad thumb	Frequent (30-79%)
HP:0100335	Non-midline cleft of the upper lip	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, Wolff type
Mondo ID	MONDO:0010203
MeSH	C537448
OMIM	277990
Orphanet	3080
UMLS	C1848439
MedGen	336345
GARD	0003530
Is cancer (heuristic)	no

Also known as: WOLFF mental retardation syndrome · Wolff-Zimmermann syndrome

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › intellectual disability, Wolff type

Related subtypes (16): Smith-Magenis syndrome, intellectual disability, Buenos-Aires type, CK syndrome, AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome, 7p22.1 microduplication syndrome, 9p13 microdeletion syndrome, 3q27.3 microdeletion syndrome, 9q31.1q31.3 microdeletion syndrome, Rubinstein-Taybi syndrome, X-linked syndromic intellectual disability, 9q33.3q34.11 microdeletion syndrome, autosomal recessive syndromic intellectual disability, autosomal dominant syndromic intellectual disability, aplasia cutis-enamel dysplasia syndrome, 2p25.3 microduplication syndrome, dyneinopathy

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/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
188930	NM_000053.4(ATP7B):c.813C>A (p.Cys271Ter)	ATP7B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP7B	Orphanet:905	Wilson disease

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
ATP7B	HGNC:870	ENSG00000123191	P35670	Copper-transporting ATPase 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP7B	Copper-transporting ATPase 2	Copper ion transmembrane transporter involved in the export of copper out of the cells.

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)
ATP7B	Transcription factor	no	7.2.2.8	P_typ_ATPase, HMA_dom, HMA_Cu_ion-bd

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
nasal cavity epithelium	1
nasal cavity mucosa	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP7B	205	ubiquitous	marker	nasal cavity epithelium, right testis, nasal cavity mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP7B	2,536

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP7B	P35670	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Ion transport by P-type ATPases	1	207.6×	0.014	ATP7B
Ion channel transport	1	96.0×	0.016	ATP7B
Transport of small molecules	1	25.1×	0.040	ATP7B

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
copper ion export	1	5617.3×	0.001	ATP7B
obsolete sequestering of calcium ion	1	3370.4×	0.001	ATP7B
viral translational frameshifting	1	2808.7×	0.001	ATP7B
copper ion import	1	2407.4×	0.001	ATP7B
copper ion transport	1	1685.2×	0.001	ATP7B
response to copper ion	1	1532.0×	0.001	ATP7B
xenobiotic detoxification by transmembrane export across the plasma membrane	1	1123.5×	0.002	ATP7B
intracellular copper ion homeostasis	1	936.2×	0.002	ATP7B
intracellular zinc ion homeostasis	1	481.5×	0.003	ATP7B
lactation	1	421.3×	0.003	ATP7B
monoatomic ion transmembrane transport	1	208.1×	0.006	ATP7B
protein maturation	1	163.6×	0.006	ATP7B
establishment of localization in cell	1	160.5×	0.006	ATP7B

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
ATP7B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP7B	7.2.2.8, 7.2.2.9	P-type Cu+ transporter, P-type Cu2+ 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	ATP7B

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)
ATP7B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.