Intellectual developmental disorder, autosomal recessive 69

Summary

Intellectual developmental disorder, autosomal recessive 69 (MONDO:0032715) is a disease caused by ZBTB11 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ZBTB11 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal recessive 69
Mondo ID	MONDO:0032715
OMIM	618383
Orphanet	699835
DOID	DOID:0081230
UMLS	C5193067
MedGen	1676539
GARD	0025727
Is cancer (heuristic)	no

Also known as: MRT69

Data availability: 19 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal recessive non-syndromic intellectual disability › intellectual developmental disorder, autosomal recessive 69

Related subtypes (67): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 3, intellectual disability, autosomal recessive 12, intellectual disability, autosomal recessive 5, intellectual disability, autosomal recessive 6, intellectual disability, autosomal recessive 7, intellectual disability, autosomal recessive 9, intellectual disability, autosomal recessive 10, intellectual disability, autosomal recessive 11, intellectual disability, autosomal recessive 4, intellectual disability, autosomal recessive 13, intellectual disability, autosomal recessive 14, Rafiq syndrome, intellectual disability, autosomal recessive 16, intellectual disability, autosomal recessive 18, intellectual disability, autosomal recessive 31, intellectual disability, autosomal recessive 29, intellectual disability, autosomal recessive 27, intellectual disability, autosomal recessive 33, intellectual disability, autosomal recessive 30, intellectual disability, autosomal recessive 19, intellectual disability, autosomal recessive 23, intellectual disability, autosomal recessive 24, intellectual disability, autosomal recessive 25, intellectual disability, autosomal recessive 28, intellectual disability, autosomal recessive 34, intellectual disability, autosomal recessive 42, intellectual disability, autosomal recessive 43, intellectual disability, autosomal recessive 44, intellectual disability, autosomal recessive 45, intellectual disability, autosomal recessive 46, intellectual disability, autosomal recessive 47, Al-Raqad syndrome, intellectual disability, autosomal recessive 50, intellectual disability, autosomal recessive 51, intellectual disability, autosomal recessive 52, intellectual disability, autosomal recessive 54, intellectual disability, autosomal recessive 56, intellectual developmental disorder, autosomal recessive 74, intellectual disability, autosomal recessive 57, intellectual disability, autosomal recessive 58, intellectual disability, autosomal recessive 59, pontocerebellar hypoplasia type 1, intellectual disability, autosomal recessive 64, intellectual disability, autosomal recessive 65, intellectual developmental disorder, autosomal recessive 73, intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, intellectual disability, autosomal recessive 61, intellectual developmental disorder, autosomal recessive 76, intellectual developmental disorder, autosomal recessive 77, intellectual disability, autosomal recessive 66, intellectual developmental disorder, autosomal recessive 67, intellectual developmental disorder, autosomal recessive 68, intellectual developmental disorder, autosomal recessive 70, intellectual developmental disorder, autosomal recessive 71, intellectual developmental disorder, autosomal recessive 72, glycosylphosphatidylinositol biosynthesis defect 16, intellectual disability, autosomal recessive 60, intellectual disability, autosomal recessive 63, adenosine kinase deficiency, intellectual developmental disorder, autosomal recessive 78, intellectual developmental disorder, autosomal recessive 79, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, intellectual developmental disorder, autosomal recessive 81, intellectual developmental disorder, autosomal recessive 82, intellectual developmental disorder, autosomal recessive 83

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:

11 pathogenic, 7 uncertain significance, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703741	NM_014415.4(ZBTB11):c.2668A>G (p.Thr890Ala)	ZBTB11	Pathogenic	no assertion criteria provided
1703742	NM_014415.4(ZBTB11):c.2734C>T (p.Arg912Trp)	ZBTB11	Pathogenic	no assertion criteria provided
1703743	NM_014415.4(ZBTB11):c.907A>T (p.Ile303Phe)	ZBTB11	Pathogenic	no assertion criteria provided
1703744	NM_014415.4(ZBTB11):c.2779C>T (p.Arg927Ter)	ZBTB11	Pathogenic	no assertion criteria provided
2506345	NM_014415.4(ZBTB11):c.85_97del (p.Val29fs)	ZBTB11	Pathogenic	criteria provided, single submitter
3339890	NM_014415.4(ZBTB11):c.1508dup (p.Tyr503Ter)	ZBTB11	Pathogenic	criteria provided, single submitter
3370365	NM_014415.4(ZBTB11):c.2708G>A (p.Arg903His)	ZBTB11	Pathogenic	no assertion criteria provided
3370366	NM_014415.4:c.2977_2978del	ZBTB11	Pathogenic	no assertion criteria provided
625185	NM_014415.4(ZBTB11):c.2185C>T (p.His729Tyr)	ZBTB11	Pathogenic	no assertion criteria provided
625186	NM_014415.4(ZBTB11):c.2640T>G (p.His880Gln)	ZBTB11	Pathogenic	no assertion criteria provided
1703745	NM_014415.4(ZBTB11):c.154C>T (p.Arg52Trp)	ZBTB11-AS1	Pathogenic	no assertion criteria provided
1027862	NM_014415.4(ZBTB11):c.1342A>C (p.Ser448Arg)	ZBTB11	Uncertain significance	criteria provided, single submitter
1027863	NM_014415.4(ZBTB11):c.709G>A (p.Glu237Lys)	ZBTB11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027864	NM_014415.4(ZBTB11):c.799C>T (p.Leu267Phe)	ZBTB11	Uncertain significance	criteria provided, single submitter
2438637	NM_014415.4(ZBTB11):c.1999C>T (p.Arg667Ter)	ZBTB11	Uncertain significance	criteria provided, single submitter
3065506	NM_014415.4(ZBTB11):c.1342A>G (p.Ser448Gly)	ZBTB11	Uncertain significance	criteria provided, single submitter
4081021	NM_014415.4(ZBTB11):c.3079C>T (p.Gln1027Ter)	ZBTB11	Uncertain significance	criteria provided, single submitter
4081022	NM_014415.4(ZBTB11):c.617_620del (p.Glu206fs)	ZBTB11	Uncertain significance	criteria provided, single submitter
1684248	NM_014415.4(ZBTB11):c.1624-4C>T	ZBTB11	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
ZBTB11	Strong	Autosomal recessive	intellectual developmental disorder, autosomal recessive 69	3

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZBTB11	HGNC:16740	ENSG00000066422	O95625	Zinc finger and BTB domain-containing protein 11	gencc,clinvar
ZBTB11-AS1	HGNC:48573	ENSG00000256628		ZBTB11 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZBTB11	Zinc finger and BTB domain-containing protein 11	May be involved in transcriptional regulation.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZBTB11	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
ZBTB11-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
secondary oocyte	1
sperm	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZBTB11	295	ubiquitous	yes	sperm, secondary oocyte, endothelial cell
ZBTB11-AS1	163	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZBTB11	1,776
ZBTB11-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZBTB11	O95625	62.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
regulation of DNA-templated transcription	1	31.6×	0.032	ZBTB11

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
ZBTB11	0	0
ZBTB11-AS1	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
ZBTB11	3	Binding:3

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	2	ZBTB11, ZBTB11-AS1

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)
ZBTB11	3	—
ZBTB11-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.