Intellectual developmental disorder, autosomal dominant 64

Summary

Intellectual developmental disorder, autosomal dominant 64 (MONDO:0030934) is a disease caused by ZNF292 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ZNF292 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 127

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 64
Mondo ID	MONDO:0030934
OMIM	619188
DOID	DOID:0061037
UMLS	C5543067
MedGen	1784554
GARD	0016478
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, autosomal dominant 64 · mental retardation, autosomal dominant 64 · MRD64 · ZNF292-related neurodevelopmental disorder · ZNF292-related syndrome

Data availability: 127 ClinVar variants · 3 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 64

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 66, 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

127 retrieved; paginated sample, class counts are floors:

66 uncertain significance, 26 likely pathogenic, 17 pathogenic, 7 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 3 likely benign, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1801324	NM_001281747.2(MLIP):c.2530C>T (p.Arg844Ter)	MLIP	Pathogenic	criteria provided, single submitter
1334883	NM_015021.3(ZNF292):c.6145dup (p.Ser2049fs)	ZNF292	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1698954	NM_015021.3(ZNF292):c.6266_6269del (p.Lys2089fs)	ZNF292	Pathogenic	criteria provided, single submitter
1711978	NM_015021.3(ZNF292):c.6823C>T (p.Arg2275Ter)	ZNF292	Pathogenic	criteria provided, multiple submitters, no conflicts
1803333	NM_015021.3(ZNF292):c.3432_3436del (p.Asn1144fs)	ZNF292	Pathogenic	criteria provided, multiple submitters, no conflicts
1805350	NM_015021.3(ZNF292):c.4450C>T (p.Gln1484Ter)	ZNF292	Pathogenic	criteria provided, single submitter
2627676	NM_015021.3(ZNF292):c.1414G>T (p.Glu472Ter)	ZNF292	Pathogenic	criteria provided, single submitter
3068522	NM_015021.3(ZNF292):c.5233C>T (p.Gln1745Ter)	ZNF292	Pathogenic	criteria provided, single submitter
3194984	NM_015021.3(ZNF292):c.5950_5956del (p.Ile1984fs)	ZNF292	Pathogenic	criteria provided, multiple submitters, no conflicts
3255095	NM_015021.3(ZNF292):c.1717del (p.Ile573fs)	ZNF292	Pathogenic	criteria provided, single submitter
3376205	NM_015021.3(ZNF292):c.3915dup (p.Asn1306Ter)	ZNF292	Pathogenic	criteria provided, single submitter
3377128	NM_015021.3(ZNF292):c.6239_6240del (p.Arg2080fs)	ZNF292	Pathogenic	criteria provided, single submitter
3897571	NM_015021.3(ZNF292):c.4789C>T (p.Gln1597Ter)	ZNF292	Pathogenic	criteria provided, single submitter
4086075	NM_015021.3(ZNF292):c.4098G>A (p.Trp1366Ter)	ZNF292	Pathogenic	criteria provided, single submitter
431106	NM_015021.3(ZNF292):c.3066_3069del (p.Glu1022fs)	ZNF292	Pathogenic	criteria provided, multiple submitters, no conflicts
4687979	NM_015021.3(ZNF292):c.2966_2967del (p.Arg989fs)	ZNF292	Pathogenic	criteria provided, single submitter
981386	NM_015021.3(ZNF292):c.265C>T (p.Arg89Ter)	ZNF292	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
981392	NM_015021.3(ZNF292):c.6160_6161del (p.Glu2054fs)	ZNF292	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
982158	NM_015021.3(ZNF292):c.2490_2494dup (p.Ser832fs)	ZNF292	Pathogenic/Likely pathogenic	no assertion criteria provided
982160	NM_015021.3(ZNF292):c.3460_3463del (p.Val1154fs)	ZNF292	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
982162	NM_015021.3(ZNF292):c.3724del (p.Gln1242fs)	ZNF292	Pathogenic	criteria provided, single submitter
982164	NM_015021.3(ZNF292):c.4417dup (p.Ser1473fs)	ZNF292	Pathogenic/Likely pathogenic	no assertion criteria provided
982198	NM_015021.3(ZNF292):c.6279dup (p.Arg2094fs)	ZNF292	Pathogenic	criteria provided, multiple submitters, no conflicts
982202	NM_015021.3(ZNF292):c.1897C>T (p.Arg633Ter)	ZNF292	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2576539	NM_015021.3(ZNF292):c.61G>C (p.Glu21Gln)	LOC129996783	Likely pathogenic	criteria provided, single submitter
1172644	NM_015021.3(ZNF292):c.3319C>T (p.Arg1107Ter)	ZNF292	Likely pathogenic	criteria provided, single submitter
1320141	NM_015021.3(ZNF292):c.6015dup (p.Lys2006fs)	ZNF292	Likely pathogenic	criteria provided, single submitter
1320246	NM_015021.3(ZNF292):c.3862dup (p.Ser1288fs)	ZNF292	Likely pathogenic	criteria provided, single submitter
1331344	NM_015021.3(ZNF292):c.4862del (p.Asn1621fs)	ZNF292	Likely pathogenic	no assertion criteria provided
1333302	NM_015021.3(ZNF292):c.5906_5909del (p.Gln1969fs)	ZNF292	Likely pathogenic	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
ZNF292	Strong	Autosomal dominant	intellectual developmental disorder, autosomal dominant 64	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZNF292	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZNF292	HGNC:18410	ENSG00000188994	O60281	Zinc finger protein 292	gencc,clinvar
MLIP	HGNC:21355	ENSG00000146147	Q5VWP3	Muscular LMNA-interacting protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZNF292	Zinc finger protein 292	May be involved in transcriptional regulation.
MLIP	Muscular LMNA-interacting protein	Required for myoblast differentiation into myotubes, possibly acting as a transcriptional regulator of the myogenic program.

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)
ZNF292	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GH-ZnFinger_Regulators
MLIP	Other/Unknown	no		MLIP

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
caput epididymis	1
cauda epididymis	1
cardiac muscle of right atrium	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZNF292	293	ubiquitous	marker	caput epididymis, calcaneal tendon, cauda epididymis
MLIP	186	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZNF292	1,657
MLIP	16

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ZNF292	O60281	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MLIP	Q5VWP3	43.75

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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cardiac muscle hypertrophy in response to stress	1	936.2×	0.005	MLIP
negative regulation of cardiac muscle hypertrophy	1	561.7×	0.005	MLIP
transcription by RNA polymerase II	1	35.3×	0.056	MLIP
negative regulation of transcription by RNA polymerase II	1	8.9×	0.156	MLIP
positive regulation of transcription by RNA polymerase II	1	7.4×	0.156	MLIP
regulation of transcription by RNA polymerase II	1	5.8×	0.164	ZNF292

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
ZNF292	0	0
MLIP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	ZNF292, MLIP

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)
ZNF292	0	—
MLIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.