intellectual developmental disorder, X-linked, syndromic 37

Summary

intellectual developmental disorder, X-linked, syndromic 37 (MONDO:0958322) is a disease caused by ZFX (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ZFX (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, X-linked, syndromic 37
Mondo ID	MONDO:0958322
OMIM	301118
UMLS	C5935567
MedGen	1854940
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants · 2 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 › X-linked syndromic intellectual disability › intellectual developmental disorder, X-linked, syndromic 37

Related subtypes (80): X-linked intellectual disability-psychosis-macroorchidism syndrome, X-linked intellectual disability-plagiocephaly syndrome, intellectual disability, X-linked 49, MEHMO syndrome, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability, Stocco dos Santos type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, X-linked intellectual disability-cerebellar hypoplasia syndrome, Allan-Herndon-Dudley syndrome, syndromic X-linked intellectual disability Claes-Jensen type, X-linked intellectual disability-retinitis pigmentosa syndrome, syndromic X-linked intellectual disability 14, syndromic X-linked intellectual disability 94, intellectual disability, X-linked syndromic, Turner type, syndromic X-linked intellectual disability Shrimpton type, X-linked intellectual disability-craniofacioskeletal syndrome, syndromic X-linked intellectual disability Raymond type, syndromic X-linked intellectual disability 17, syndromic X-linked intellectual disability Nascimento type, syndromic X-linked intellectual disability Chudley-Schwartz type, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome, X-linked intellectual disability, Cantagrel type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked, syndromic, Bain type, Borjeson-Forssman-Lehmann syndrome, Coffin-Lowry syndrome, syndromic X-linked intellectual disability 5, X-linked intellectual disability-seizures-psoriasis syndrome, Renpenning syndrome, Partington syndrome, syndromic X-linked intellectual disability 12, severe X-linked intellectual disability, Gustavson type, syndromic X-linked intellectual disability Snyder type, Wilson-Turner syndrome, Prieto syndrome, skeletal dysplasia-intellectual disability syndrome, X-linked intellectual disability-spastic quadriparesis syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked intellectual disability, Schimke type, X-linked intellectual disability, Cilliers type, X-linked intellectual disability, van Esch type, X-linked intellectual disability-epilepsy syndrome, ATR-X-related syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, X-linked intellectual disability, Schutz type, X-linked intellectual disability-hypotonia-movement disorder syndrome, X-linked intellectual disability with isolated growth hormone deficiency, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-precocious puberty-obesity syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability-macrocephaly-macroorchidism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Seemanova type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, X-linked intellectual disability-acromegaly-hyperactivity syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, fried syndrome, X-linked intellectual disability-ataxia-apraxia syndrome, intellectual developmental disorder, X-linked, syndromic, Pilorge type, Paganini-Miozzo syndrome, intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type, intellectual disability, X-linked, syndromic, 35, intellectual disability, X-linked, syndromic, Houge type, MED12-related intellectual disability syndrome, NAA10-related syndrome, ATP6AP2-related disorder, X-linked intellectual disability with hypopituitarism, SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder, intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, CASK-related intellectual disability

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

12 retrieved; paginated sample, class counts are floors:

7 pathogenic, 3 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3066049	NM_003410.4(ZFX):c.2312C>T (p.Thr771Met)	ZFX	Pathogenic	criteria provided, single submitter
3066050	NM_003410.4(ZFX):c.2321A>G (p.Tyr774Cys)	ZFX	Pathogenic	criteria provided, multiple submitters, no conflicts
3066051	NM_003410.4(ZFX):c.2357G>A (p.Arg786Gln)	ZFX	Pathogenic	no assertion criteria provided
3066052	NM_003410.4(ZFX):c.1319dup (p.Leu440fs)	ZFX	Pathogenic	no assertion criteria provided
3066053	NM_003410.4(ZFX):c.115_116del (p.Val39fs)	ZFX	Pathogenic	no assertion criteria provided
3367188	NM_003410.4(ZFX):c.1996_1997del (p.Met666fs)	ZFX	Pathogenic	criteria provided, single submitter
4813719	NM_003410.4(ZFX):c.1763_1764del (p.Ser588fs)	ZFX	Pathogenic	criteria provided, single submitter
4070904	NM_003410.4(ZFX):c.2363C>G (p.Pro788Arg)	ZFX	Likely pathogenic	criteria provided, single submitter
4819279	NM_003410.4(ZFX):c.458T>G (p.Val153Gly)	ZFX	Likely pathogenic	criteria provided, single submitter
3377325	NM_003410.4(ZFX):c.649G>A (p.Asp217Asn)	ZFX	Uncertain significance	criteria provided, single submitter
3770241	NM_003410.4(ZFX):c.1606C>T (p.Arg536Cys)	ZFX	Uncertain significance	criteria provided, single submitter
4532184	NM_003410.4(ZFX):c.356C>T (p.Ala119Val)	ZFX	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
ZFX	Strong	X-linked	intellectual developmental disorder, X-linked, syndromic 37	2

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
ZFX	HGNC:12869	ENSG00000005889	P17010	Zinc finger X-chromosomal protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZFX	Zinc finger X-chromosomal protein	Probable transcriptional activator.

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)
ZFX	Transcription factor	no		Transcrp_activ_Zfx/Zfy-dom, Znf_C2H2_type, Znf_C2H2_sf

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
calcaneal tendon	1
germinal epithelium of ovary	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZFX	266	ubiquitous	marker	calcaneal tendon, sural nerve, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZFX	1,623

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZFX	P17010	54.07

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
positive regulation of transcription by RNA polymerase II	1	14.9×	0.086	ZFX
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ZFX

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ZFX	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ZFX

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ZFX	6	Binding:6

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	ZFX

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	1	ZFX
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.