congenital heart defects, multiple types, 1, X-linked

Summary

congenital heart defects, multiple types, 1, X-linked (MONDO:0800321) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital heart defects, multiple types, 1, X-linked
Mondo ID	MONDO:0800321
UMLS	C3151867
MedGen	463217
GARD	0026500
Is cancer (heuristic)	no

Also known as: CHTD1

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › congenital anomaly of cardiovascular system › congenital heart malformation › congenital heart defects, multiple types, 1, X-linked

Related subtypes (25): transposition of the great arteries, congenital left-sided heart lesions, interventricular septum aneurysm, congenital heart defects, multiple types, 2, coronary artery congenital malformation, criss-cross heart, triatrial heart, familial idiopathic dilatation of the right atrium, cardiac diverticulum, conotruncal heart malformations, congenital mitral malformation, congenital pericardium anomaly, ectopia cordis, visceral heterotaxy, mesocardia, univentricular cardiopathy, congenital anomaly of the great arteries, Laubry-Pezzi syndrome, congenital Gerbode defect, juxtaposition of the atrial appendages, ectasia of the right atrial appendage, ectasia of the left appendage, atrial septal aneurysm, congenital acardia, congenital right-sided heart lesions

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11435	NM_003413.4(ZIC3):c.1222A>T (p.Lys408Ter)	ZIC3	Pathogenic	no assertion criteria provided
11439	NM_003413.4(ZIC3):c.649C>G (p.Pro217Ala)	ZIC3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZIC3	Orphanet:157769	Situs ambiguus
ZIC3	Orphanet:216718	Isolated congenitally uncorrected transposition of the great arteries

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
ZIC3	HGNC:12874	ENSG00000156925	O60481	Zinc finger protein ZIC 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZIC3	Zinc finger protein ZIC 3	Acts as a 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)
ZIC3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Znf_ZIC

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZIC3	81	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZIC3	1,600

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ZIC3	O60481	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation	1	878.5×	0.002	ZIC3
Transcriptional regulation of pluripotent stem cells	1	543.8×	0.002	ZIC3

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
central nervous system segmentation	1	16852.0×	0.001	ZIC3
neural plate development	1	8426.0×	0.001	ZIC3
determination of left/right asymmetry in nervous system	1	8426.0×	0.001	ZIC3
atrial cardiac muscle tissue development	1	4213.0×	0.001	ZIC3
determination of pancreatic left/right asymmetry	1	3370.4×	0.001	ZIC3
axial mesoderm development	1	3370.4×	0.001	ZIC3
germ-line stem cell population maintenance	1	2808.7×	0.001	ZIC3
determination of digestive tract left/right asymmetry	1	2808.7×	0.001	ZIC3
determination of liver left/right asymmetry	1	2808.7×	0.001	ZIC3
paraxial mesoderm development	1	1685.2×	0.002	ZIC3
outer ear morphogenesis	1	1532.0×	0.002	ZIC3
primitive streak formation	1	1404.3×	0.002	ZIC3
left/right axis specification	1	1203.7×	0.002	ZIC3
limb morphogenesis	1	1053.2×	0.002	ZIC3
cranial skeletal system development	1	936.2×	0.002	ZIC3
face development	1	802.5×	0.002	ZIC3
olfactory bulb development	1	766.0×	0.002	ZIC3
embryonic pattern specification	1	543.6×	0.003	ZIC3
mRNA transcription by RNA polymerase II	1	330.4×	0.005	ZIC3
stem cell differentiation	1	300.9×	0.005	ZIC3
heart looping	1	267.5×	0.005	ZIC3
determination of left/right symmetry	1	255.3×	0.005	ZIC3
hippocampus development	1	230.8×	0.006	ZIC3
lung development	1	198.3×	0.006	ZIC3
smoothened signaling pathway	1	181.2×	0.007	ZIC3
skeletal system development	1	125.8×	0.009	ZIC3
central nervous system development	1	115.4×	0.010	ZIC3
neuron differentiation	1	100.3×	0.011	ZIC3
positive regulation of DNA-templated transcription	1	27.9×	0.037	ZIC3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	ZIC3

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
ZIC3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	ZIC3

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)
ZIC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.