HAND2 related congenital heart defect

Summary

HAND2 related congenital heart defect (MONDO:0800476) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	HAND2 related congenital heart defect
Mondo ID	MONDO:0800476
Is cancer (heuristic)	no

Also known as: bHLHa26 · DHAND · DHAND2 · HAND2 related congenital heart defect · HAND2-related congenital heart defect · Hed · HLH transcription factor HAND2 · Thing2

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › HAND2 related congenital heart defect

Related subtypes (22): congenital heart defects, multiple types, heart septal defect, tetralogy of fallot, heart defects-limb shortening syndrome, tricuspid atresia, patent ductus arteriosus, coronary artery congenital malformation, mitral atresia disorder, persistent truncus arteriosus, dextro-looped transposition of the great arteries, aortic valve atresia, congenital pulmonary veins anomaly, mehta lewis patton syndrome, structural congenital heart disease, multiple types - GATA4, GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes, GATA5-related congenital heart defects, RBFOX2-related congenital heart disorder, syndromic congenital heart disease, ACTC1-related distal arthrogryposis with congenital heart disease, HAND1 related congenital heart defect, TFAP2B-related congenital heart disease spectrum disorder, PLD1-related congenital heart disease

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
HAND2	Moderate	Autosomal dominant	HAND2 related congenital heart defect	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HAND2	Orphanet:154	Familial isolated dilated cardiomyopathy

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
HAND2	HGNC:4808	ENSG00000164107	P61296	Heart- and neural crest derivatives-expressed protein 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HAND2	Heart- and neural crest derivatives-expressed protein 2	Essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

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)
HAND2	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators

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
apex of heart	1
lower esophagus muscularis layer	1
muscle layer of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HAND2	147	broad	marker	muscle layer of sigmoid colon, apex of heart, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HAND2	1,828

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HAND2	P61296	67.30

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
Cardiogenesis	1	423.0×	0.004	HAND2
Transcriptional regulation by RUNX2	1	253.8×	0.004	HAND2

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 semaphorin-plexin signaling pathway	1	16852.0×	0.001	HAND2
visceral serous pericardium development	1	8426.0×	0.001	HAND2
cell proliferation involved in outflow tract morphogenesis	1	8426.0×	0.001	HAND2
primary palate development	1	8426.0×	0.001	HAND2
apoptotic process involved in heart morphogenesis	1	5617.3×	0.001	HAND2
cardiac neural crest cell development involved in outflow tract morphogenesis	1	5617.3×	0.001	HAND2
cardiac right ventricle formation	1	4213.0×	0.001	HAND2
regulation of secondary heart field cardioblast proliferation	1	4213.0×	0.001	HAND2
cartilage morphogenesis	1	3370.4×	0.001	HAND2
cardiac neural crest cell migration involved in outflow tract morphogenesis	1	2407.4×	0.001	HAND2
noradrenergic neuron differentiation	1	2407.4×	0.001	HAND2
regulation of tissue remodeling	1	2106.5×	0.001	HAND2
norepinephrine biosynthetic process	1	2106.5×	0.001	HAND2
tongue development	1	2106.5×	0.001	HAND2
coronary artery morphogenesis	1	1872.4×	0.001	HAND2
suckling behavior	1	1685.2×	0.002	HAND2
peripheral nervous system neuron development	1	1532.0×	0.002	HAND2
adult heart development	1	1203.7×	0.002	HAND2
negative regulation of epithelial cell apoptotic process	1	1203.7×	0.002	HAND2
mesenchymal cell proliferation	1	1123.5×	0.002	HAND2
sympathetic nervous system development	1	936.2×	0.002	HAND2
epithelial cell apoptotic process	1	842.6×	0.002	HAND2
positive regulation of cardiac muscle hypertrophy	1	732.7×	0.002	HAND2
positive regulation of p38MAPK cascade	1	624.1×	0.003	HAND2
negative regulation of cardiac muscle cell apoptotic process	1	543.6×	0.003	HAND2
embryonic skeletal system development	1	391.9×	0.004	HAND2
thymus development	1	337.0×	0.005	HAND2
outflow tract morphogenesis	1	306.4×	0.005	HAND2
odontogenesis of dentin-containing tooth	1	300.9×	0.005	HAND2
embryonic digit morphogenesis	1	300.9×	0.005	HAND2

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
HAND2	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	HAND2

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)
HAND2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.