Atrial septal defect 3

Summary

Atrial septal defect 3 (MONDO:0013567) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 278

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial septal defect 3
Mondo ID	MONDO:0013567
MeSH	C563540
OMIM	614089
DOID	DOID:0110108
UMLS	C3279790
MedGen	481420
GARD	0015755
Is cancer (heuristic)	no

Also known as: ASD3 · atrial heart septal defect caused by mutation in MYH6 · atrial heart septal defect type 3 · atrial septal defect 3 · atrial septal defect type 3 · MYH6 atrial heart septal defect

Data availability: 278 ClinVar variants · 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 › heart septal defect › atrial septal defect › atrial septal defect 3

Related subtypes (14): Lutembacher syndrome, atrial septal defect 1, atrial septal defect 7, atrial septal defect 2, atrial septal defect 4, atrial septal defect 5, atrial septal defect 6, atrial septal defect 8, atrial septal defect 9, atrial septal defect, ostium secundum type, atrial septal defect, coronary sinus type, atrial septal defect, sinus venosus type, atrial septal defect, ostium primum type, patent foramen ovale

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

278 retrieved; paginated sample, class counts are floors:

205 uncertain significance, 29 conflicting classifications of pathogenicity, 19 benign/likely benign, 18 likely benign, 5 benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14148	NM_002471.4(MYH6):c.2459T>A (p.Ile820Asn)	MYH6	Pathogenic	no assertion criteria provided
3366965	NM_002471.4(MYH6):c.5164-2A>G	MYH6	Likely pathogenic	criteria provided, single submitter
1447754	NM_002471.4(MYH6):c.616AAG[1] (p.Lys207del)	LOC114827851	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191724	NM_002471.4(MYH6):c.115G>A (p.Val39Met)	LOC114827851	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44474	NM_002471.4(MYH6):c.292G>A (p.Glu98Lys)	LOC114827851	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
407143	NM_002471.4(MYH6):c.4991G>A (p.Arg1664His)	LOC126861896	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
537962	NM_002471.4(MYH6):c.4666G>A (p.Glu1556Lys)	LOC126861896	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032059	NM_002471.4(MYH6):c.1411-12T>C	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1284635	NM_002471.4(MYH6):c.2717G>A (p.Arg906His)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1432256	NM_002471.4(MYH6):c.409G>A (p.Glu137Lys)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
164230	NM_002471.4(MYH6):c.3508G>A (p.Glu1170Lys)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179023	NM_002471.4(MYH6):c.3220G>A (p.Asp1074Asn)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180424	NM_002471.4(MYH6):c.3893C>T (p.Ala1298Val)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191717	NM_002471.4(MYH6):c.3346C>A (p.Arg1116Ser)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191718	NM_002471.4(MYH6):c.2575G>T (p.Gly859Trp)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
228886	NM_002471.4(MYH6):c.1336G>A (p.Ala446Thr)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
239163	NM_002471.4(MYH6):c.1244G>C (p.Gly415Ala)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
264214	NM_002471.4(MYH6):c.5519A>G (p.Lys1840Arg)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
264374	NM_002471.4(MYH6):c.3612G>C (p.Glu1204Asp)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312860	NM_002471.4(MYH6):c.3604G>A (p.Val1202Met)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312866	NM_002471.4(MYH6):c.3164G>A (p.Arg1055Gln)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
373555	NM_002471.4(MYH6):c.5077G>A (p.Val1693Met)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
407141	NM_002471.4(MYH6):c.3230A>T (p.Gln1077Leu)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44513	NM_002471.4(MYH6):c.4505G>A (p.Arg1502Gln)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44533	NM_002471.4(MYH6):c.5293G>A (p.Ala1765Thr)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
520324	NM_002471.4(MYH6):c.2929-3C>T	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
565499	NM_002471.4(MYH6):c.3618C>T (p.Gly1206=)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
656980	NM_002471.4(MYH6):c.2189T>C (p.Val730Ala)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
691732	NM_002471.4(MYH6):c.3979-2A>C	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
800244	NM_002471.4(MYH6):c.1486G>A (p.Val496Met)	MYH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
MYH6	Strong	Autosomal dominant	atrial septal defect	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYH6	Orphanet:154	Familial isolated dilated cardiomyopathy
MYH6	Orphanet:166282	Hereditary sick sinus syndrome
MYH6	Orphanet:99103	Atrial septal defect, ostium secundum type

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
MYH6	HGNC:7576	ENSG00000197616	P13533	Myosin-6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYH6	Myosin-6	Muscle contraction.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYH6	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac atrium	1
cardiac muscle of right atrium	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYH6	154	tissue_specific	yes	cardiac muscle of right atrium, cardiac atrium, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH6	3,119

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYH6	P13533	74.91

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
Striated Muscle Contraction	1	308.6×	0.006	MYH6
Muscle contraction	1	77.2×	0.013	MYH6

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
visceral muscle development	1	16852.0×	0.001	MYH6
regulation of heart growth	1	8426.0×	0.001	MYH6
atrial cardiac muscle tissue morphogenesis	1	2407.4×	0.002	MYH6
adult heart development	1	1203.7×	0.002	MYH6
myofibril assembly	1	1123.5×	0.002	MYH6
cardiac muscle hypertrophy in response to stress	1	1053.2×	0.002	MYH6
muscle filament sliding	1	1053.2×	0.002	MYH6
regulation of the force of heart contraction	1	991.3×	0.002	MYH6
striated muscle contraction	1	842.6×	0.003	MYH6
ventricular cardiac muscle tissue morphogenesis	1	702.2×	0.003	MYH6
cardiac muscle cell development	1	624.1×	0.003	MYH6
regulation of heart contraction	1	495.6×	0.003	MYH6
regulation of heart rate	1	468.1×	0.003	MYH6
ATP metabolic process	1	468.1×	0.003	MYH6
cardiac muscle contraction	1	401.2×	0.003	MYH6
sarcomere organization	1	383.0×	0.003	MYH6
regulation of blood pressure	1	221.7×	0.005	MYH6
muscle contraction	1	208.1×	0.005	MYH6
in utero embryonic development	1	72.0×	0.014	MYH6

Therapeutics

Drug target analysis

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

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
MYH6	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	MYH6

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)
MYH6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.