Heterotaxy, visceral, 2, autosomal

Summary

Heterotaxy, visceral, 2, autosomal (MONDO:0011546) is a disease caused by CFC1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CFC1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	heterotaxy, visceral, 2, autosomal
Mondo ID	MONDO:0011546
OMIM	605376
DOID	DOID:0051017
UMLS	C1415817
MedGen	237904
GARD	0024805
Is cancer (heuristic)	no

Also known as: DTGA2 · heterotaxy, visceral, 2, autosomal · HTX2 · transposition of the great arteries, dextro-looped 2

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › congenital anomaly of cardiovascular system › congenital heart malformation › transposition of the great arteries › heterotaxy, visceral, 2, autosomal

Related subtypes (2): congenitally corrected transposition of the great arteries, dextro-looped transposition of the great arteries

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

10 retrieved; paginated sample, class counts are floors:

3 not provided, 2 benign, 2 pathogenic, 1 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
5187	NM_032545.4(CFC1):c.334C>T (p.Arg112Cys)	CFC1	Pathogenic	no assertion criteria provided
5190	NM_032545.4(CFC1):c.361_362+18dup	CFC1	Pathogenic	no assertion criteria provided
4294348	NM_032545.4(CFC1):c.195dup (p.Glu66fs)	CFC1	Likely pathogenic	criteria provided, single submitter
5188	NM_032545.4(CFC1):c.522del (p.Ala175fs)	CFC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779059	NM_032545.4(CFC1):c.83G>A (p.Arg28Lys)	CFC1	Uncertain significance	criteria provided, single submitter
136735	NM_032545.4(CFC1):c.433G>A (p.Ala145Thr)	CFC1	Benign	criteria provided, multiple submitters, no conflicts
801752	NM_032545.4(CFC1):c.484T>C (p.Phe162Leu)	CFC1	Benign	criteria provided, single submitter
3764534	NM_032545.4(CFC1):c.183_184insGG (p.Thr62fs)	CFC1	not provided	no classification provided
3764535	NM_032545.4(CFC1):c.181_182insGC (p.Val61fs)	CFC1	not provided	no classification provided
3764536	NM_032545.4(CFC1):c.178_179insCGCCG (p.Glu60fs)	CFC1	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 5 · 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
CFC1	Strong	Autosomal dominant	heterotaxy, visceral, 2, autosomal	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFC1	Orphanet:157769	Situs ambiguus
CFC1	Orphanet:216718	Isolated congenitally uncorrected transposition of the great arteries
CFC1	Orphanet:216729	Congenitally uncorrected transposition of the great arteries with cardiac malformation
CFC1	Orphanet:244283	Biliary atresia with splenic malformation syndrome
CFC1	Orphanet:99042	Congenitally uncorrected transposition of the great arteries with coarctation

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
CFC1	HGNC:18292	ENSG00000136698	P0CG37	Cryptic protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFC1	Cryptic protein	NODAL coreceptor involved in the correct establishment of the left-right axis.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFC1	Other/Unknown	no		EGF, Cryptic/Cripto_CFC-dom

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
adenohypophysis	1
islet of Langerhans	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFC1	76		marker	islet of Langerhans, pituitary gland, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFC1	922

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFC1	P0CG37	64.18

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
Regulation of signaling by NODAL	1	951.7×	0.002	CFC1
Signaling by NODAL	1	496.5×	0.002	CFC1

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
nodal signaling pathway	1	1123.5×	0.004	CFC1
gastrulation	1	702.2×	0.004	CFC1
blood vessel development	1	374.5×	0.005	CFC1
determination of left/right symmetry	1	255.3×	0.006	CFC1
anterior/posterior pattern specification	1	181.2×	0.007	CFC1
heart development	1	78.8×	0.013	CFC1

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
CFC1	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	CFC1

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)
CFC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.