Heterotaxy, visceral, 12, autosomal

Summary

Heterotaxy, visceral, 12, autosomal (MONDO:0859222) is a disease with 1 cohort gene.

At a glance

• 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, 12, autosomal
Mondo ID	MONDO:0859222
OMIM	619702
DOID	DOID:0051026
UMLS	C5676898
MedGen	1803695
GARD	0026669
Is cancer (heuristic)	no

Data availability: 10 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › visceral heterotaxy › heterotaxy, visceral, 12, autosomal

Related subtypes (18): right atrial isomerism, situs inversus, heterotaxy, visceral, 1, X-linked, laterality defects, autosomal dominant, heterotaxy, visceral, 2, autosomal, heterotaxy, visceral, 3, autosomal, heterotaxy, visceral, 4, autosomal, heterotaxy, visceral, 6, autosomal, heterotaxy, visceral, 7, autosomal, heterotaxy, visceral, 8, autosomal, dextrocardia, levocardia, heterotaxy, visceral, 9, autosomal, with male infertility, heterotaxy, visceral, 10, autosomal, with male infertility, heterotaxy, visceral, 11, autosomal, with male infertility, heterotaxy, visceral, 5, autosomal, heterotaxy, visceral, 13, autosomal, heterotaxy, visceral, 14, autosomal

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:

5 pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1335922	NM_001354640.2(CIROP):c.1364TCT[1] (p.Phe456del)	CIROP	Pathogenic	no assertion criteria provided
1344488	NM_001354640.2(CIROP):c.1151C>T (p.Ser384Leu)	CIROP	Pathogenic	no assertion criteria provided
1344490	NM_001354640.2(CIROP):c.1037G>A (p.Trp346Ter)	CIROP	Pathogenic	no assertion criteria provided
1344493	NM_001354640.2(CIROP):c.1166G>T (p.Arg389Ile)	CIROP	Pathogenic	no assertion criteria provided
1344495	NM_001354640.2(CIROP):c.571C>T (p.Arg191Ter)	CIROP	Pathogenic	no assertion criteria provided
1804116	NM_001354640.2(CIROP):c.1331dup (p.Leu444fs)	CIROP	Likely pathogenic	criteria provided, single submitter
1335920	NM_001354640.2(CIROP):c.92C>T (p.Ser31Phe)	CIROP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2442172	NM_001354640.2(CIROP):c.64C>T (p.Arg22Ter)	CIROP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1804115	NM_001354640.2(CIROP):c.538G>C (p.Gly180Arg)	CIROP	Uncertain significance	criteria provided, single submitter
2582479	NM_001354640.2(CIROP):c.203A>G (p.Tyr68Cys)	CIROP	Uncertain significance	criteria provided, single submitter

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
CIROP	Orphanet:101063	Situs inversus totalis
CIROP	Orphanet:157769	Situs ambiguus

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
CIROP	HGNC:53647	ENSG00000283654	A0A1B0GTW7	Ciliated left-right organizer metallopeptidase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CIROP	Ciliated left-right organizer metallopeptidase	Putative metalloproteinase that plays a role in left-right patterning process.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CIROP	Protease	yes		Peptidase_M8

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
C1 segment of cervical spinal cord	1
mucosa of stomach	1
primary visual cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CIROP	49	tissue_specific	yes	mucosa of stomach, C1 segment of cervical spinal cord, primary visual cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CIROP	128

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CIROP	A0A1B0GTW7	73.73

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
establishment of left/right asymmetry	1	2106.5×	0.001	CIROP
cell adhesion	1	37.5×	0.029	CIROP
proteolysis	1	34.2×	0.029	CIROP

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
CIROP	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	1	CIROP
E	Difficult family or no structure, no drug	0

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)
CIROP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.