Dextrocardia

Summary

Dextrocardia (MONDO:0015661) is a disease with 6 cohort genes.

At a glance

• Cohort genes: 6
• ClinVar variants: 8
• Phenotypes (HPO): 26

Clinical features

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0001651	Dextrocardia	Obligate (100%)
HP:0001627	Abnormal heart morphology	Very frequent (80-99%)
HP:0003115	Abnormal EKG	Very frequent (80-99%)
HP:0010872	T-wave inversion	Very frequent (80-99%)
HP:0001696	Situs inversus totalis	Frequent (30-79%)
HP:0011603	Congenital malformation of the great arteries	Frequent (30-79%)
HP:0000069	Abnormality of the ureter	Occasional (5-29%)
HP:0001743	Abnormality of the spleen	Occasional (5-29%)
HP:0002101	Abnormal lung lobation	Occasional (5-29%)
HP:0002566	Intestinal malrotation	Occasional (5-29%)
HP:0004414	Abnormality of the pulmonary artery	Occasional (5-29%)
HP:0011615	Abnormality of pulmonary situs	Occasional (5-29%)
HP:0011620	Abnormality of abdominal situs	Occasional (5-29%)
HP:0012210	Abnormal renal morphology	Occasional (5-29%)
HP:0012243	Abnormal reproductive system morphology	Occasional (5-29%)
HP:0000238	Hydrocephalus	Very rare (<1-4%)
HP:0000384	Preauricular skin tag	Very rare (<1-4%)
HP:0000465	Webbed neck	Very rare (<1-4%)
HP:0000772	Abnormal rib morphology	Very rare (<1-4%)
HP:0001263	Global developmental delay	Very rare (<1-4%)
HP:0001374	Congenital hip dislocation	Very rare (<1-4%)
HP:0001760	Abnormal foot morphology	Very rare (<1-4%)
HP:0002245	Meckel diverticulum	Very rare (<1-4%)
HP:0002594	Pancreatic hypoplasia	Very rare (<1-4%)
HP:0003006	Neuroblastoma	Very rare (<1-4%)
HP:0008771	Aplasia/Hypoplasia of the ear	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	dextrocardia
Mondo ID	MONDO:0015661
MeSH	D003914
Orphanet	1666
DOID	DOID:9565
ICD-10-CM	Q24.0
ICD-11	1472687600
NCIT	C84669
SNOMED CT	27637000
UMLS	C0011813
MedGen	4255
GARD	0001827
MedDRA	10012592
Is cancer (heuristic)	no

Also known as: dextrocardia · dextrocardia (disease)

Data availability: 8 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › visceral heterotaxy › dextrocardia

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, 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, 12, 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

8 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
488411	NM_145020.5(CFAP53):c.301_473+1del	CFAP53	Likely pathogenic	no assertion criteria provided
977137	NM_001127392.3(MYRF):c.1786C>T (p.Gln596Ter)	MYRF	Likely pathogenic	criteria provided, single submitter
217132	NM_145020.5(CFAP53):c.472A>G (p.Arg158Gly)	CFAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
545561	NM_021785.6(RAI2):c.712G>A (p.Val238Ile)	RAI2	Uncertain significance	no assertion criteria provided
545556	NM_004850.5(ROCK2):c.3724C>T (p.Gln1242Ter)	ROCK2	Uncertain significance	no assertion criteria provided
545562	NM_007192.4(SUPT16H):c.956-1G>A	SUPT16H	Uncertain significance	no assertion criteria provided
545559	NM_001284236.3(ZFYVE16):c.1798G>A (p.Asp600Asn)	ZFYVE16	Uncertain significance	no assertion criteria provided
545560	NM_001284236.3(ZFYVE16):c.3755G>C (p.Gly1252Ala)	ZFYVE16	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUPT16H	Orphanet:261229	14q11.2 microduplication syndrome
MYRF	Orphanet:647811	Cardiac-urogenital syndrome
CFAP53	Orphanet:101063	Situs inversus totalis
CFAP53	Orphanet:157769	Situs ambiguus

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROCK2	HGNC:10252	ENSG00000134318	O75116	Rho-associated protein kinase 2	clinvar
SUPT16H	HGNC:11465	ENSG00000092201	Q9Y5B9	FACT complex subunit SPT16	clinvar
MYRF	HGNC:1181	ENSG00000124920	Q9Y2G1	Myelin regulatory factor	clinvar
ZFYVE16	HGNC:20756	ENSG00000039319	Q7Z3T8	Zinc finger FYVE domain-containing protein 16	clinvar
CFAP53	HGNC:26530	ENSG00000172361	Q96M91	Cilia- and flagella-associated protein 53	clinvar
RAI2	HGNC:9835	ENSG00000131831	Q9Y5P3	Retinoic acid-induced protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROCK2	Rho-associated protein kinase 2	Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.
SUPT16H	FACT complex subunit SPT16	Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes.
MYRF	Myelin regulatory factor	Constitutes a precursor of the transcription factor.
ZFYVE16	Zinc finger FYVE domain-containing protein 16	May be involved in regulating membrane trafficking in the endosomal pathway.
CFAP53	Cilia- and flagella-associated protein 53	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Protein-family classification

Druggable: 2 · Difficult: 3 · Unknown: 1 · Druggable fraction: 0.33

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	3	4.1×	0.107
Protease	1	6.1×	0.264
Kinase	1	4.6×	0.264
Other/Unknown	1	0.3×	0.993

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROCK2	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, PH_domain
SUPT16H	Protease	yes		Pept_M24, PH-like_dom_sf, RTT106/SPT16-like_middle_dom
MYRF	Transcription factor	no		p53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2
ZFYVE16	Transcription factor	no		Znf_FYVE, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
CFAP53	Transcription factor	no		CFAP53/TCHP, TPH_dom
RAI2	Other/Unknown	no		RAI2/SOBP

Expression context

Cohort genes with no expression data: 0.

6 cohort genes 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
inferior vagus X ganglion	2
calcaneal tendon	1
colonic epithelium	1
middle temporal gyrus	1
embryo	1
ganglionic eminence	1
ventricular zone	1
C1 segment of cervical spinal cord	1
middle frontal gyrus	1
corpus callosum	1
endothelial cell	1
bronchial epithelial cell	1
bronchus	1
left testis	1
left uterine tube	1
right lung	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROCK2	290	ubiquitous	marker	calcaneal tendon, colonic epithelium, middle temporal gyrus
SUPT16H	204	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
MYRF	223	ubiquitous	marker	middle frontal gyrus, C1 segment of cervical spinal cord, inferior vagus X ganglion
ZFYVE16	293	ubiquitous	marker	corpus callosum, endothelial cell, inferior vagus X ganglion
CFAP53	194	broad	marker	bronchial epithelial cell, bronchus, left testis
RAI2	260	broad	marker	left uterine tube, urethra, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SUPT16H	4,416
ROCK2	4,121
CFAP53	1,448
ZFYVE16	1,029
RAI2	998
MYRF	979

Structural data

PDB: 6 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ROCK2	O75116	21
SUPT16H	Q9Y5B9	17
MYRF	Q9Y2G1	2
ZFYVE16	Q7Z3T8	2
CFAP53	Q96M91	2
RAI2	Q9Y5P3	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 6 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHOBTB GTPase Cycle	1	271.9×	0.033	ROCK2
Sema4D in semaphorin signaling	1	223.9×	0.033	ROCK2
RHO GTPases Activate ROCKs	1	200.3×	0.033	ROCK2
Sema4D induced cell migration and growth-cone collapse	1	190.3×	0.033	ROCK2
RHOBTB1 GTPase cycle	1	158.6×	0.033	ROCK2
Semaphorin interactions	1	131.3×	0.033	ROCK2
EPHA-mediated growth cone collapse	1	126.9×	0.033	ROCK2
Pausing and recovery of Tat-mediated HIV elongation	1	122.8×	0.033	SUPT16H
Tat-mediated HIV elongation arrest and recovery	1	122.8×	0.033	SUPT16H
Signaling by BMP	1	119.0×	0.033	ZFYVE16
HIV elongation arrest and recovery	1	115.3×	0.033	SUPT16H
Pausing and recovery of HIV elongation	1	115.3×	0.033	SUPT16H
HIV Transcription Elongation	1	112.0×	0.033	SUPT16H
Viral Infection Pathways	2	20.5×	0.033	ROCK2, SUPT16H
Infectious disease	2	16.6×	0.033	ROCK2, SUPT16H
RHOH GTPase cycle	1	102.9×	0.034	ROCK2
EPHB-mediated forward signaling	1	88.5×	0.034	ROCK2
Formation of HIV-1 elongation complex containing HIV-1 Tat	1	86.5×	0.034	SUPT16H
Tat-mediated elongation of the HIV-1 transcript	1	86.5×	0.034	SUPT16H
Formation of HIV elongation complex in the absence of HIV Tat	1	82.8×	0.034	SUPT16H
Signaling by VEGF	1	73.2×	0.036	ROCK2
Formation of RNA Pol II elongation complex	1	64.5×	0.036	SUPT16H
RNA Polymerase II Transcription Elongation	1	64.5×	0.036	SUPT16H
TP53 Regulates Transcription of DNA Repair Genes	1	60.4×	0.036	SUPT16H
Transcription of the HIV genome	1	57.7×	0.036	SUPT16H
Late Phase of HIV Life Cycle	1	56.0×	0.036	SUPT16H
EPH-Ephrin signaling	1	55.2×	0.036	ROCK2
HIV Life Cycle	1	53.6×	0.036	SUPT16H
RHOB GTPase cycle	1	51.4×	0.036	ROCK2
RHOC GTPase cycle	1	48.8×	0.036	ROCK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 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 connective tissue growth factor production	1	2808.7×	0.015	ROCK2
regulation of angiotensin-activated signaling pathway	1	1404.3×	0.015	ROCK2
negative regulation of protein localization to lysosome	1	1404.3×	0.015	ROCK2
regulation of nervous system process	1	936.2×	0.015	ROCK2
cellular response to acetylcholine	1	936.2×	0.015	ROCK2
positive regulation of connective tissue replacement	1	936.2×	0.015	ROCK2
positive regulation of fibroblast growth factor production	1	702.2×	0.016	ROCK2
positive regulation of centrosome duplication	1	561.7×	0.016	ROCK2
negative regulation of bicellular tight junction assembly	1	561.7×	0.016	ROCK2
central nervous system myelin maintenance	1	468.1×	0.016	MYRF
regulation of cellular response to hypoxia	1	468.1×	0.016	ROCK2
regulation of cell junction assembly	1	401.2×	0.016	ROCK2
host-mediated perturbation of viral process	1	312.1×	0.016	ROCK2
response to transforming growth factor beta	1	312.1×	0.016	ROCK2
regulation of establishment of endothelial barrier	1	312.1×	0.016	ROCK2
response to angiotensin	1	312.1×	0.016	ROCK2
positive regulation of protein localization to early endosome	1	280.9×	0.016	ROCK2
positive regulation of amyloid precursor protein catabolic process	1	280.9×	0.016	ROCK2
embryonic morphogenesis	1	255.3×	0.016	ROCK2
negative regulation of biomineral tissue development	1	255.3×	0.016	ROCK2
positive regulation of DNA-templated transcription, elongation	1	216.1×	0.016	SUPT16H
epithelial cilium movement involved in determination of left/right asymmetry	1	216.1×	0.016	CFAP53
manchette assembly	1	216.1×	0.016	CFAP53
regulation of keratinocyte differentiation	1	200.6×	0.017	ROCK2
vesicle organization	1	187.2×	0.017	ZFYVE16
central nervous system myelination	1	165.2×	0.017	MYRF
negative regulation of nitric oxide biosynthetic process	1	165.2×	0.017	ROCK2
regulation of stress fiber assembly	1	165.2×	0.017	ROCK2
regulation of cell motility	1	165.2×	0.017	ROCK2
centrosome duplication	1	156.0×	0.017	ROCK2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 4

Druggability breadth: 2 of 6 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ROCK2	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ROCK2	52	4
SUPT16H	1	2
MYRF	0	0
ZFYVE16	0	0
CFAP53	0	0
RAI2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	ROCK2
FEDRATINIB	4	ROCK2
RUXOLITINIB	4	ROCK2
PALBOCICLIB	4	ROCK2
BELUMOSUDIL	4	ROCK2
TOFACITINIB CITRATE	4	ROCK2
BARICITINIB	4	ROCK2
TOFACITINIB	4	ROCK2
CAPIVASERTIB	4	ROCK2
CERITINIB	4	ROCK2
VANDETANIB	4	ROCK2
BOSUTINIB	4	ROCK2
UPADACITINIB	4	ROCK2
NETARSUDIL	4	ROCK2
SUNITINIB	4	ROCK2
CRIZOTINIB	4	ROCK2
MIDOSTAURIN	4	ROCK2
FASUDIL	3	ROCK2
AFURESERTIB	3	ROCK2
LINIFANIB	3	ROCK2
RIPASUDIL	3	ROCK2
ALVOCIDIB	3	ROCK2
DOVITINIB	3	ROCK2
LESTAURTINIB	3	ROCK2
FASUDIL HYDROCHLORIDE	2	ROCK2
PH-797804	2	ROCK2
FORETINIB	2	ROCK2
SAR-407899 FREE BASE	2	ROCK2
SU-014813	2	ROCK2
ZOTIRACICLIB	2	ROCK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ROCK2	788	Binding:783, Functional:3, ADMET:1, Toxicity:1
SUPT16H	8	Binding:8

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ROCK2	788

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
MOMELOTINIB	4	ROCK2
FEDRATINIB	4	ROCK2
RUXOLITINIB	4	ROCK2
PALBOCICLIB	4	ROCK2
BELUMOSUDIL	4	ROCK2
TOFACITINIB CITRATE	4	ROCK2
BARICITINIB	4	ROCK2
TOFACITINIB	4	ROCK2
CAPIVASERTIB	4	ROCK2
CERITINIB	4	ROCK2
VANDETANIB	4	ROCK2
BOSUTINIB	4	ROCK2
UPADACITINIB	4	ROCK2
NETARSUDIL	4	ROCK2
SUNITINIB	4	ROCK2
CRIZOTINIB	4	ROCK2
MIDOSTAURIN	4	ROCK2
FASUDIL	3	ROCK2
AFURESERTIB	3	ROCK2
LINIFANIB	3	ROCK2
RIPASUDIL	3	ROCK2
ALVOCIDIB	3	ROCK2
DOVITINIB	3	ROCK2
LESTAURTINIB	3	ROCK2
FASUDIL HYDROCHLORIDE	2	ROCK2
PH-797804	2	ROCK2
FORETINIB	2	ROCK2
SAR-407899 FREE BASE	2	ROCK2
SU-014813	2	ROCK2
ZOTIRACICLIB	2	ROCK2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ROCK2
B	Phased (≥1) drug, not yet approved	1	SUPT16H
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	MYRF, ZFYVE16, CFAP53, RAI2

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MYRF	0	—
ZFYVE16	0	—
CFAP53	0	—
RAI2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.