Disorder of development or morphogenesis

Summary

Disorder of development or morphogenesis (MONDO:0021147) is a disease (an umbrella term covering 190 Mondo subtypes) with 4 cohort genes (2 GWAS associations across 16 studies).

At a glance

• Umbrella term: 190 Mondo subtypes
• Cohort genes: 4
• GWAS associations: 2
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	disorder of development or morphogenesis
Mondo ID	MONDO:0021147
ICD-10-CM	Q00-Q99
UMLS	C0694457
MedGen	1843482
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 2 GWAS associations (16 studies).

Disease family

An umbrella term covering 190 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis

Related subtypes (11): psychiatric disorder, metabolic disease, premature aging syndrome, inflammatory disease, disorder of glycosylation, ulcer disease, mitochondrial disease, sleep disorder, perinatal disease, obstetric disorder, disease by molecular mechanism

Subtypes (190): precocious puberty, complex cortical dysplasia with other brain malformations, imperforate anus, microcephaly, demyelinating disease, hypospadias, bone development disease, primary basilar invagination, familial bicuspid aortic valve, camptodactyly of fingers, isolated congenital digital clubbing, aorta coarctation, gingival fibromatosis-progressive deafness syndrome, Eng-Strom syndrome, Morgagni-Stewart-Morel syndrome, familial partial lipodystrophy, Dunnigan type, megalodactyly, odontomatosis-aortae esophagus stenosis syndrome, otodental syndrome, oculodental syndrome, Rutherfurd type, spina bifida, steatocystoma multiplex-natal teeth syndrome, distal symphalangism, thumb deformity-alopecia-pigmentation anomaly syndrome, double uterus-hemivagina-renal agenesis syndrome, amelogenesis imperfecta type 1G, Bloom syndrome, cardiac valvular defect, developmental, isolated cerebellar hypoplasia/agenesis, cleft palate-stapes fixation-oligodontia syndrome, Jalili syndrome, craniodiaphyseal dysplasia, craniofacial dyssynostosis, deafness-oligodontia syndrome, duodenal atresia, Fowler syndrome, multiple intestinal atresia, natal teeth-intestinal pseudoobstruction-patent ductus syndrome, atresia of small intestine, mulibrey nanism, oculocerebral hypopigmentation syndrome, Cross type, familial osteodysplasia, Anderson type, pancreatic agenesis, postaxial polydactyly-dental and vertebral anomalies syndrome, familial primary pulmonary hypoplasia, renal tubular dysgenesis of genetic origin, Rothmund-Thomson syndrome, familial isolated congenital asplenia, subaortic stenosis, membranous, non-eruption of teeth-maxillary hypoplasia-genu valgum syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, CK syndrome, Ogden syndrome, Nance-Horan syndrome, colonic atresia, Aicardi syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, 46,XY complete gonadal dysgenesis, loose anagen syndrome, lung agenesis-heart defect-thumb anomalies syndrome, Chudley-McCullough syndrome, macrocephaly-autism syndrome, DNA ligase IV deficiency, horizontal gaze palsy with progressive scoliosis, cataract - congenital heart disease - neural tube defect syndrome, autosomal recessive frontotemporal pachygyria, craniofacial dysplasia - osteopenia syndrome, porencephaly-microcephaly-bilateral congenital cataract syndrome, congenital short bowel syndrome, familial median cleft of the upper and lower lips, progeroid features-hepatocellular carcinoma predisposition syndrome, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, aneurysm of sinus of Valsalva, blepharoptosis-cleft palate-ectrodactyly-dental anomalies syndrome, medullary sponge kidney, isolated congenital syngnathia, cleft lip and alveolus, diprosopus, T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency, high anorectal malformation, intermediate anorectal malformation, low anorectal malformation, microcephaly-polymicrogyria-corpus callosum agenesis syndrome, cordiform uterus, septate uterus, bicornuate uterus, uterine hypoplasia, agenesis and aplasia of uterine body, uterine cervical aplasia and agenesis, longitudinal vaginal septum, transverse vaginal septum, axial mesodermal dysplasia spectrum, multicystic dysplastic kidney, diabetic embryopathy, congenital microgastria, isolated cleft lip, cleft lip/palate, hereditary gingival fibromatosis, congenital bronchobiliary fistula, congenital hydrocephalus, maternal hyperthermia induced birth defects, diphallia, epibulbar lipodermoid-preauricular appendage-polythelia syndrome, bronchogenic cyst, duplication of urethra, hypohidrotic ectodermal dysplasia, Lowe-Kohn-Cohen syndrome, biliary atresia with splenic malformation syndrome, congenital pulmonary airway malformation, familial intestinal malrotation-facial anomalies syndrome, megalencephaly, cephalocele, cerebral cortical dysplasia, L1 syndrome, familial omphalocele syndrome with facial dysmorphism, penoscrotal transposition, pericardial and diaphragmatic defect, hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome, congenital deformities of limbs, familial isolated clinodactyly of fingers, congenital shoulder dislocation, congenital elbow dislocation, congenital knee dislocation, congenital patella dislocation, macrodactyly of fingers, macrodactyly of toes, upper limb hypertrophy, lower limb hypertrophy, duplication of the pituitary gland, diencephalic-mesencephalic junction dysplasia, steroid dehydrogenase deficiency-dental anomalies syndrome, congenital achiasma, tracheal agenesis, renal agenesis, hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome, isolated splenogonadal fusion, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, congenital bilateral absence of vas deferens, congenital portosystemic shunt, lissencephaly spectrum disorders, Berardinelli-Seip congenital lipodystrophy, congenital primary megaureter, craniorachischisis, vaginal atresia, bronchopulmonary dysplasia, dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome, aniridia, atypical Werner syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, anterior segment dysgenesis, congenital esophageal diverticulum, renal hypoplasia, renal dysplasia, overgrowth syndrome, developmental defect during embryogenesis, acalvaria, congenital aortic valve insufficiency, congenital anomaly of superior vena cava, congenital anomaly of hepatic vein, posterior hypospadias, isolated micropenis, isolated partial vaginal agenesis, anorectal malformation, pulmonary agenesis, congenital tricuspid malformation, Noonan syndrome and Noonan-related syndrome, coronary sinus stenosis, coronary sinus atresia, cartilage development disorder, syndactyly, polydactyly, brachydactyly, neurocristopathy, congenital absence of septum pellucidum, branchial arch disease, congenital anomaly of cardiovascular system, atelencephaly, aprosencephaly, aortic valve stenosis, hereditary lethal multiple congenital anomalies/dysmorphic syndrome, congenital agenesis of the scrotum, keratinization disease, lactation disease, COACH syndrome, constitutional delay of growth and puberty, isolated congenital femoral bifurcation, congenital peritoneal encapsulation, isolated short stature, congenital high airway obstruction syndrome

Genetics & variants

GWAS landscape

2 GWAS associations across 16 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs143602826	4e-08	LINC01899 - CBLN2	?
rs531422787	5e-08	LINC01904 - SLC25A3P3	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90474286	UK Biobank Whole-Genome Sequencing Consortium	2025	2,959	455,481	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90474273	UK Biobank Whole-Genome Sequencing Consortium	2025	1,798	456,642	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90474284	UK Biobank Whole-Genome Sequencing Consortium	2025	780	457,660	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90474267	UK Biobank Whole-Genome Sequencing Consortium	2025	624	457,816	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90651676	Liu TY	2025	490	236,370	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90482478	Verma A	2024	461	449,844	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90474290	UK Biobank Whole-Genome Sequencing Consortium	2025	379	458,061	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90482471	Verma A	2024	362	450,195	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90474270	UK Biobank Whole-Genome Sequencing Consortium	2025	337	458,103	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90474282	UK Biobank Whole-Genome Sequencing Consortium	2025	319	458,121	Whole-genome sequencing of 490,640 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intergenic_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs143602826	18	72010248	A>C,G	0.05	intergenic_variant	LINC01899 - CBLN2	4e-08	Tier 4: intronic/intergenic
rs531422787	18	1072929	A>C		intron_variant	LINC01904 - SLC25A3P3	5e-08	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
3075985	NM_016580.4(PCDH12):c.954C>A (p.Tyr318Ter)	RNF14	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4075118	NM_016580.4(PCDH12):c.2169_2181del (p.Val724fs)	PCDH12	Likely pathogenic	criteria provided, single submitter
1334941	NM_001170535.3(ATAD3A):c.1703A>T (p.Lys568Met)	ATAD3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4072103	NM_020297.4(ABCC9):c.573+2T>C	ABCC9	Uncertain significance	criteria provided, single submitter
4075152	NM_001170535.3(ATAD3A):c.1089+1G>C	ATAD3A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATAD3A	Orphanet:496790	Ocular anomalies-axonal neuropathy-developmental delay syndrome
ATAD3A	Orphanet:615983	Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome due to a point mutation
ATAD3A	Orphanet:615986	Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome due to biallelic deletions in the ATAD3 gene cluster
ATAD3A	Orphanet:656279	1p36.33 duplication syndrome
ABCC9	Orphanet:130	Brugada syndrome
ABCC9	Orphanet:1517	Cantú syndrome
ABCC9	Orphanet:154	Familial isolated dilated cardiomyopathy
ABCC9	Orphanet:334	Hereditary atrial fibrillation
PCDH12	Orphanet:319192	Diencephalic-mesencephalic junction dysplasia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF14	HGNC:10058	ENSG00000013561	Q9UBS8	E3 ubiquitin-protein ligase RNF14	clinvar
ATAD3A	HGNC:25567	ENSG00000197785	Q9NVI7	ATPase family AAA domain-containing protein 3A	clinvar
ABCC9	HGNC:60	ENSG00000069431	O60706	ATP-binding cassette sub-family C member 9	clinvar
PCDH12	HGNC:8657	ENSG00000113555	Q9NPG4	Protocadherin-12	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF14	E3 ubiquitin-protein ligase RNF14	E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of trans…
ATAD3A	ATPase family AAA domain-containing protein 3A	Essential for mitochondrial network organization, mitochondrial metabolism and cell growth at organism and cellular level.
ABCC9	ATP-binding cassette sub-family C member 9	Subunit of ATP-sensitive potassium channels (KATP).
PCDH12	Protocadherin-12	Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Transporter	1	19.4×	0.151
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF14	Transcription factor	no		Znf_RING, IBR_dom, RWD_dom
ATAD3A	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATAD3_N
ABCC9	Transporter	yes		ABCC8/9, ABCC9, ABC_transporter-like_ATP-bd
PCDH12	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Cadherin-like_sf

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	2
adrenal tissue	1
endothelial cell	1
oocyte	1
mucosa of transverse colon	1
sural nerve	1
hindlimb stylopod muscle	1
muscle of leg	1
olfactory bulb	1
tendon of biceps brachii	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF14	289	ubiquitous	marker	adrenal tissue, endothelial cell, oocyte
ATAD3A	247	ubiquitous	marker	sural nerve, gastrocnemius, mucosa of transverse colon
ABCC9	195	broad	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
PCDH12	217	broad	marker	tendon of biceps brachii, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATAD3A	2,519
ABCC9	1,728
RNF14	1,270
PCDH12	657

Structural data

PDB: 0 · AlphaFold-only: 4 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RNF14	Q9UBS8	83.00
ATAD3A	Q9NVI7	82.35
ABCC9	O60706	81.72
PCDH12	Q9NPG4	66.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 4 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	2855.0×	0.006	ABCC9
ATP sensitive Potassium channels	1	1427.5×	0.006	ABCC9
Inwardly rectifying K+ channels	1	356.9×	0.016	ABCC9
ABC transporter disorders	1	219.6×	0.019	ABCC9
Ion homeostasis	1	102.0×	0.033	ABCC9
Disorders of transmembrane transporters	1	69.6×	0.035	ABCC9
Potassium Channels	1	67.2×	0.035	ABCC9
ABC-family protein mediated transport	1	60.7×	0.035	ABCC9
Cardiac conduction	1	54.4×	0.035	ABCC9
Muscle contraction	1	38.6×	0.044	ABCC9
Class I MHC mediated antigen processing & presentation	1	35.0×	0.044	RNF14
Neuronal System	1	22.1×	0.063	ABCC9
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.069	RNF14
Adaptive Immune System	1	14.9×	0.080	RNF14
Transport of small molecules	1	12.6×	0.088	ABCC9
Disease	1	6.5×	0.148	ABCC9
Immune System	1	6.5×	0.148	RNF14

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to hydrogen sulfide	1	2106.5×	0.013	ABCC9
protein-RNA covalent cross-linking repair	1	1404.3×	0.013	RNF14
oxygen metabolic process	1	1053.2×	0.013	ABCC9
neuron recognition	1	842.6×	0.013	PCDH12
cellular response to chemical stress	1	702.2×	0.013	ABCC9
labyrinthine layer development	1	526.6×	0.013	PCDH12
HRI-mediated signaling	1	526.6×	0.013	ATAD3A
reactive oxygen species biosynthetic process	1	468.1×	0.013	ABCC9
cardiac conduction	1	421.3×	0.013	ABCC9
cardiac muscle cell contraction	1	421.3×	0.013	ABCC9
mitochondrion organization	2	75.9×	0.013	ATAD3A, ABCC9
negative regulation of PERK-mediated unfolded protein response	1	351.1×	0.013	ATAD3A
response to peptide	1	280.9×	0.013	ABCC9
fatty acid oxidation	1	263.3×	0.013	ABCC9
cellular response to potassium ion	1	263.3×	0.013	ABCC9
response to ATP	1	247.8×	0.013	ABCC9
regulation of androgen receptor signaling pathway	1	247.8×	0.013	RNF14
protein K6-linked ubiquitination	1	247.8×	0.013	RNF14
obsolete inorganic cation transmembrane transport	1	234.1×	0.013	ABCC9
cellular response to ATP	1	221.7×	0.014	ABCC9
negative regulation of apoptotic process	2	17.4×	0.014	ATAD3A, ABCC9
androgen receptor signaling pathway	1	175.5×	0.015	RNF14
negative regulation of blood pressure	1	162.0×	0.015	ABCC9
coronary vasculature development	1	156.0×	0.015	ABCC9
monoatomic cation transmembrane transport	1	156.0×	0.015	ABCC9
regulation of potassium ion transmembrane transport	1	156.0×	0.015	ABCC9
regulation of canonical Wnt signaling pathway	1	135.9×	0.016	RNF14
glycogen metabolic process	1	131.7×	0.016	PCDH12
calcium-dependent cell-cell adhesion	1	120.4×	0.016	PCDH12
rescue of stalled cytosolic ribosome	1	120.4×	0.016	RNF14

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
ABCC9	PINACIDIL ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC9	5	4
RNF14	0	0
ATAD3A	0	0
PCDH12	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PINACIDIL ANHYDROUS	4	ABCC9
GLYBURIDE	4	ABCC9
PROPAFENONE	4	ABCC9
CROMAKALIM	2	ABCC9
CLAMIKALANT	2	ABCC9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABCC9	61	Functional:46, Binding:15
ATAD3A	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

5 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)
PINACIDIL ANHYDROUS	4	ABCC9
GLYBURIDE	4	ABCC9
PROPAFENONE	4	ABCC9
CROMAKALIM	2	ABCC9
CLAMIKALANT	2	ABCC9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC9
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	3	RNF14, ATAD3A, PCDH12

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RNF14	0	—
ATAD3A	1	—
PCDH12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.