Acromegaloid facial appearance syndrome

Summary

Acromegaloid facial appearance syndrome (MONDO:0007051) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acromegaloid facial appearance syndrome
Mondo ID	MONDO:0007051
MeSH	C535655
OMIM	102150
Orphanet	965
SNOMED CT	720456009
UMLS	C0796280
MedGen	167116
GARD	0000501
Is cancer (heuristic)	no

Also known as: acromegaloid facial appearance syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome › acromegaloid facial appearance syndrome

Related subtypes (68): Hypoglossia-hypodactyly syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, campomelic dysplasia, cerebrocostomandibular syndrome, autosomal dominant popliteal pterygium syndrome, Pallister-Hall syndrome, autosomal dominant primary microcephaly, microgastria-limb reduction defect syndrome, Mobius syndrome, oculodentodigital dysplasia, Char syndrome, Prader-Willi syndrome, Silver-Russell syndrome, ulnar-mammary syndrome, short stature-wormian bones-dextrocardia syndrome, ablepharon macrostomia syndrome, Goodman syndrome, anophthalmia/microphthalmia-esophageal atresia syndrome, microphthalmia with limb anomalies, Antley-Bixler syndrome, campomelia, Cumming type, CHARGE syndrome, Toriello-Carey syndrome, Donnai-Barrow syndrome, lethal faciocardiomelic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, hypomandibular faciocranial dysostosis, isotretinoin-like syndrome, split hand-foot malformation 3, oculotrichoanal syndrome, Hennekam-Beemer syndrome, Mietens syndrome, Schinzel-Giedion syndrome, SHORT syndrome, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, occipital horn syndrome, hydrocephalus-costovertebral dysplasia-Sprengel anomaly syndrome, Potocki-Shaffer syndrome, Marshall-Smith syndrome, PHACE syndrome, Noonan syndrome-like disorder with loose anagen hair, branchiogenic deafness syndrome, combined immunodeficiency with faciooculoskeletal anomalies, chromosome 1p32-p31 deletion syndrome, Malan overgrowth syndrome, dysmorphism-conductive hearing loss-heart defect syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, short stature-heart defect-craniofacial anomalies syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, polyvalvular heart disease syndrome, Kallmann syndrome-heart disease syndrome, Meier-Gorlin syndrome, symptomatic form of Coffin-Lowry syndrome in female carriers, Prader-Willi-like syndrome, contractures-developmental delay-Pierre Robin syndrome, 22q11.2 deletion syndrome, Noonan syndrome, Carpenter syndrome, Bosley-Salih-Alorainy syndrome, Sotos syndrome, Robinow syndrome, King-Denborough syndrome, Weiss-Kruszka syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, 4q25 proximal deletion syndrome, restrictive dermopathy 1, mosaic SMO syndrome

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 4 · 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
ABCC9	Supportive	Autosomal dominant	acromegaloid facial appearance syndrome	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCC9	Orphanet:130	Brugada syndrome
ABCC9	Orphanet:1517	Cantú syndrome
ABCC9	Orphanet:154	Familial isolated dilated cardiomyopathy
ABCC9	Orphanet:334	Hereditary atrial fibrillation

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
ABCC9	HGNC:60	ENSG00000069431	O60706	ATP-binding cassette sub-family C member 9	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCC9	ATP-binding cassette sub-family C member 9	Subunit of ATP-sensitive potassium channels (KATP).

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCC9	Transporter	yes		ABCC8/9, ABCC9, ABC_transporter-like_ATP-bd

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
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCC9	195	broad	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC9	1,728

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABCC9	O60706	81.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	5710.0×	0.002	ABCC9
ATP sensitive Potassium channels	1	2855.0×	0.002	ABCC9
Inwardly rectifying K+ channels	1	713.8×	0.006	ABCC9
ABC transporter disorders	1	439.2×	0.007	ABCC9
Ion homeostasis	1	203.9×	0.013	ABCC9
Disorders of transmembrane transporters	1	139.3×	0.013	ABCC9
Potassium Channels	1	134.3×	0.013	ABCC9
ABC-family protein mediated transport	1	121.5×	0.013	ABCC9
Cardiac conduction	1	108.8×	0.013	ABCC9
Muscle contraction	1	77.2×	0.017	ABCC9
Neuronal System	1	44.3×	0.027	ABCC9
Transport of small molecules	1	25.1×	0.043	ABCC9
Disease	1	13.1×	0.076	ABCC9

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
response to hydrogen sulfide	1	8426.0×	0.004	ABCC9
oxygen metabolic process	1	4213.0×	0.004	ABCC9
cellular response to chemical stress	1	2808.7×	0.004	ABCC9
reactive oxygen species biosynthetic process	1	1872.4×	0.004	ABCC9
cardiac conduction	1	1685.2×	0.004	ABCC9
cardiac muscle cell contraction	1	1685.2×	0.004	ABCC9
response to peptide	1	1123.5×	0.004	ABCC9
fatty acid oxidation	1	1053.2×	0.004	ABCC9
cellular response to potassium ion	1	1053.2×	0.004	ABCC9
response to ATP	1	991.3×	0.004	ABCC9
obsolete inorganic cation transmembrane transport	1	936.2×	0.004	ABCC9
cellular response to ATP	1	887.0×	0.004	ABCC9
negative regulation of blood pressure	1	648.1×	0.004	ABCC9
coronary vasculature development	1	624.1×	0.004	ABCC9
monoatomic cation transmembrane transport	1	624.1×	0.004	ABCC9
regulation of potassium ion transmembrane transport	1	624.1×	0.004	ABCC9
response to hydrogen peroxide	1	468.1×	0.005	ABCC9
ATP metabolic process	1	468.1×	0.005	ABCC9
cellular respiration	1	432.1×	0.005	ABCC9
fibroblast proliferation	1	391.9×	0.005	ABCC9
heart morphogenesis	1	374.5×	0.005	ABCC9
vasodilation	1	366.4×	0.005	ABCC9
potassium ion import across plasma membrane	1	366.4×	0.005	ABCC9
action potential	1	358.6×	0.005	ABCC9
response to estrogen	1	343.9×	0.005	ABCC9
response to activity	1	324.1×	0.005	ABCC9
skeletal muscle tissue development	1	290.6×	0.005	ABCC9
cellular response to xenobiotic stimulus	1	240.7×	0.006	ABCC9
cellular response to calcium ion	1	200.6×	0.007	ABCC9
transport across blood-brain barrier	1	179.3×	0.007	ABCC9

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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

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

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

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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.