Antley-Bixler syndrome

Summary

Antley-Bixler syndrome (MONDO:0008803) is a disease with 3 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 3
• Phenotypes (HPO): 30

Clinical features

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0000358	Posteriorly rotated ears	Very frequent (80-99%)
HP:0000248	Brachycephaly	Very frequent (80-99%)
HP:0000270	Delayed cranial suture closure	Very frequent (80-99%)
HP:0000463	Anteverted nares	Very frequent (80-99%)
HP:0000772	Abnormal rib morphology	Very frequent (80-99%)
HP:0000774	Narrow chest	Very frequent (80-99%)
HP:0001166	Arachnodactyly	Very frequent (80-99%)
HP:0001387	Joint stiffness	Very frequent (80-99%)
HP:0002007	Frontal bossing	Very frequent (80-99%)
HP:0002980	Femoral bowing	Very frequent (80-99%)
HP:0003070	Elbow ankylosis	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0003275	Narrow pelvis bone	Very frequent (80-99%)
HP:0010669	Hypoplasia of the zygomatic bone	Very frequent (80-99%)
HP:0030680	Abnormal cardiovascular system morphology	Very frequent (80-99%)
HP:0100490	Camptodactyly of finger	Very frequent (80-99%)
HP:0000453	Choanal atresia	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0001363	Craniosynostosis	Frequent (30-79%)
HP:0012210	Abnormal renal morphology	Frequent (30-79%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000262	Turricephaly	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0001883	Talipes	Occasional (5-29%)
HP:0002757	Recurrent fractures	Occasional (5-29%)
HP:0009891	Underdeveloped supraorbital ridges	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Antley-Bixler syndrome
Mondo ID	MONDO:0008803
Orphanet	83
DOID	DOID:0050462, DOID:0081289
ICD-11	2027710139
SNOMED CT	62964007
UMLS	C5234850
MedGen	1714404
GARD	0005826
NORD	792
Is cancer (heuristic)	no

Also known as: Antley Bixler syndrome · osteodysgenesis, multisynostotic with fractures · trapezoidocephaly synostosis syndrome

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › craniosynostosis syndrome, autosomal recessive › Antley-Bixler syndrome

Related subtypes (1): cranioectodermal dysplasia

Subtypes (2): Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis

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: 58 · Orphanet: 16 · 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
POR	Definitive	Autosomal recessive	Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis	7
PORCN	Definitive	Autosomal recessive	Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis	13
FGFR2	Strong	Autosomal dominant	Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis	38

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PORCN	Orphanet:2092	Focal dermal hypoplasia
PORCN	Orphanet:98938	Colobomatous microphthalmia
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3
POR	Orphanet:63269	Antley-Bixler syndrome with genital anomaly and disorder of steroidogenesis
POR	Orphanet:95699	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PORCN	HGNC:17652	ENSG00000102312	Q9H237	Protein-serine O-palmitoleoyltransferase porcupine	gencc
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gencc
POR	HGNC:9208	ENSG00000127948	P16435	NADPH–cytochrome P450 reductase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PORCN	Protein-serine O-palmitoleoyltransferase porcupine	Protein-serine O-palmitoleoyltransferase that acts as a key regulator of the Wnt signaling pathway by mediating the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1(9Z)), to Wnt proteins.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
POR	NADPH–cytochrome P450 reductase	This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes.

Protein-family classification

Druggable: 3 · 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
Enzyme (other)	2	8.0×	0.039
Kinase	1	9.2×	0.104

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PORCN	Enzyme (other)	yes	2.3.1.250	MBOAT_fam, LPLAT_7/PORCN-like
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
POR	Enzyme (other)	yes	1.6.2.4	Flavdoxin-like, OxRdtase_FAD/NAD-bd, Flavoprot_Pyr_Nucl_cyt_Rdtase

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right adrenal gland	2
lower esophagus mucosa	1
right adrenal gland cortex	1
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1
adrenal tissue	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PORCN	184	ubiquitous	marker	lower esophagus mucosa, right adrenal gland cortex, right adrenal gland
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
POR	266	ubiquitous	marker	adrenal tissue, right lobe of liver, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POR	2,263
PORCN	802
FGFR2	449

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR2	P21802	63
POR	P16435	9
PORCN	Q9H237	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 3 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
Signaling by FGFR2 amplification mutants	1	3806.7×	0.003	FGFR2
Signaling by FGFR2 fusions	1	3806.7×	0.003	FGFR2
LGK974 inhibits PORCN	1	1903.3×	0.004	PORCN
FGFR2b ligand binding and activation	1	380.7×	0.012	FGFR2
FGFR2c ligand binding and activation	1	292.8×	0.012	FGFR2
Cytochrome P450 - arranged by substrate type	1	237.9×	0.012	POR
Activated point mutants of FGFR2	1	223.9×	0.012	FGFR2
Phospholipase C-mediated cascade; FGFR2	1	211.5×	0.012	FGFR2
Signaling by FGFR2 IIIa TM	1	200.3×	0.012	FGFR2
PI-3K cascade:FGFR2	1	165.5×	0.012	FGFR2
SHC-mediated cascade:FGFR2	1	158.6×	0.012	FGFR2
FRS-mediated FGFR2 signaling	1	146.4×	0.012	FGFR2
WNT ligand biogenesis and trafficking	1	141.0×	0.012	PORCN
FGFR2 alternative splicing	1	141.0×	0.012	FGFR2
Negative regulation of FGFR2 signaling	1	122.8×	0.013	FGFR2
PI3K Cascade	1	90.6×	0.016	FGFR2
Signaling by FGFR2 in disease	1	88.5×	0.016	FGFR2
Phase I - Functionalization of compounds	1	73.2×	0.018	POR
Biological oxidations	1	43.3×	0.028	POR
Constitutive Signaling by Aberrant PI3K in Cancer	1	42.3×	0.028	FGFR2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	32.3×	0.035	FGFR2
PIP3 activates AKT signaling	1	22.3×	0.048	FGFR2
RAF/MAP kinase cascade	1	20.4×	0.050	FGFR2
Metabolism	1	3.9×	0.237	POR

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	5617.3×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	5617.3×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	5617.3×	0.003	FGFR2
nitrate catabolic process	1	5617.3×	0.003	POR
lateral sprouting from an epithelium	1	5617.3×	0.003	FGFR2
positive regulation of growth plate cartilage chondrocyte proliferation	1	5617.3×	0.003	POR
positive regulation of steroid hormone biosynthetic process	1	5617.3×	0.003	POR
orbitofrontal cortex development	1	2808.7×	0.003	FGFR2
protein palmitoleylation	1	2808.7×	0.003	PORCN
nitric oxide catabolic process	1	2808.7×	0.003	POR
prostate gland morphogenesis	1	2808.7×	0.003	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	2808.7×	0.003	FGFR2
mammary gland bud formation	1	2808.7×	0.003	FGFR2
branch elongation involved in salivary gland morphogenesis	1	2808.7×	0.003	FGFR2
mesenchymal cell differentiation involved in lung development	1	2808.7×	0.003	FGFR2
organofluorine metabolic process	1	2808.7×	0.003	POR
regulation of osteoblast proliferation	1	1872.4×	0.003	FGFR2
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1872.4×	0.003	FGFR2
prostate epithelial cord elongation	1	1872.4×	0.003	FGFR2
Wnt protein secretion	1	1872.4×	0.003	PORCN
P450-containing electron transport chain	1	1872.4×	0.003	POR
ventricular zone neuroblast division	1	1404.3×	0.003	FGFR2
embryonic organ morphogenesis	1	1404.3×	0.003	FGFR2
reproductive structure development	1	1404.3×	0.003	FGFR2
regulation of morphogenesis of a branching structure	1	1404.3×	0.003	FGFR2
demethylation	1	1404.3×	0.003	POR
protein lipidation	1	1123.5×	0.003	PORCN
positive regulation of phospholipase activity	1	1123.5×	0.003	FGFR2
regulation of smooth muscle cell differentiation	1	1123.5×	0.003	FGFR2
branching involved in prostate gland morphogenesis	1	1123.5×	0.003	FGFR2

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 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
FGFR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR2	59	4
PORCN	2	2
POR	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR2
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
LESTAURTINIB	3	FGFR2
WNT-974	2	PORCN
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
FGFR2	966	Binding:940, Functional:22, ADMET:4
PORCN	31	Binding:31
POR	21	ADMET:14, Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PORCN	2.3.1.250	[Wnt protein] O-palmitoleoyl transferase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
POR	1.6.2.4	NADPH-hemoprotein reductase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FGFR2	966

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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)
PONATINIB	4	FGFR2
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
LESTAURTINIB	3	FGFR2
WNT-974	2	PORCN
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FGFR2
B	Phased (≥1) drug, not yet approved	2	PORCN, POR
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.