isolated Pierre-Robin syndrome

Summary

isolated Pierre-Robin syndrome (MONDO:0009869) is a disease caused by SOX9 (GenCC Definitive), with 8 cohort genes and 6 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: SOX9 (GenCC Definitive)
• Cohort genes: 8
• ClinVar variants: 13
• Phenotypes (HPO): 21
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

15 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Prevalence at birth	1-9 / 100 000	5	Europe	Validated
Point prevalence	1-9 / 100 000		France	Validated
Prevalence at birth	1-9 / 100 000	8	France	Validated
Prevalence at birth	1-5 / 10 000	12.4	Germany	Validated
Prevalence at birth	1-9 / 100 000	3.5	Denmark	Validated
Prevalence at birth	1-9 / 100 000	4.5	Sweden	Validated
Prevalence at birth	1-9 / 100 000	5.9	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	6.4	Netherlands	Validated
Prevalence at birth	1-5 / 10 000	18.8	Australia	Validated
Point prevalence	1-9 / 100 000		United Kingdom	Not yet validated
Point prevalence	1-9 / 100 000		Denmark	Not yet validated
Point prevalence	1-9 / 100 000		Sweden	Not yet validated
Point prevalence	1-9 / 100 000		United States	Not yet validated
Prevalence at birth	1-9 / 100 000	7.9	United States	Not yet validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000162	Glossoptosis	Very frequent (80-99%)
HP:0000175	Cleft palate	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001561	Polyhydramnios	Frequent (30-79%)
HP:0002643	Neonatal respiratory distress	Frequent (30-79%)
HP:0002781	Upper airway obstruction	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0012418	Hypoxemia	Frequent (30-79%)
HP:0000453	Choanal atresia	Occasional (5-29%)
HP:0000961	Cyanosis	Occasional (5-29%)
HP:0001601	Laryngomalacia	Occasional (5-29%)
HP:0001607	Subglottic stenosis	Occasional (5-29%)
HP:0001648	Cor pulmonale	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002777	Tracheal stenosis	Occasional (5-29%)
HP:0002779	Tracheomalacia	Occasional (5-29%)
HP:0002780	Bronchomalacia	Occasional (5-29%)
HP:0004890	Elevated pulmonary artery pressure	Occasional (5-29%)
HP:0010307	Stridor	Occasional (5-29%)
HP:0010535	Sleep apnea	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated Pierre-Robin syndrome
Mondo ID	MONDO:0009869
MeSH	D010855
OMIM	261800
Orphanet	718
ICD-11	136361299
NCIT	C85010
SNOMED CT	4602007
UMLS	C0031900
MedGen	19310
GARD	0004347
NORD	1579
Is cancer (heuristic)	no

Also known as: glossoptosis, micrognathia, and cleft palate · isolated Pierre Robin sequence · Pierre Robin Sequence · Pierre Robin syndrome skeletal dysplasia polydactyly

Data availability: 13 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › isolated Pierre-Robin syndrome

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Subtypes (1): radial defect robin sequence

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

13 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
267851	46;XX;ins(5;6)(p13;p24p25)dn		Pathogenic	criteria provided, single submitter
1047880	GRCh37/hg19 7q21.12-22.1(chr7:87477185-100333327)	ASB4	Pathogenic	criteria provided, single submitter
268156	NM_001375380.1(EBF3):c.488G>A (p.Arg163Gln)	EBF3	Pathogenic	criteria provided, multiple submitters, no conflicts
218934	t(12;19)(q24.21;q12)	MED13L	Pathogenic	criteria provided, single submitter
1334402	NM_001366521.1(ATP2B1):c.3060+2T>G	ATP2B1	Likely pathogenic	criteria provided, single submitter
1334403	NM_001366521.1(ATP2B1):c.2938G>T (p.Val980Leu)	ATP2B1	Likely pathogenic	criteria provided, single submitter
562231	Single allele	GPS2	Likely pathogenic	no assertion criteria provided
981739	NM_003091.4(SNRPB):c.560-1G>T	SNRPB	Likely pathogenic	no assertion criteria provided
267836	46;XY;t(1;6)(q23;q13)dn		Uncertain significance	criteria provided, single submitter
267878	46;XX;t(1;13)(p36.1;q12.1)dn		Uncertain significance	criteria provided, single submitter
267909	46;XX;t(6;7;17)(p23;p22;q25)pat		Uncertain significance	criteria provided, single submitter
268030	46;XY;t(10;17)(p13;q23)dn		Uncertain significance	criteria provided, single submitter
559503	GRCh37/hg19 2q31.1(chr2:172344870-173038935)x4	CYBRD1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 12 · 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
SOX9	Definitive	Autosomal dominant	isolated Pierre-Robin syndrome	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX9	Orphanet:140	Campomelic dysplasia
SOX9	Orphanet:2138	46,XX ovotesticular difference of sex development
SOX9	Orphanet:242	46,XY complete gonadal dysgenesis
SOX9	Orphanet:251510	46,XY partial gonadal dysgenesis
SOX9	Orphanet:393	46,XX testicular difference of sex development
SOX9	Orphanet:718	Isolated Pierre Robin sequence
SNRPB	Orphanet:1393	Cerebrocostomandibular syndrome
EBF3	Orphanet:658843	Developmental delay-ataxia-hypotonia-facial dysmorphism syndrome
EBF3	Orphanet:96148	Distal deletion 10q syndrome
MED13L	Orphanet:216718	Isolated congenitally uncorrected transposition of the great arteries
MED13L	Orphanet:369891	Developmental delay-facial dysmorphism syndrome due to MED13L deficiency
ATP2B1	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	gencc
SNRPB	HGNC:11153	ENSG00000125835	P14678	Small nuclear ribonucleoprotein-associated proteins B and B'	clinvar
ASB4	HGNC:16009	ENSG00000005981	Q9Y574	Ankyrin repeat and SOCS box protein 4	clinvar
EBF3	HGNC:19087	ENSG00000108001	Q9H4W6	Transcription factor COE3	clinvar
CYBRD1	HGNC:20797	ENSG00000071967	Q53TN4	Plasma membrane ascorbate-dependent reductase CYBRD1	clinvar
MED13L	HGNC:22962	ENSG00000123066	Q71F56	Mediator of RNA polymerase II transcription subunit 13-like	clinvar
GPS2	HGNC:4550	ENSG00000132522	Q13227	G protein pathway suppressor 2	clinvar
ATP2B1	HGNC:814	ENSG00000070961	P20020	Plasma membrane calcium-transporting ATPase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
SNRPB	Small nuclear ribonucleoprotein-associated proteins B and B'	Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
ASB4	Ankyrin repeat and SOCS box protein 4	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
EBF3	Transcription factor COE3	Transcriptional activator.
CYBRD1	Plasma membrane ascorbate-dependent reductase CYBRD1	Plasma membrane reductase that uses cytoplasmic ascorbate as an electron donor to reduce extracellular Fe(3+) into Fe(2+).
MED13L	Mediator of RNA polymerase II transcription subunit 13-like	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
GPS2	G protein pathway suppressor 2	Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting ‘Lys-63’-linked ubiquitination.
ATP2B1	Plasma membrane calcium-transporting ATPase 1	Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis.

Protein-family classification

Druggable: 1 · Difficult: 4 · Unknown: 3 · Druggable fraction: 0.12

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	3.1×	0.249
Scaffold/PPI	1	2.2×	0.669
Enzyme (other)	1	1.5×	0.669
Other/Unknown	3	0.7×	0.919

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf
SNRPB	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, snRNP-assoc_SmB/SmN
ASB4	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
EBF3	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold
CYBRD1	Enzyme (other)	yes	7.2.1.3	Cyt_b561/ferric_Rdtase_TM, CYB561/CYBRD1-like
MED13L	Other/Unknown	no		Med13_C, Mediator_Med13_N, MID_MedPIWI
GPS2	Other/Unknown	no		GPS2
ATP2B1	Transcription factor	no	7.2.2.10	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, ATPase_P-typ_cation-transptr_C

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
cranial nerve II	1
hair follicle	1
ventricular zone	1
endometrium epithelium	1
granulocyte	1
mucosa of transverse colon	1
adrenal tissue	1
right adrenal gland	1
right adrenal gland cortex	1
subcutaneous adipose tissue	1
tendon of biceps brachii	1
tibialis anterior	1
germinal epithelium of ovary	1
skin of hip	1
colonic epithelium	1
tendon	1
left testis	1
right testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOX9	274	ubiquitous	marker	ventricular zone, cranial nerve II, hair follicle
SNRPB	291	ubiquitous	marker	endometrium epithelium, granulocyte, mucosa of transverse colon
ASB4	168	tissue_specific	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland
EBF3	193	broad	marker	tibialis anterior, subcutaneous adipose tissue, tendon of biceps brachii
CYBRD1	262	ubiquitous	marker	calcaneal tendon, germinal epithelium of ovary, skin of hip
MED13L	297	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
GPS2	134	ubiquitous	marker	left testis, right testis, sural nerve
ATP2B1	296	ubiquitous	marker	frontal pole, Brodmann (1909) area 23, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOX9	4,935
SNRPB	3,769
ATP2B1	3,055
GPS2	1,837
ASB4	1,645
MED13L	1,606
CYBRD1	905
EBF3	655

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SNRPB	P14678	75
EBF3	Q9H4W6	2
CYBRD1	Q53TN4	2
SOX9	P48436	1
GPS2	Q13227	1
ATP2B1	P20020	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ASB4	Q9Y574	92.69
MED13L	Q71F56	56.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 72. Enrichment computed across 8 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of MECP2 binding ability to the NCoR/SMRT complex	1	233.1×	0.083	GPS2
SLBP independent Processing of Histone Pre-mRNAs	1	163.1×	0.083	SNRPB
Processing of Capped Intronless Pre-mRNA	1	148.3×	0.083	SNRPB
SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	1	148.3×	0.083	SNRPB
Reduction of cytosolic Ca++ levels	1	135.9×	0.083	ATP2B1
Platelet calcium homeostasis	1	102.0×	0.083	ATP2B1
Transcriptional regulation of testis differentiation	1	102.0×	0.083	SOX9
Metabolism of non-coding RNA	1	90.6×	0.083	SNRPB
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	85.9×	0.083	SOX9
PPARA activates gene expression	2	27.0×	0.083	MED13L, GPS2
Regulation of MECP2 expression and activity	1	52.6×	0.085	GPS2
Iron uptake and transport	1	49.4×	0.085	CYBRD1
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	44.1×	0.085	GPS2
Sensory processing of sound	1	44.1×	0.085	ATP2B1
Developmental Lineage of Pancreatic Acinar Cells	1	42.9×	0.085	SOX9
Platelet homeostasis	1	39.8×	0.085	ATP2B1
Transcriptional regulation by RUNX2	1	36.2×	0.085	SOX9
Deactivation of the beta-catenin transactivating complex	1	33.3×	0.085	SOX9
Developmental Lineage of Pancreatic Ductal Cells	1	32.6×	0.085	SOX9
mRNA Splicing - Minor Pathway	1	32.0×	0.085	SNRPB
Developmental Cell Lineages	1	32.0×	0.085	SOX9
SARS-CoV-2 modulates host translation machinery	1	32.0×	0.085	SNRPB
RNA Polymerase II Transcription Termination	1	31.4×	0.085	SNRPB
snRNP Assembly	1	30.2×	0.085	SNRPB
Ion transport by P-type ATPases	1	29.7×	0.085	ATP2B1
Ion homeostasis	1	29.1×	0.085	ATP2B1
Respiratory Syncytial Virus Infection Pathway	1	28.1×	0.085	MED13L
Viral Infection Pathways	2	8.8×	0.085	SNRPB, MED13L
Infectious disease	2	7.1×	0.085	SNRPB, MED13L
RNA Polymerase II Transcription	2	6.4×	0.085	SNRPB, SOX9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
reductive iron assimilation	1	2106.5×	0.013	CYBRD1
negative regulation of immune system process	1	1053.2×	0.013	SOX9
epithelial cell proliferation involved in prostatic bud elongation	1	1053.2×	0.013	SOX9
regulation of cell proliferation involved in tissue homeostasis	1	1053.2×	0.013	SOX9
regulation of branching involved in lung morphogenesis	1	1053.2×	0.013	SOX9
cell proliferation involved in heart morphogenesis	1	1053.2×	0.013	SOX9
regulation of epithelial cell proliferation involved in lung morphogenesis	1	1053.2×	0.013	SOX9
heart valve formation	1	702.2×	0.013	SOX9
neural crest cell fate specification	1	702.2×	0.013	SOX9
male germ-line sex determination	1	702.2×	0.013	SOX9
intrahepatic bile duct development	1	702.2×	0.013	SOX9
bronchus cartilage development	1	702.2×	0.013	SOX9
lung smooth muscle development	1	702.2×	0.013	SOX9
ureter urothelium development	1	702.2×	0.013	SOX9
ureter smooth muscle cell differentiation	1	702.2×	0.013	SOX9
ascorbate homeostasis	1	702.2×	0.013	CYBRD1
negative regulation of beta-catenin-TCF complex assembly	1	702.2×	0.013	SOX9
glial cell fate specification	1	526.6×	0.013	SOX9
cellular response to heparin	1	526.6×	0.013	SOX9
renal vesicle induction	1	526.6×	0.013	SOX9
positive regulation of kidney development	1	526.6×	0.013	SOX9
negative regulation of protein K63-linked ubiquitination	1	526.6×	0.013	GPS2
regulation of vascular associated smooth muscle contraction	1	421.3×	0.013	ATP2B1
chondrocyte hypertrophy	1	421.3×	0.013	SOX9
growth plate cartilage chondrocyte growth	1	421.3×	0.013	SOX9
astrocyte fate commitment	1	421.3×	0.013	SOX9
trachea cartilage development	1	421.3×	0.013	SOX9
morphogenesis of a branching epithelium	1	421.3×	0.013	SOX9
Harderian gland development	1	421.3×	0.013	SOX9
metanephric nephron tubule formation	1	421.3×	0.013	SOX9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8

Druggability breadth: 2 of 8 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SOX9	0	0
SNRPB	0	0
ASB4	0	0
EBF3	0	0
CYBRD1	0	0
MED13L	0	0
GPS2	0	0
ATP2B1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
SNRPB	6	Binding:6
SOX9	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYBRD1	7.2.1.3	ascorbate ferrireductase (transmembrane)
ATP2B1	7.2.2.10	P-type Ca2+ transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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	1	CYBRD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	7	SOX9, SNRPB, ASB4, EBF3, MED13L, GPS2, ATP2B1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SOX9	3	—
SNRPB	6	—
ASB4	0	—
EBF3	0	—
CYBRD1	0	—
MED13L	0	—
GPS2	0	—
ATP2B1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07257276	Not specified	ACTIVE_NOT_RECRUITING	3D-CT-Based Prediction of Difficult Laryngoscopy in Infants With Pierre Robin Sequence
NCT01690078	Not specified	COMPLETED	Functional Modeling of the Pediatric Airway
NCT02432638	Not specified	WITHDRAWN	Pierre Robin Sequence Outcome Assessment Multi Institutional Study
NCT03423017	Not specified	COMPLETED	Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence
NCT04422067	Not specified	COMPLETED	Usefulness of Cephalometry in the Second and Third Trimester of Pregnancy in the Diagnosis of Fetal Microretrognathia
NCT07604818	Not specified	COMPLETED	Comparison of Sucking in Premature Infants and Infants With Pierre Robin Sequence