Proximal 16p11.2 microdeletion syndrome

Summary

Proximal 16p11.2 microdeletion syndrome (MONDO:0012756) is a disease with 10 cohort genes and 2 clinical trials. The dominant Reactome pathway is Hemostasis (3 cohort genes). Top therapeutic interventions include arbaclofen.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 10
• ClinVar variants: 24
• Phenotypes (HPO): 52
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	20	Europe	Validated
Point prevalence	1-5 / 10 000	20	United States	Validated

Signs & symptoms

Clinical features (HPO)

52 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000708	Atypical behavior	Very frequent (80-99%)
HP:0000729	Autistic behavior	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001256	Intellectual disability, mild	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001328	Specific learning disability	Frequent (30-79%)
HP:0006863	Severe expressive language delay	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0009088	Speech articulation difficulties	Frequent (30-79%)
HP:0011351	Moderate receptive language delay	Frequent (30-79%)
HP:0410263	Brain imaging abnormality	Frequent (30-79%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000337	Broad forehead	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000733	Abnormal repetitive mannerisms	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001266	Choreoathetosis	Occasional (5-29%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001513	Obesity	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001646	Abnormal aortic valve morphology	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002280	Enlarged cisterna magna	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002691	Platybasia	Occasional (5-29%)
HP:0003468	Abnormal vertebral morphology	Occasional (5-29%)
HP:0007099	Chiari type I malformation	Occasional (5-29%)
HP:0007166	Paroxysmal dyskinesia	Occasional (5-29%)
HP:0011098	Speech apraxia	Occasional (5-29%)
HP:0011800	Midface retrusion	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0012760	Reduced social responsiveness	Occasional (5-29%)
HP:0100702	Arachnoid cyst	Occasional (5-29%)
HP:0000003	Multicystic kidney dysplasia	Very rare (<1-4%)
HP:0000175	Cleft palate	Very rare (<1-4%)
HP:0000776	Congenital diaphragmatic hernia	Very rare (<1-4%)
HP:0000902	Rib fusion	Very rare (<1-4%)
HP:0001161	Hand polydactyly	Very rare (<1-4%)
HP:0001363	Craniosynostosis	Very rare (<1-4%)
HP:0001651	Dextrocardia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	proximal 16p11.2 microdeletion syndrome
Mondo ID	MONDO:0012756
MeSH	C579850
OMIM	611913
Orphanet	261197
DOID	DOID:0070515
NCIT	C120408
SNOMED CT	699307007, 718227006
UMLS	C3150154
MedGen	461504
GARD	0010740
Is cancer (heuristic)	no

Also known as: 16p11.2 deletion syndrome · autism susceptibility 14A · chromosome 16p11.2 deletion syndrome · chromosome 16p11.2 deletion syndrome, 593kb · Del(16)(p11.2) · microdeletion 16p11.2 · monosomy 16p11.2 · proximal del(16)(p11.2) · proximal monosomy 16p11.2

Data availability: 24 ClinVar variants · 7 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal deletion › partial deletion of chromosome 16 › partial deletion of the short arm of chromosome 16 › proximal 16p11.2 microdeletion syndrome

Related subtypes (8): chromosome 16p12.1 deletion syndrome, 520kb, alpha thalassemia-intellectual disability syndrome type 1, autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis, distal 16p11.2 microdeletion syndrome, chromosome 16p12.2-p11.2 deletion syndrome, 16p13.11 microdeletion syndrome, chromosome 16p13.3 deletion syndrome, Hao-Fountain syndrome due to 16p13.2 microdeletion

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

24 retrieved; paginated sample, class counts are floors:

20 pathogenic, 1 likely pathogenic, 1 uncertain significance, 1 not provided, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1684661	NC_000016.10:g.29640592_30187862del	ALDOA	Pathogenic	criteria provided, single submitter
1703545	GRCh37/hg19 16p11.2(chr16:29580020-30177999)	ALDOA	Pathogenic	no assertion criteria provided
1703556	GRCh37/hg19 16p11.2(chr16:29580020-30177916)	ALDOA	Pathogenic	no assertion criteria provided
1703578	GRCh37/hg19 16p11.2(chr16:29567295-30178406)	ALDOA	Pathogenic	no assertion criteria provided
4056087	NC_000016.9:g.(?29477897)(30199899_?)del	ALDOA	Pathogenic	criteria provided, single submitter
625602	GRCh37/hg19 16p11.2(chr16:29042050-30199025)	ALDOA	Pathogenic	criteria provided, single submitter
625605	GRCh37/hg19 16p11.2(chr16:29673203-30133233)	ALDOA	Pathogenic	criteria provided, single submitter
625606	GRCh37/hg19 16p11.2(chr16:29678569-30199402)	ALDOA	Pathogenic	criteria provided, single submitter
625650	GRCh37/hg19 16p11.2(chr16:29595483-30199713)	ALDOA	Pathogenic	criteria provided, single submitter
625688	GRCh37/hg19 16p11.2(chr16:29673203-30199713)	ALDOA	Pathogenic	criteria provided, single submitter
666439	GRCh37/hg19 16p11.2(chr16:29674336-30199351)x1	ALDOA	Pathogenic	criteria provided, single submitter
666440	GRCh37/hg19 16p11.2(chr16:29674336-30198123)x1	ALDOA	Pathogenic	criteria provided, single submitter
2576522	GRCh37/hg19 16p11.2(chr16:29656684-30197341)x1	CDIPT	Pathogenic	no assertion criteria provided
1703589	GRCh37/hg19 16p12.2(chr16:21801889-22431357)	CDR2	Pathogenic	no assertion criteria provided
41405	16p11.2 recurrent region (BP4-BP5)	LOC116276452	Pathogenic	no assertion criteria provided
3024180	GRCh38/hg38 16p11.2(chr16:29329272-30178707)x1	LOC130058759	Pathogenic	criteria provided, single submitter
4820054	NC_000016.10:g.(29430690_29568654)_(30188576_30308346)del	LOC130058779	Pathogenic	criteria provided, single submitter
812191	Single allele	NFATC2IP	Pathogenic	criteria provided, single submitter
1703534	GRCh37/hg19 16p12.2(chr16:21801889-22710614)	NPIPB5	Pathogenic	no assertion criteria provided
1077186	Single allele	PAGR1	Pathogenic	criteria provided, single submitter
1077191	Single allele	ATP2A1	Likely pathogenic	criteria provided, single submitter
974579	Single allele	ALDOA	risk factor	criteria provided, single submitter
1691337	NM_005411.5(SFTPA1):c.292G>A (p.Gly98Arg)	SFTPA1	Uncertain significance	criteria provided, single submitter
1810288	GRCh37/hg19 16p11.2(chr16:29651706-30193525)x1	SPN	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SFTPA1	Orphanet:2032	Idiopathic pulmonary fibrosis
ALDOA	Orphanet:57	Glycogen storage disease due to aldolase A deficiency
ATP2A1	Orphanet:53347	Brody myopathy

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SFTPA1	HGNC:10798	ENSG00000122852	Q8IWL2	Pulmonary surfactant-associated protein A1	clinvar
SPN	HGNC:11249	ENSG00000197471	P16150	Leukosialin	clinvar
CDIPT	HGNC:1769	ENSG00000103502	O14735	CDP-diacylglycerol–inositol 3-phosphatidyltransferase	clinvar
CDR2	HGNC:1799	ENSG00000140743	Q01850	Cerebellar degeneration-related protein 2	clinvar
NFATC2IP	HGNC:25906	ENSG00000176953	Q8NCF5	NFATC2-interacting protein	clinvar
PAGR1	HGNC:28707	ENSG00000280789	Q9BTK6	PAXIP1-associated glutamate-rich protein 1	clinvar
NPIPB5	HGNC:37233	ENSG00000243716	A8MRT5	Nuclear pore complex-interacting protein family member B5	clinvar
ALDOA	HGNC:414	ENSG00000149925	P04075	Fructose-bisphosphate aldolase A	clinvar
ATP2A1	HGNC:811	ENSG00000196296	O14983	Sarcoplasmic/endoplasmic reticulum calcium ATPase 1	clinvar
PPP1R9B	HGNC:9298	ENSG00000108819	Q96SB3	Neurabin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SFTPA1	Pulmonary surfactant-associated protein A1	In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration.
SPN	Leukosialin	Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration.
CDIPT	CDP-diacylglycerol–inositol 3-phosphatidyltransferase	Catalyzes the biosynthesis of phosphatidylinositol (PtdIns) as well as PtdIns:inositol exchange reaction.
NFATC2IP	NFATC2-interacting protein	In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2.
PAGR1	PAXIP1-associated glutamate-rich protein 1	Its association with the histone methyltransferase MLL2/MLL3 complex is suggesting a role in epigenetic transcriptional activation.
ALDOA	Fructose-bisphosphate aldolase A	Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis.
ATP2A1	Sarcoplasmic/endoplasmic reticulum calcium ATPase 1	Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum.
PPP1R9B	Neurabin-2	Seems to act as a scaffold protein in multiple signaling pathways.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 6 · Druggable fraction: 0.2

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	2.4×	0.701
Scaffold/PPI	1	1.7×	0.701
Other/Unknown	6	1.1×	0.701
Transcription factor	1	0.8×	0.725

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SFTPA1	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
SPN	Other/Unknown	no		Leukosialin
CDIPT	Enzyme (other)	yes	2.7.8.11	CDP-OH_P_trans, CDP_diag_ino_3_P_euk, CDP-OH_PTrfase_TM_dom
CDR2	Other/Unknown	no		CDR2
NFATC2IP	Other/Unknown	no		Ubiquitin-like_dom, Rad60/SUMO-like_dom, Ubiquitin-like_domsf
PAGR1	Other/Unknown	no		PA1
NPIPB5	Other/Unknown	no		NPIP, NPB13-like_MII_rpt, NPIP_N
ALDOA	Enzyme (other)	yes	4.1.2.13	FBA_I, Aldolase_TIM, Aldolase_I_AS
ATP2A1	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIA
PPP1R9B	Scaffold/PPI	no		PDZ, PDZ_sf, Neurabin-1/2_PDZ

Expression context

Cohort genes with no expression data: 0.

9 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right hemisphere of cerebellum	3
granulocyte	2
cerebellar hemisphere	2
hindlimb stylopod muscle	2
lung	1
right lung	1
upper lobe of left lung	1
buccal mucosa cell	1
leukocyte	1
cervix squamous epithelium	1
endothelial cell	1
parotid gland	1
pigmented layer of retina	1
retina	1
secondary oocyte	1
pylorus	1
trabecular bone tissue	1
visceral pleura	1
cerebellar cortex	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SFTPA1	111	tissue_specific	marker	right lung, upper lobe of left lung, lung
SPN	241	broad	marker	buccal mucosa cell, granulocyte, leukocyte
CDIPT	299	ubiquitous	marker	parotid gland, endothelial cell, cervix squamous epithelium
CDR2	255	ubiquitous	yes	secondary oocyte, pigmented layer of retina, retina
NFATC2IP	290	ubiquitous	marker	trabecular bone tissue, pylorus, visceral pleura
PAGR1	229	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
NPIPB5	250	broad	marker	right uterine tube, right hemisphere of cerebellum, cerebellar hemisphere
ALDOA	134	ubiquitous	marker	skeletal muscle tissue, gastrocnemius, hindlimb stylopod muscle
ATP2A1	185	tissue_specific	marker	hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, diaphragm
PPP1R9B	235	ubiquitous	marker	right hemisphere of cerebellum, granulocyte, anterior cingulate cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDOA	3,591
NFATC2IP	3,415
CDIPT	3,399
ATP2A1	2,809
SPN	2,228
PPP1R9B	2,061
CDR2	1,475
PAGR1	748
NPIPB5	692
SFTPA1	12

Structural data

PDB: 2 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALDOA	P04075	8
NFATC2IP	Q8NCF5	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDIPT	O14735	90.02
ATP2A1	O14983	88.65
SFTPA1	Q8IWL2	83.15
CDR2	Q01850	74.84
PAGR1	Q9BTK6	64.26
PPP1R9B	Q96SB3	63.67
SPN	P16150	53.86
NPIPB5	A8MRT5	44.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. Enrichment computed across 10 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Hemostasis	3	18.0×	0.020	SPN, ALDOA, ATP2A1
Diseases associated with surfactant metabolism	1	475.8×	0.036	SFTPA1
Synthesis of PI	1	380.7×	0.036	CDIPT
Defective CSF2RB causes SMDP5	1	271.9×	0.036	SFTPA1
Defective CSF2RA causes SMDP4	1	271.9×	0.036	SFTPA1
Reduction of cytosolic Ca++ levels	1	158.6×	0.046	ATP2A1
Glucose metabolism	1	146.4×	0.046	ALDOA
Platelet calcium homeostasis	1	119.0×	0.046	ATP2A1
Signal regulatory protein family interactions	1	112.0×	0.046	SFTPA1
Pre-NOTCH Processing in Golgi	1	105.7×	0.046	ATP2A1
Regulation of TLR by endogenous ligand	1	82.8×	0.051	SFTPA1
Basigin interactions	1	73.2×	0.051	SPN
Gluconeogenesis	1	73.2×	0.051	ALDOA
Pre-NOTCH Expression and Processing	1	61.4×	0.053	ATP2A1
Surfactant metabolism	1	61.4×	0.053	SFTPA1
Glycerophospholipid biosynthesis	1	56.0×	0.054	CDIPT
Glycolysis	1	47.6×	0.055	ALDOA
Platelet homeostasis	1	46.4×	0.055	ATP2A1
Formation of WDR5-containing histone-modifying complexes	1	44.3×	0.055	PAGR1
Innate Immune System	2	8.5×	0.055	SFTPA1, ALDOA
Ion transport by P-type ATPases	1	34.6×	0.061	ATP2A1
Ion homeostasis	1	34.0×	0.061	ATP2A1
Phospholipid metabolism	1	33.4×	0.061	CDIPT
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	32.8×	0.061	PAGR1
Signaling by NOTCH	1	29.3×	0.063	ATP2A1
Toll Like Receptor 2 (TLR2) Cascade	1	28.8×	0.063	SFTPA1
Toll Like Receptor TLR1:TLR2 Cascade	1	28.0×	0.063	SFTPA1
Response to elevated platelet cytosolic Ca2+	1	27.2×	0.063	ALDOA
Cell-Cell communication	1	22.9×	0.072	SFTPA1
Toll Like Receptor 4 (TLR4) Cascade	1	21.9×	0.073	SFTPA1

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
CDP-diacylglycerol metabolic process	1	2106.5×	0.009	CDIPT
maintenance of mitochondrion location	1	2106.5×	0.009	ATP2A1
negative regulation of type IV hypersensitivity	1	1053.2×	0.009	SPN
positive regulation of fast-twitch skeletal muscle fiber contraction	1	1053.2×	0.009	ATP2A1
positive regulation of ATPase-coupled calcium transmembrane transporter activity	1	1053.2×	0.009	ATP2A1
positive regulation of calcium ion import into sarcoplasmic reticulum	1	1053.2×	0.009	ATP2A1
positive regulation of protein localization to actin cortical patch	1	1053.2×	0.009	PPP1R9B
response to L-phenylalanine derivative	1	1053.2×	0.009	PPP1R9B
response to protozoan	1	702.2×	0.009	SPN
positive regulation of endoplasmic reticulum calcium ion concentration	1	702.2×	0.009	ATP2A1
negative regulation of striated muscle contraction	1	702.2×	0.009	ATP2A1
relaxation of skeletal muscle	1	702.2×	0.009	ATP2A1
positive regulation of cardiac muscle cell contraction	1	702.2×	0.009	ATP2A1
calcium ion import into sarcoplasmic reticulum	1	702.2×	0.009	ATP2A1
protein localization to cell periphery	1	702.2×	0.009	PPP1R9B
regulation of opioid receptor signaling pathway	1	702.2×	0.009	PPP1R9B
regulation of cell growth by extracellular stimulus	1	526.6×	0.010	PPP1R9B
T-helper 1 cell lineage commitment	1	526.6×	0.010	SPN
cellular response to morphine	1	526.6×	0.010	PPP1R9B
actin filament organization	2	29.7×	0.010	ALDOA, PPP1R9B
developmental process involved in reproduction	1	421.3×	0.012	PPP1R9B
negative regulation of endoplasmic reticulum calcium ion concentration	1	351.1×	0.013	ATP2A1
protein localization to actin cytoskeleton	1	351.1×	0.013	PPP1R9B
reproductive system development	1	300.9×	0.013	PPP1R9B
response to kainic acid	1	300.9×	0.013	PPP1R9B
regulation of T cell migration	1	300.9×	0.013	SPN
regulation of striated muscle contraction	1	263.3×	0.013	ATP2A1
fructose 1,6-bisphosphate metabolic process	1	263.3×	0.013	ALDOA
regulation of defense response to virus	1	263.3×	0.013	SPN
male mating behavior	1	263.3×	0.013	PPP1R9B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 9

Druggability breadth: 5 of 10 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALDOA	1	2
SFTPA1	0	0
SPN	0	0
CDIPT	0	0
CDR2	0	0
NFATC2IP	0	0
PAGR1	0	0
NPIPB5	0	0
ATP2A1	0	0
PPP1R9B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ALDOA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
ALDOA	9	Binding:9
ATP2A1	6	Binding:6
PPP1R9B	6	Binding:6
CDIPT	1	Binding:1
CDR2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CDIPT	2.7.8.11	CDP-diacylglycerol-inositol 3-phosphatidyltransferase
ALDOA	4.1.2.13	fructose-bisphosphate aldolase

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	ALDOA

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	1	ALDOA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CDIPT
E	Difficult family or no structure, no drug	8	SFTPA1, SPN, CDR2, NFATC2IP, PAGR1, NPIPB5, ATP2A1, PPP1R9B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SFTPA1	0	—
SPN	0	—
CDIPT	1	—
CDR2	1	—
NFATC2IP	0	—
PAGR1	0	—
NPIPB5	0	—
ATP2A1	6	—
PPP1R9B	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04271332	PHASE2	ACTIVE_NOT_RECRUITING	Safety, Tolerability, and Efficacy of Arbaclofen in 16p11.2 Deletion
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ARBACLOFEN	3	1