Schuurs-Hoeijmakers syndrome

Summary

Schuurs-Hoeijmakers syndrome (MONDO:0014006) is a disease caused by PACS1 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PACS1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 758
• Phenotypes (HPO): 59
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000411	Protruding ear	Frequent (30-79%)
HP:0000414	Bulbous nose	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000527	Long eyelashes	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001488	Bilateral ptosis	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002553	Highly arched eyebrow	Frequent (30-79%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0012443	Abnormality of brain morphology	Frequent (30-79%)
HP:0012523	Oral aversion	Frequent (30-79%)
HP:0025160	Abnormal temper tantrums	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000154	Wide mouth	Occasional (5-29%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000294	Low anterior hairline	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000589	Coloboma	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)
HP:0000699	Diastema	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0000954	Single transverse palmar crease	Occasional (5-29%)
HP:0001195	Single umbilical artery	Occasional (5-29%)
HP:0001238	Slender finger	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001321	Cerebellar hypoplasia	Occasional (5-29%)
HP:0001344	Absent speech	Occasional (5-29%)
HP:0001537	Umbilical hernia	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001647	Bicuspid aortic valve	Occasional (5-29%)
HP:0001655	Patent foramen ovale	Occasional (5-29%)
HP:0001763	Pes planus	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002317	Unsteady gait	Occasional (5-29%)
HP:0002389	Cavum septum pellucidum	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Schuurs-Hoeijmakers syndrome
Mondo ID	MONDO:0014006
OMIM	615009
Orphanet	329224
DOID	DOID:0070047
NCIT	C150555
UMLS	C3554343
MedGen	767257
GARD	0013043
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 17 · autosomal dominant intellectual disability-17 · intellectual disability, autosomal dominant 17 · intellectual disability, autosomal dominant type 17 · intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome · mental retardation, autosomal dominant 17 · mental retardation, autosomal dominant type 17 · MRD17 · PACS1-related syndrome · Schuurs-Hoeijmakers syndrome · SHMS

Data availability: 758 ClinVar variants · 5 GenCC gene-disease records · 9 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Schuurs-Hoeijmakers syndrome

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

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

600 retrieved; paginated sample, class counts are floors:

308 likely benign, 182 uncertain significance, 45 benign, 41 conflicting classifications of pathogenicity, 22 benign/likely benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686002	NM_018026.4(PACS1):c.1574G>A (p.Arg525Lys)	PACS1	Pathogenic	criteria provided, single submitter
1802617	NM_018026.4(PACS1):c.298C>T (p.Gln100Ter)	LOC130006099	Likely pathogenic	criteria provided, single submitter
1012800	NM_018026.4(PACS1):c.1495G>A (p.Val499Met)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032016	NM_018026.4(PACS1):c.661-15T>A	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1098662	NM_018026.4(PACS1):c.2281C>A (p.Pro761Thr)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1184327	NM_018026.4(PACS1):c.104AGC[9] (p.Gln38_Gln40dup)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1186528	NM_018026.4(PACS1):c.1516C>T (p.Arg506Trp)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1187803	NM_018026.4(PACS1):c.1079G>A (p.Arg360Gln)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1191641	NM_018026.4(PACS1):c.1838+3A>G	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1201378	NM_018026.4(PACS1):c.1412C>T (p.Thr471Met)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1204818	NM_018026.4(PACS1):c.2087C>T (p.Ser696Leu)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1205017	NM_018026.4(PACS1):c.401T>C (p.Met134Thr)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1217779	NM_018026.4(PACS1):c.1760G>A (p.Arg587Gln)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1300870	NM_018026.4(PACS1):c.2450G>C (p.Gly817Ala)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1301252	NM_018026.4(PACS1):c.2327C>G (p.Thr776Ser)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1314066	NM_018026.4(PACS1):c.1588G>A (p.Asp530Asn)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1321822	NM_018026.4(PACS1):c.2413G>A (p.Ala805Thr)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1335074	NM_018026.4(PACS1):c.1442C>T (p.Thr481Ile)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1336702	NM_018026.4(PACS1):c.460C>A (p.Leu154Ile)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1341823	NM_018026.4(PACS1):c.1286C>G (p.Thr429Ser)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1450967	NM_018026.4(PACS1):c.676A>C (p.Asn226His)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1490704	NM_018026.4(PACS1):c.2299G>A (p.Gly767Arg)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1511182	NM_018026.4(PACS1):c.712G>A (p.Val238Met)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1517773	NM_018026.4(PACS1):c.2296G>A (p.Asp766Asn)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1696572	NM_018026.4(PACS1):c.2305G>A (p.Asp769Asn)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1704582	NM_018026.4(PACS1):c.357-4C>T	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1900770	NM_018026.4(PACS1):c.943C>T (p.Arg315Trp)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2056834	NM_018026.4(PACS1):c.1238C>T (p.Thr413Met)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2090787	NM_018026.4(PACS1):c.444+9G>A	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211813	NM_018026.4(PACS1):c.1803C>T (p.Ala601=)	PACS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
PACS1	Definitive	Autosomal dominant	Schuurs-Hoeijmakers syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PACS1	Orphanet:329224	Schuurs-Hoeijmakers syndrome

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
PACS1	HGNC:30032	ENSG00000175115	Q6VY07	Phosphofurin acidic cluster sorting protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PACS1	Phosphofurin acidic cluster sorting protein 1	Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PACS1	Other/Unknown	no		PACS1/2_C, PACS1/2_N

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
cortical plate	1
granulocyte	1
minor salivary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PACS1	262	ubiquitous	marker	cortical plate, minor salivary gland, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PACS1	1,091

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PACS1	Q6VY07	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Nef mediated downregulation of MHC class I complex cell surface expression	1	1142.0×	9e-04	PACS1

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
lymphocyte homeostasis	1	1872.4×	0.002	PACS1
protein localization to Golgi apparatus	1	802.5×	0.002	PACS1
protein localization to plasma membrane	1	108.7×	0.009	PACS1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PACS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PACS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PACS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07474298	PHASE1/PHASE2	NOT_YET_RECRUITING	Personalized Antisense Oligonucleotide for A Single Participant With PACS1 Gene Mutation Associated With Schuurs-Hoeijmakers Syndrome (SHMS)