Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome

Summary

Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome (MONDO:0014892) is a disease caused by TRIO (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TRIO (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 211
• Phenotypes (HPO): 55

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001256	Intellectual disability, mild	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002465	Poor speech	Very frequent (80-99%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000324	Facial asymmetry	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000664	Synophrys	Frequent (30-79%)
HP:0000678	Dental crowding	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0001182	Tapered finger	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0004691	2-3 toe syndactyly	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0011451	Congenital microcephaly	Frequent (30-79%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000646	Amblyopia	Occasional (5-29%)
HP:0000706	Unerupted tooth	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000722	Compulsive behaviors	Occasional (5-29%)
HP:0000733	Abnormal repetitive mannerisms	Occasional (5-29%)
HP:0000742	Self-mutilation	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0001155	Abnormality of the hand	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001344	Absent speech	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001674	Complete atrioventricular canal defect	Occasional (5-29%)
HP:0001763	Pes planus	Occasional (5-29%)
HP:0002033	Poor suck	Occasional (5-29%)
HP:0002066	Gait ataxia	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0003072	Hypercalcemia	Occasional (5-29%)
HP:0003196	Short nose	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0004279	Short palm	Occasional (5-29%)
HP:0005484	Secondary microcephaly	Occasional (5-29%)
HP:0006889	Intellectual disability, borderline	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0007970	Congenital ptosis	Occasional (5-29%)
HP:0009659	Partial absence of thumb	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
Mondo ID	MONDO:0014892
OMIM	617061
Orphanet	476126
DOID	DOID:0070074
UMLS	C4310740
MedGen	934707
GARD	0017850
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 44 · intellectual developmental disorder, autosomal dominant 44, with microcephaly · MEBAS · mental retardation, autosomal dominant 44 · mercer-Ba syndrome · MRD44

Data availability: 211 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability 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, Schuurs-Hoeijmakers syndrome, 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, 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

211 retrieved; paginated sample, class counts are floors:

111 uncertain significance, 37 likely pathogenic, 23 pathogenic, 13 benign, 11 conflicting classifications of pathogenicity, 10 pathogenic/likely pathogenic, 5 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2579279	GRCh38/hg38 5p15.33-15.2(chr5:9999-14320000)x1	ADAMTS16	Pathogenic	criteria provided, single submitter
936994	NM_007118.4(TRIO):c.8119C>T (p.Arg2707Ter)	LOC126807323	Pathogenic	criteria provided, single submitter
1683784	NM_007118.4(TRIO):c.838C>T (p.Gln280Ter)	TRIO	Pathogenic	criteria provided, multiple submitters, no conflicts
1694452	NM_007118.4(TRIO):c.4382C>G (p.Pro1461Arg)	TRIO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1707513	NM_007118.4(TRIO):c.5491_5496+12del	TRIO	Pathogenic	criteria provided, single submitter
253080	NM_007118.4(TRIO):c.4128G>A (p.Trp1376Ter)	TRIO	Pathogenic	no assertion criteria provided
253081	NM_007118.4(TRIO):c.3752del (p.Asp1251fs)	TRIO	Pathogenic	no assertion criteria provided
253082	NM_007118.4(TRIO):c.649A>T (p.Arg217Ter)	TRIO	Pathogenic	no assertion criteria provided
253083	NM_007118.4(TRIO):c.4466del (p.Gln1489fs)	TRIO	Pathogenic	no assertion criteria provided
253084	NM_007118.4(TRIO):c.4283G>A (p.Arg1428Gln)	TRIO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253085	NM_007118.4(TRIO):c.4381C>A (p.Pro1461Thr)	TRIO	Pathogenic	criteria provided, single submitter
253086	NM_007118.4(TRIO):c.3239A>T (p.Asn1080Ile)	TRIO	Pathogenic	criteria provided, single submitter
3236236	NM_007118.4(TRIO):c.7048_7051del (p.Pro2350fs)	TRIO	Pathogenic	criteria provided, single submitter
3366985	NM_007118.4(TRIO):c.4231C>T (p.Arg1411Ter)	TRIO	Pathogenic	criteria provided, multiple submitters, no conflicts
3572895	NM_007118.4(TRIO):c.1732-1G>C	TRIO	Pathogenic	criteria provided, single submitter
369657	NM_007118.4(TRIO):c.634G>T (p.Glu212Ter)	TRIO	Pathogenic	criteria provided, single submitter
4072020	NM_007118.4(TRIO):c.4058+1G>A	TRIO	Pathogenic	criteria provided, single submitter
4082031	NM_007118.4(TRIO):c.1422del (p.Ser475fs)	TRIO	Pathogenic	no assertion criteria provided
449111	NM_007118.4(TRIO):c.3232C>T (p.Arg1078Trp)	TRIO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4538184	NM_007118.4(TRIO):c.1714C>T (p.Gln572Ter)	TRIO	Pathogenic	criteria provided, single submitter
4688537	NM_007118.4(TRIO):c.5770del (p.Glu1924fs)	TRIO	Pathogenic	criteria provided, single submitter
4813771	NM_007118.4(TRIO):c.6218C>G (p.Ser2073Ter)	TRIO	Pathogenic	criteria provided, single submitter
504184	NM_007118.4(TRIO):c.3657dup (p.Cys1220fs)	TRIO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545083	NM_007118.4(TRIO):c.4406A>G (p.His1469Arg)	TRIO	Pathogenic	criteria provided, single submitter
830227	NM_007118.4(TRIO):c.3233G>A (p.Arg1078Gln)	TRIO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
830228	NM_007118.4(TRIO):c.3895G>A (p.Glu1299Lys)	TRIO	Pathogenic	criteria provided, single submitter
830230	NM_007118.4(TRIO):c.6092dup (p.Leu2031fs)	TRIO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
873429	NM_007118.4(TRIO):c.298del (p.Arg100fs)	TRIO	Pathogenic	criteria provided, single submitter
975627	NM_007118.4(TRIO):c.5203+1_5203+2dup	TRIO	Pathogenic	no assertion criteria provided
976095	NM_007118.4(TRIO):c.6153+1G>A	TRIO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
TRIO	Definitive	Autosomal dominant	syndromic intellectual disability	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRIO	Orphanet:476126	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRIO	HGNC:12303	ENSG00000038382	O75962	Triple functional domain protein	gencc,clinvar
ADAMTS16	HGNC:17108	ENSG00000145536	Q8TE57	A disintegrin and metalloproteinase with thrombospondin motifs 16	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIO	Triple functional domain protein	Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases.

Protein-family classification

Druggable: 2 · 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
Protease	1	18.3×	0.071
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRIO	Kinase	yes		DH_dom, Prot_kinase_dom, CRAL-TRIO_dom
ADAMTS16	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
stromal cell of endometrium	1
sural nerve	1
buccal mucosa cell	1
left ovary	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIO	279	ubiquitous	marker	sural nerve, cortical plate, stromal cell of endometrium
ADAMTS16	135	broad	marker	buccal mucosa cell, tendon of biceps brachii, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRIO	2,892
ADAMTS16	692

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRIO	O75962	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAMTS16	Q8TE57	72.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DCC mediated attractive signaling	1	356.9×	0.029	TRIO
Defective B3GALTL causes PpS	1	154.3×	0.029	ADAMTS16
O-glycosylation of TSR domain-containing proteins	1	150.3×	0.029	ADAMTS16
Diseases associated with O-glycosylation of proteins	1	107.7×	0.029	ADAMTS16
RHOJ GTPase cycle	1	100.2×	0.029	TRIO
NRAGE signals death through JNK	1	92.1×	0.029	TRIO
RHOG GTPase cycle	1	74.2×	0.029	TRIO
O-linked glycosylation	1	72.3×	0.029	ADAMTS16
G alpha (12/13) signalling events	1	68.8×	0.029	TRIO
Diseases of glycosylation	1	65.6×	0.029	ADAMTS16
RAC2 GTPase cycle	1	63.4×	0.029	TRIO
RAC3 GTPase cycle	1	59.5×	0.029	TRIO
Degradation of the extracellular matrix	1	58.9×	0.029	ADAMTS16
Diseases of metabolism	1	40.2×	0.038	ADAMTS16
RHOA GTPase cycle	1	37.3×	0.038	TRIO
CDC42 GTPase cycle	1	36.1×	0.038	TRIO
Extracellular matrix organization	1	31.6×	0.040	ADAMTS16
RAC1 GTPase cycle	1	30.5×	0.040	TRIO
G alpha (q) signalling events	1	28.7×	0.040	TRIO
Post-translational protein modification	1	9.6×	0.112	ADAMTS16
Disease	1	6.5×	0.154	ADAMTS16
Metabolism of proteins	1	6.2×	0.155	ADAMTS16

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
male gamete generation	1	2106.5×	0.006	ADAMTS16
cell surface receptor protein tyrosine phosphatase signaling pathway	1	1053.2×	0.006	TRIO
regulation of systemic arterial blood pressure	1	526.6×	0.008	ADAMTS16
postsynaptic modulation of chemical synaptic transmission	1	337.0×	0.008	TRIO
regulation of cilium assembly	1	300.9×	0.008	ADAMTS16
branching involved in ureteric bud morphogenesis	1	183.2×	0.011	ADAMTS16
negative regulation of fat cell differentiation	1	156.0×	0.011	TRIO
neuron projection morphogenesis	1	138.1×	0.011	TRIO
regulation of small GTPase mediated signal transduction	1	72.0×	0.018	TRIO
extracellular matrix organization	1	61.1×	0.020	ADAMTS16
axon guidance	1	45.3×	0.024	TRIO
proteolysis	1	17.1×	0.058	ADAMTS16

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 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
TRIO	0	0
ADAMTS16	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TRIO	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	TRIO
D	Druggable family + AlphaFold only, no drug	1	ADAMTS16
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TRIO	2	—
ADAMTS16	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.