DYRK1A-related intellectual disability syndrome

Summary

DYRK1A-related intellectual disability syndrome (MONDO:0013578) is a disease caused by DYRK1A (GenCC Definitive), with 6 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DYRK1A (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 880
• Phenotypes (HPO): 73

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		54	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
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:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0003086	Acromesomelia	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0000733	Abnormal repetitive mannerisms	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001518	Small for gestational age	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0011451	Congenital microcephaly	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000341	Narrow forehead	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000411	Protruding ear	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)
HP:0000483	Astigmatism	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000490	Deeply set eye	Occasional (5-29%)
HP:0000540	Hypermetropia	Occasional (5-29%)
HP:0000543	Optic disc pallor	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000577	Exotropia	Occasional (5-29%)
HP:0000646	Amblyopia	Occasional (5-29%)
HP:0000752	Hyperactivity	Occasional (5-29%)
HP:0001166	Arachnodactyly	Occasional (5-29%)
HP:0001659	Aortic regurgitation	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002120	Cerebral cortical atrophy	Occasional (5-29%)
HP:0002365	Hypoplasia of the brainstem	Occasional (5-29%)
HP:0002719	Recurrent infections	Occasional (5-29%)
HP:0002828	Multiple joint contractures	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0007957	Corneal opacity	Occasional (5-29%)
HP:0010442	Polydactyly	Occasional (5-29%)
HP:0010627	Anterior pituitary hypoplasia	Occasional (5-29%)
HP:0010864	Intellectual disability, severe	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	DYRK1A-related intellectual disability syndrome
Mondo ID	MONDO:0013578
OMIM	614104
Orphanet	464306
DOID	DOID:0070037
UMLS	C5568143
MedGen	1799566
GARD	0013527
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 7 · intellectual disability, autosomal dominant 7 · intellectual disability, autosomal dominant type 7 · mental retardation, autosomal dominant 7 · mental retardation, autosomal dominant type 7 · MRD7

Data availability: 880 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › DYRK1A-related 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, 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, 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

Subtypes (2): DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion, intellectual disability syndrome due to a DYRK1A point mutation

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:

231 likely benign, 180 uncertain significance, 80 pathogenic, 34 benign, 29 conflicting classifications of pathogenicity, 22 likely pathogenic, 13 benign/likely benign, 10 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1015236	NM_001347721.2(DYRK1A):c.833A>G (p.Asp278Gly)	DYRK1A	Pathogenic	criteria provided, single submitter
1068692	NM_001347721.2(DYRK1A):c.763A>T (p.Lys255Ter)	DYRK1A	Pathogenic	criteria provided, single submitter
1073604	NC_000021.8:g.(?38844966)(38845202_?)del	DYRK1A	Pathogenic	criteria provided, single submitter
1073605	NC_000021.8:g.(?38844966)(38884854_?)del	DYRK1A	Pathogenic	criteria provided, single submitter
1076837	NM_001347721.2(DYRK1A):c.331C>T (p.Gln111Ter)	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1162313	NM_001347721.2(DYRK1A):c.924+1G>C	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1162778	NM_001347721.2(DYRK1A):c.772C>T (p.Gln258Ter)	DYRK1A	Pathogenic	criteria provided, single submitter
1254755	NM_001347721.2(DYRK1A):c.1190_1193del (p.Lys397fs)	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1299504	NM_001347721.2(DYRK1A):c.433_439del (p.Lys145fs)	DYRK1A	Pathogenic	criteria provided, single submitter
1320058	NM_001347721.2(DYRK1A):c.637+2dup	DYRK1A	Pathogenic	criteria provided, single submitter
1333385	NM_001347721.2(DYRK1A):c.638-1G>T	DYRK1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343233	NM_001347721.2(DYRK1A):c.827A>G (p.His276Arg)	DYRK1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1374418	NM_001347721.2(DYRK1A):c.748_749del (p.Leu250fs)	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1388377	NM_001347721.2(DYRK1A):c.1699C>T (p.Gln567Ter)	DYRK1A	Pathogenic	criteria provided, single submitter
1396925	NM_001347721.2(DYRK1A):c.293_294dup (p.Asn99fs)	DYRK1A	Pathogenic	criteria provided, single submitter
1425863	NM_001347721.2(DYRK1A):c.1158dup (p.Glu387Ter)	DYRK1A	Pathogenic	criteria provided, single submitter
1436085	NM_001347721.2(DYRK1A):c.210dup (p.Arg71fs)	DYRK1A	Pathogenic	criteria provided, single submitter
1457564	NM_001347721.2(DYRK1A):c.267_268dup (p.Asp90fs)	DYRK1A	Pathogenic	criteria provided, single submitter
162152	NM_001347721.2(DYRK1A):c.736C>T (p.Arg246Ter)	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts
162153	NM_001347721.2(DYRK1A):c.586C>T (p.Arg196Ter)	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts
162158	NM_001347721.2(DYRK1A):c.1282C>T (p.Arg428Ter)	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1685756	NM_001347721.2(DYRK1A):c.638-1G>A	DYRK1A	Pathogenic	criteria provided, single submitter
1691094	NM_001347721.2(DYRK1A):c.848dup (p.Asn283fs)	DYRK1A	Pathogenic	criteria provided, single submitter
1691633	NM_001347721.2(DYRK1A):c.250_251del (p.Leu84fs)	DYRK1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691681	NM_001347721.2(DYRK1A):c.840dup (p.Pro281fs)	DYRK1A	Pathogenic	no assertion criteria provided
1708487	NM_001347721.2(DYRK1A):c.367G>T (p.Glu123Ter)	DYRK1A	Pathogenic	criteria provided, single submitter
1709300	NM_001347721.2(DYRK1A):c.1114_1133del (p.Pro372fs)	DYRK1A	Pathogenic	criteria provided, single submitter
1709937	NM_001347721.2(DYRK1A):c.701dup (p.Tyr234Ter)	DYRK1A	Pathogenic	criteria provided, single submitter
1722317	NM_001347721.2(DYRK1A):c.986dup (p.Tyr329Ter)	DYRK1A	Pathogenic	criteria provided, single submitter
1759288	NM_001347721.2(DYRK1A):c.1218C>G (p.Tyr406Ter)	DYRK1A	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 4 · 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
DYRK1A	Definitive	Autosomal dominant	DYRK1A-related intellectual disability syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DYRK1A	Orphanet:268261	DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion
DYRK1A	Orphanet:464311	Intellectual disability syndrome due to a DYRK1A point mutation
ERG	Orphanet:319	Skeletal Ewing sarcoma
ERG	Orphanet:370334	Extraskeletal Ewing sarcoma

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DYRK1A	HGNC:3091	ENSG00000157540	Q13627	Dual specificity tyrosine-phosphorylation-regulated kinase 1A	gencc,clinvar
TTC3	HGNC:12393	ENSG00000182670	P53804	E3 ubiquitin-protein ligase TTC3	clinvar
CBR1	HGNC:1548	ENSG00000159228	P16152	Carbonyl reductase [NADPH] 1	clinvar
ERG	HGNC:3446	ENSG00000157554	P11308	Transcriptional regulator ERG	clinvar
ETS2	HGNC:3489	ENSG00000157557	P15036	Protein C-ets-2	clinvar
ATP5PO	HGNC:850	ENSG00000241837	P48047	ATP synthase peripheral stalk subunit OSCP, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYRK1A	Dual specificity tyrosine-phosphorylation-regulated kinase 1A	Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities.
TTC3	E3 ubiquitin-protein ligase TTC3	E3 ubiquitin-protein ligase which catalyzes the formation of ‘Lys-48’-polyubiquitin chains.
CBR1	Carbonyl reductase [NADPH] 1	NADPH-dependent reductase with broad substrate specificity.
ERG	Transcriptional regulator ERG	Transcriptional regulator.
ETS2	Protein C-ets-2	Transcription factor activating transcription.
ATP5PO	ATP synthase peripheral stalk subunit OSCP, mitochondrial	Subunit OSCP, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of…

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33

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
Kinase	1	4.6×	0.719
Enzyme (other)	1	2.0×	0.719
Transcription factor	1	1.4×	0.719
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYRK1A	Kinase	yes	2.7.12.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TTC3	Transcription factor	no		Znf_RING, DEATH-like_dom_sf, TPR-like_helical_dom_sf
CBR1	Enzyme (other)	yes	1.1.1.184	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
ERG	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
ETS2	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
ATP5PO	Other/Unknown	no		ATPase_OSCP/dsu, ATPase_OSCP/d_CS, ATP_synth_OSCP/delta_N_sf

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
amniotic fluid	1
biceps brachii	1
cortical plate	1
entorhinal cortex	1
middle temporal gyrus	1
C1 segment of cervical spinal cord	1
duodenum	1
jejunal mucosa	1
descending thoracic aorta	1
tendon of biceps brachii	1
thoracic aorta	1
mucosa of urinary bladder	1
skin of abdomen	1
skin of leg	1
apex of heart	1
heart left ventricle	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYRK1A	294	ubiquitous	marker	amniotic fluid, biceps brachii, Brodmann (1909) area 23
TTC3	295	ubiquitous	marker	cortical plate, entorhinal cortex, middle temporal gyrus
CBR1	281	ubiquitous	marker	jejunal mucosa, duodenum, C1 segment of cervical spinal cord
ERG	247	broad	marker	tendon of biceps brachii, descending thoracic aorta, thoracic aorta
ETS2	287	ubiquitous	marker	skin of abdomen, mucosa of urinary bladder, skin of leg
ATP5PO	149	ubiquitous	marker	heart left ventricle, apex of heart, right atrium auricular region

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DYRK1A	4,909
CBR1	3,942
ATP5PO	3,811
ETS2	2,131
ERG	1,223
TTC3	209

Intra-cohort edges

A	B	Sources
ERG	ETS2	biogrid_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYRK1A	Q13627	91
ATP5PO	P48047	9
ERG	P11308	8
CBR1	P16152	6
ETS2	P15036	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TTC3	P53804	62.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	1	190.3×	0.028	CBR1
Formation of ATP by chemiosmotic coupling	1	142.8×	0.028	ATP5PO
Arachidonate metabolism	1	142.8×	0.028	CBR1
G0 and Early G1	1	109.8×	0.028	DYRK1A
Cristae formation	1	86.5×	0.028	ATP5PO
Oncogene Induced Senescence	1	84.0×	0.028	ETS2
Mitochondrial biogenesis	1	42.0×	0.047	ATP5PO
Fatty acid metabolism	1	32.8×	0.053	CBR1
Mitochondrial protein degradation	1	28.6×	0.054	ATP5PO
Metabolism	2	5.8×	0.055	CBR1, ATP5PO
Aerobic respiration and respiratory electron transport	1	22.1×	0.057	ATP5PO
Organelle biogenesis and maintenance	1	16.5×	0.069	ATP5PO
Metabolism of lipids	1	7.9×	0.130	CBR1
Metabolism of proteins	1	3.1×	0.286	ATP5PO

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ectodermal cell fate commitment	1	1404.3×	0.009	ETS2
negative regulation of heterochromatin formation	1	1404.3×	0.009	DYRK1A
regulation of amyloid-beta formation	1	1404.3×	0.009	DYRK1A
regulation of neurofibrillary tangle assembly	1	936.2×	0.010	DYRK1A
glucocorticoid metabolic process	1	468.1×	0.014	CBR1
prostanoid biosynthetic process	1	401.2×	0.014	CBR1
vitamin K metabolic process	1	351.1×	0.014	CBR1
protein phosphorylation	2	22.6×	0.014	DYRK1A, ERG
primitive streak formation	1	234.1×	0.017	ETS2
negative regulation of microtubule polymerization	1	216.1×	0.017	DYRK1A
negative regulation of DNA damage response, signal transduction by p53 class mediator	1	187.2×	0.017	DYRK1A
positive regulation of RNA splicing	1	175.5×	0.017	DYRK1A
ATP biosynthetic process	1	165.2×	0.017	ATP5PO
proton motive force-driven ATP synthesis	1	133.8×	0.019	ATP5PO
negative regulation of mRNA splicing, via spliceosome	1	127.7×	0.019	DYRK1A
cellular response to cytokine stimulus	1	90.6×	0.024	ATP5PO
mesoderm development	1	87.8×	0.024	ETS2
positive regulation of reactive oxygen species metabolic process	1	85.1×	0.024	CBR1
peptidyl-tyrosine phosphorylation	1	70.2×	0.028	DYRK1A
cell differentiation	2	9.7×	0.030	ERG, ETS2
proton transmembrane transport	1	52.0×	0.034	ATP5PO
cellular response to cAMP	1	48.4×	0.034	ATP5PO
proton motive force-driven mitochondrial ATP synthesis	1	43.9×	0.036	ATP5PO
regulation of alternative mRNA splicing, via spliceosome	1	40.7×	0.036	DYRK1A
circadian rhythm	1	40.7×	0.036	DYRK1A
epithelial cell differentiation	1	29.3×	0.048	CBR1
protein K48-linked ubiquitination	1	28.1×	0.048	TTC3
xenobiotic metabolic process	1	24.9×	0.052	CBR1
protein autophosphorylation	1	24.2×	0.052	DYRK1A
skeletal system development	1	21.0×	0.058	ETS2

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 6 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
DYRK1A	NIRAPARIB
CBR1	TRICLOSAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DYRK1A	48	4
CBR1	1	4
TTC3	0	0
ERG	0	0
ETS2	0	0
ATP5PO	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIRAPARIB	4	DYRK1A
RUCAPARIB	4	DYRK1A
AFATINIB	4	DYRK1A
RUXOLITINIB	4	DYRK1A
PALBOCICLIB	4	DYRK1A
BELUMOSUDIL	4	DYRK1A
AFATINIB DIMALEATE	4	DYRK1A
ABEMACICLIB	4	DYRK1A
TOVORAFENIB	4	DYRK1A
SUNITINIB	4	DYRK1A
MIDOSTAURIN	4	DYRK1A
TRICLOSAN	4	CBR1
CURCUMIN	3	DYRK1A
CRENOLANIB	3	DYRK1A
EPIGALOCATECHIN GALLATE	3	DYRK1A
ENZASTAURIN	3	DYRK1A
DEFACTINIB	3	DYRK1A
CANERTINIB	3	DYRK1A
BARASERTIB	3	DYRK1A
ALVOCIDIB	3	DYRK1A
LORECIVIVINT	3	DYRK1A
LESTAURTINIB	3	DYRK1A
RUBOXISTAURIN	3	DYRK1A
SILMITASERTIB	2	DYRK1A
SELICICLIB	2	DYRK1A
CC-401	2	DYRK1A
SU-014813	2	DYRK1A
ZOTIRACICLIB	2	DYRK1A
TG100-115	2	DYRK1A
UPROSERTIB	2	DYRK1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
DYRK1A	866	Binding:855, Functional:7, ADMET:4
CBR1	35	Binding:28, ADMET:7
ERG	14	Binding:10, Functional:3, ADMET:1
ATP5PO	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DYRK1A	2.7.12.1	dual-specificity kinase
CBR1	1.1.1.184	carbonyl reductase (NADPH)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
DYRK1A	866

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
NIRAPARIB	4	DYRK1A
RUCAPARIB	4	DYRK1A
AFATINIB	4	DYRK1A
RUXOLITINIB	4	DYRK1A
PALBOCICLIB	4	DYRK1A
BELUMOSUDIL	4	DYRK1A
AFATINIB DIMALEATE	4	DYRK1A
ABEMACICLIB	4	DYRK1A
TOVORAFENIB	4	DYRK1A
SUNITINIB	4	DYRK1A
MIDOSTAURIN	4	DYRK1A
TRICLOSAN	4	CBR1
CURCUMIN	3	DYRK1A
CRENOLANIB	3	DYRK1A
EPIGALOCATECHIN GALLATE	3	DYRK1A
ENZASTAURIN	3	DYRK1A
DEFACTINIB	3	DYRK1A
CANERTINIB	3	DYRK1A
BARASERTIB	3	DYRK1A
ALVOCIDIB	3	DYRK1A
LORECIVIVINT	3	DYRK1A
LESTAURTINIB	3	DYRK1A
RUBOXISTAURIN	3	DYRK1A
SILMITASERTIB	2	DYRK1A
SELICICLIB	2	DYRK1A
CC-401	2	DYRK1A
SU-014813	2	DYRK1A
ZOTIRACICLIB	2	DYRK1A
TG100-115	2	DYRK1A
UPROSERTIB	2	DYRK1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	DYRK1A, CBR1
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	4	TTC3, ERG, ETS2, ATP5PO

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TTC3	0	—
ERG	14	—
ETS2	0	—
ATP5PO	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.