Bohring-Opitz syndrome

Summary

Bohring-Opitz syndrome (MONDO:0011510) is a disease caused by ASXL1 (GenCC Definitive), with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ASXL1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 172
• Phenotypes (HPO): 65
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		46	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001052	Nevus flammeus	Very frequent (80-99%)
HP:0012758	Neurodevelopmental delay	Very frequent (80-99%)
HP:0000243	Trigonocephaly	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000293	Full cheeks	Frequent (30-79%)
HP:0000297	Facial hypotonia	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0000589	Coloboma	Frequent (30-79%)
HP:0000648	Optic atrophy	Frequent (30-79%)
HP:0000664	Synophrys	Frequent (30-79%)
HP:0000998	Hypertrichosis	Frequent (30-79%)
HP:0001105	Retinal atrophy	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001376	Limitation of joint mobility	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001525	Severe failure to thrive	Frequent (30-79%)
HP:0001662	Bradycardia	Frequent (30-79%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002104	Apnea	Frequent (30-79%)
HP:0002187	Intellectual disability, profound	Frequent (30-79%)
HP:0002205	Recurrent respiratory infections	Frequent (30-79%)
HP:0002360	Sleep abnormality	Frequent (30-79%)
HP:0002540	Inability to walk	Frequent (30-79%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0002803	Congenital contracture	Frequent (30-79%)
HP:0002870	Obstructive sleep apnea	Frequent (30-79%)
HP:0003049	Ulnar deviation of the wrist	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0005487	Prominent metopic ridge	Frequent (30-79%)
HP:0006471	Fixed elbow flexion	Frequent (30-79%)
HP:0006863	Severe expressive language delay	Frequent (30-79%)
HP:0006895	Lower limb hypertonia	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0008936	Axial hypotonia	Frequent (30-79%)
HP:0010733	Naevus flammeus of the eyelid	Frequent (30-79%)
HP:0010864	Intellectual disability, severe	Frequent (30-79%)
HP:0012537	Food intolerance	Frequent (30-79%)
HP:0040082	Happy demeanor	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Occasional (5-29%)
HP:0000016	Urinary retention	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000278	Retrognathia	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000431	Wide nasal bridge	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001305	Dandy-Walker malformation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Bohring-Opitz syndrome
Mondo ID	MONDO:0011510
MeSH	C537419
OMIM	605039
Orphanet	97297
NCIT	C131533
SNOMED CT	720565000
UMLS	C0796232
MedGen	208678
GARD	0010140
NORD	1981
Is cancer (heuristic)	no

Also known as: Bohring syndrome · Bohring-Opitz syndrome · BOPS · Bos syndrome · C-like syndrome · Oberklaid-Danks syndrome · Opitz trigonocephaly-like syndrome

Data availability: 172 ClinVar variants · 6 GenCC gene-disease records.

Disease family

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

172 retrieved; paginated sample, class counts are floors:

44 pathogenic, 38 benign/likely benign, 32 uncertain significance, 26 likely pathogenic, 17 benign, 8 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031902	NM_015338.6(ASXL1):c.3437C>A (p.Ser1146Ter)	ASXL1	Pathogenic	criteria provided, single submitter
1174493	NM_015338.6(ASXL1):c.1719+1G>A	ASXL1	Pathogenic	no assertion criteria provided
1188832	NM_015338.6(ASXL1):c.2759_2762dup (p.Val922fs)	ASXL1	Pathogenic	no assertion criteria provided
1701085	NM_015338.6(ASXL1):c.1720A>G (p.Ile574Val)	ASXL1	Pathogenic	no assertion criteria provided
1727002	NM_015338.6(ASXL1):c.1436_1437del (p.Pro479fs)	ASXL1	Pathogenic	no assertion criteria provided
1803980	NM_015338.6(ASXL1):c.3942_3957del (p.Gln1315fs)	ASXL1	Pathogenic	criteria provided, single submitter
2499575	NM_015338.6(ASXL1):c.1368_1371del (p.Asp457fs)	ASXL1	Pathogenic	criteria provided, single submitter
2500280	NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs)	ASXL1	Pathogenic	criteria provided, single submitter
2664081	NM_015338.6(ASXL1):c.2302dup (p.Gln768fs)	ASXL1	Pathogenic	criteria provided, single submitter
280228	NM_015338.6(ASXL1):c.1867C>T (p.Gln623Ter)	ASXL1	Pathogenic	criteria provided, multiple submitters, no conflicts
280245	NM_015338.6(ASXL1):c.1544_1545del (p.Val515fs)	ASXL1	Pathogenic	criteria provided, multiple submitters, no conflicts
280841	NM_015338.6(ASXL1):c.1282C>T (p.Gln428Ter)	ASXL1	Pathogenic	criteria provided, multiple submitters, no conflicts
288745	NM_015338.6(ASXL1):c.1162_1163del (p.Val388fs)	ASXL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3062120	NM_015338.6(ASXL1):c.2456del (p.Gly819fs)	ASXL1	Pathogenic	criteria provided, single submitter
3062126	NM_015338.6(ASXL1):c.2789G>A (p.Trp930Ter)	ASXL1	Pathogenic	criteria provided, single submitter
3066302	NM_015338.6(ASXL1):c.1109C>G (p.Ser370Ter)	ASXL1	Pathogenic	criteria provided, single submitter
3069100	NM_015338.6(ASXL1):c.2644C>T (p.Gln882Ter)	ASXL1	Pathogenic	criteria provided, single submitter
3075707	NM_015338.6(ASXL1):c.2461dup (p.Asp821fs)	ASXL1	Pathogenic	criteria provided, single submitter
30985	NM_015338.6(ASXL1):c.2773C>T (p.Gln925Ter)	ASXL1	Pathogenic	criteria provided, single submitter
30986	NM_015338.6(ASXL1):c.1210C>T (p.Arg404Ter)	ASXL1	Pathogenic	criteria provided, multiple submitters, no conflicts
30987	NM_015338.6(ASXL1):c.3083C>A (p.Ser1028Ter)	ASXL1	Pathogenic	no assertion criteria provided
30988	NM_015338.6(ASXL1):c.2535dup (p.Ser846fs)	ASXL1	Pathogenic	criteria provided, single submitter
30989	NM_015338.6(ASXL1):c.2197C>T (p.Gln733Ter)	ASXL1	Pathogenic	criteria provided, single submitter
3254708	NM_015338.6(ASXL1):c.2929C>T (p.Gln977Ter)	ASXL1	Pathogenic	criteria provided, single submitter
3254959	NM_015338.6(ASXL1):c.2367_2368del (p.Cys789_Glu790delinsTer)	ASXL1	Pathogenic	criteria provided, single submitter
3335981	NM_015338.6(ASXL1):c.2982del (p.His995fs)	ASXL1	Pathogenic	criteria provided, single submitter
3391152	NM_015338.6(ASXL1):c.472-2A>G	ASXL1	Pathogenic	criteria provided, multiple submitters, no conflicts
3778643	NM_015338.6(ASXL1):c.374-1G>A	ASXL1	Pathogenic	no assertion criteria provided
3778658	NM_015338.6(ASXL1):c.1091del (p.Gly364fs)	ASXL1	Pathogenic	criteria provided, single submitter
3895921	NM_015338.6(ASXL1):c.1636C>T (p.Gln546Ter)	ASXL1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 10 · 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
ASXL1	Definitive	Autosomal dominant	Bohring-Opitz syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ASXL1	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
ASXL1	Orphanet:97297	Bohring-Opitz syndrome
ASXL1	Orphanet:98823	Chronic myelomonocytic leukemia
ASXL1	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
ASXL1	Orphanet:98850	Aggressive systemic mastocytosis
KLHL7	Orphanet:157820	Cold-induced sweating syndrome
KLHL7	Orphanet:603684	KLHL7-related Bohring-Opitz-like and Crisponi/Cold-induced sweating-like overlap syndrome
KLHL7	Orphanet:603689	KLHL7-related Bohring-Opitz-like syndrome
KLHL7	Orphanet:603694	KLHL7-related Crisponi/cold-induced sweating-like syndrome
KLHL7	Orphanet:791	Retinitis pigmentosa

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
ASXL1	HGNC:18318	ENSG00000171456	Q8IXJ9	Polycomb group protein ASXL1	gencc,clinvar
KLHL7	HGNC:15646	ENSG00000122550	Q8IXQ5	Kelch-like protein 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ASXL1	Polycomb group protein ASXL1	Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG).
KLHL7	Kelch-like protein 7	Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ASXL1	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
KLHL7	Other/Unknown	no		BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf

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
adrenal tissue	1
sperm	1
sural nerve	1
heart right ventricle	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ASXL1	294	ubiquitous	marker	sural nerve, sperm, adrenal tissue
KLHL7	274	ubiquitous	marker	oocyte, secondary oocyte, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASXL1	2,816
KLHL7	1,123

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASXL1	Q8IXJ9	4
KLHL7	Q8IXQ5	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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
Deubiquitination	1	124.1×	0.016	ASXL1
UCH proteinases	1	124.1×	0.016	ASXL1
Post-translational protein modification	1	19.2×	0.069	ASXL1
Metabolism of proteins	1	12.4×	0.081	ASXL1

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
regulation of kidney size	1	4213.0×	0.004	ASXL1
positive regulation of retinoic acid receptor signaling pathway	1	1685.2×	0.004	ASXL1
negative regulation of peroxisome proliferator activated receptor signaling pathway	1	1404.3×	0.004	ASXL1
lung saccule development	1	1053.2×	0.004	ASXL1
bone marrow development	1	766.0×	0.004	ASXL1
podocyte development	1	766.0×	0.004	ASXL1
homeostasis of number of cells	1	337.0×	0.008	ASXL1
response to retinoic acid	1	191.5×	0.010	ASXL1
heart morphogenesis	1	187.2×	0.010	ASXL1
thymus development	1	168.5×	0.010	ASXL1
negative regulation of fat cell differentiation	1	156.0×	0.010	ASXL1
hemopoiesis	1	133.8×	0.011	ASXL1
animal organ morphogenesis	1	95.8×	0.014	ASXL1
cell morphogenesis	1	78.8×	0.016	ASXL1
chromatin organization	1	49.6×	0.024	ASXL1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	26.1×	0.043	KLHL7
protein ubiquitination	1	20.7×	0.051	KLHL7
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	ASXL1

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
ASXL1	0	0
KLHL7	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
KLHL7	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ASXL1, KLHL7

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)
ASXL1	0	—
KLHL7	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03303716	Not specified	RECRUITING	ASXL-Related Disorders Natural History Study