Pierpont syndrome

Summary

Pierpont syndrome (MONDO:0011213) is a disease caused by TBL1XR1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TBL1XR1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 469
• Phenotypes (HPO): 48

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

48 HPO clinical features (Orphanet curated; top 48 by frequency):

HPO ID	Term	Frequency
HP:0000232	Everted lower lip vermilion	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000687	Widely spaced teeth	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001763	Pes planus	Very frequent (80-99%)
HP:0006191	Deep palmar crease	Very frequent (80-99%)
HP:0007552	Abnormal subcutaneous fat tissue distribution	Very frequent (80-99%)
HP:0012811	Wide nasal ridge	Very frequent (80-99%)
HP:0045025	Narrow palpebral fissure	Very frequent (80-99%)
HP:0000233	Thin vermilion border	Frequent (30-79%)
HP:0000248	Brachycephaly	Frequent (30-79%)
HP:0000289	Broad philtrum	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000319	Smooth philtrum	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000490	Deeply set eye	Frequent (30-79%)
HP:0000506	Telecanthus	Frequent (30-79%)
HP:0001212	Prominent fingertip pads	Frequent (30-79%)
HP:0001518	Small for gestational age	Frequent (30-79%)
HP:0001831	Short toe	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0006610	Wide intermamillary distance	Frequent (30-79%)
HP:0007367	Atrophy/Degeneration affecting the central nervous system	Frequent (30-79%)
HP:0007605	Excessive wrinkling of palmar skin	Frequent (30-79%)
HP:0009381	Short finger	Frequent (30-79%)
HP:0009909	Uplifted earlobe	Frequent (30-79%)
HP:0011341	Long upper lip	Frequent (30-79%)
HP:0011451	Congenital microcephaly	Frequent (30-79%)
HP:0100872	Abnormality of the plantar skin of foot	Frequent (30-79%)
HP:0410263	Brain imaging abnormality	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000272	Malar flattening	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000482	Microcornea	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0001344	Absent speech	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002308	Chiari malformation	Occasional (5-29%)
HP:0002536	Abnormal cortical gyration	Occasional (5-29%)
HP:0009890	High anterior hairline	Occasional (5-29%)
HP:0011344	Severe global developmental delay	Occasional (5-29%)
HP:0012043	Pendular nystagmus	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Pierpont syndrome
Mondo ID	MONDO:0011213
MeSH	C566559
OMIM	602342
Orphanet	487825
DOID	DOID:0081362
UMLS	C1865644
MedGen	356049
GARD	0017885
Is cancer (heuristic)	no

Also known as: Pierpont syndrome · plantar lipomatosis-facial dysmorphism-developmental delay syndrome · plantar lipomatosis-unusual facies-developmental delay syndrome · PRPTS

Data availability: 469 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 › Pierpont 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, 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, 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

469 retrieved; paginated sample, class counts are floors:

230 likely benign, 157 uncertain significance, 18 likely pathogenic, 17 conflicting classifications of pathogenicity, 15 pathogenic, 15 benign, 8 pathogenic/likely pathogenic, 8 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1076725	NM_024665.7(TBL1XR1):c.1071G>A (p.Trp357Ter)	LOC126806878	Pathogenic	criteria provided, single submitter
2500267	NM_024665.7(TBL1XR1):c.1047+1G>C	LOC126806878	Pathogenic	no assertion criteria provided
372701	NM_024665.7(TBL1XR1):c.1108G>A (p.Asp370Asn)	LOC126806878	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
392060	NM_024665.7(TBL1XR1):c.987G>A (p.Met329Ile)	LOC126806878	Pathogenic	criteria provided, single submitter
666258	NM_024665.7(TBL1XR1):c.1000T>C (p.Cys334Arg)	LOC126806878	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1018524	NM_024665.7(TBL1XR1):c.205-7A>G	TBL1XR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452089	NM_024665.7(TBL1XR1):c.41del (p.Arg14fs)	TBL1XR1	Pathogenic	criteria provided, single submitter
1453577	NM_024665.7(TBL1XR1):c.1195T>A (p.Trp399Arg)	TBL1XR1	Pathogenic	criteria provided, single submitter
1686249	NM_024665.7(TBL1XR1):c.1340G>A (p.Ser447Asn)	TBL1XR1	Pathogenic	criteria provided, single submitter
1710357	NM_024665.7(TBL1XR1):c.64dup (p.Ser22fs)	TBL1XR1	Pathogenic	criteria provided, single submitter
225873	NM_024665.7(TBL1XR1):c.734A>G (p.Tyr245Cys)	TBL1XR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225874	NM_024665.7(TBL1XR1):c.1337A>G (p.Tyr446Cys)	TBL1XR1	Pathogenic	criteria provided, multiple submitters, no conflicts
2581100	NM_024665.7(TBL1XR1):c.420dup (p.Ile141fs)	TBL1XR1	Pathogenic	criteria provided, single submitter
2628582	NM_024665.7(TBL1XR1):c.208G>T (p.Gly70Cys)	TBL1XR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2760511	NM_024665.7(TBL1XR1):c.776_780dup (p.Thr261fs)	TBL1XR1	Pathogenic	criteria provided, single submitter
2854416	NM_024665.7(TBL1XR1):c.830_831del (p.Lys277fs)	TBL1XR1	Pathogenic	criteria provided, single submitter
3640472	NM_024665.7(TBL1XR1):c.377dup (p.Asn126fs)	TBL1XR1	Pathogenic	criteria provided, single submitter
4072012	NM_024665.7(TBL1XR1):c.1195T>C (p.Trp399Arg)	TBL1XR1	Pathogenic	criteria provided, single submitter
802020	NM_024665.7(TBL1XR1):c.1184A>G (p.Tyr395Cys)	TBL1XR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802023	NM_024665.7(TBL1XR1):c.226C>T (p.Arg76Ter)	TBL1XR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
818064	NM_024665.7(TBL1XR1):c.327_357dup (p.Gln120fs)	TBL1XR1	Pathogenic	criteria provided, multiple submitters, no conflicts
857363	NM_024665.7(TBL1XR1):c.626_629del (p.Leu209fs)	TBL1XR1	Pathogenic	criteria provided, single submitter
981384	NM_024665.7(TBL1XR1):c.1291C>T (p.Arg431Ter)	TBL1XR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1708492	NM_024665.7(TBL1XR1):c.937G>A (p.Asp313Asn)	LOC126806878	Likely pathogenic	criteria provided, single submitter
647180	NM_024665.7(TBL1XR1):c.1048-1G>A	LOC126806878	Likely pathogenic	criteria provided, single submitter
802021	NM_024665.7(TBL1XR1):c.1100G>T (p.Cys367Phe)	LOC126806878	Likely pathogenic	criteria provided, single submitter
983039	NM_024665.7(TBL1XR1):c.1018_1021del (p.Arg340fs)	LOC126806878	Likely pathogenic	criteria provided, single submitter
1300134	NM_024665.7(TBL1XR1):c.679G>A (p.Asp227Asn)	TBL1XR1	Likely pathogenic	criteria provided, single submitter
1320182	NM_024665.7(TBL1XR1):c.172_173del (p.Gln58fs)	TBL1XR1	Likely pathogenic	criteria provided, single submitter
2024079	NM_024665.7(TBL1XR1):c.864+1G>A	TBL1XR1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
TBL1XR1	Definitive	Autosomal dominant	Pierpont syndrome	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBL1XR1	Orphanet:487825	Pierpont syndrome
TBL1XR1	Orphanet:520	Acute promyelocytic leukemia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TBL1XR1	HGNC:29529	ENSG00000177565	Q9BZK7	F-box-like/WD repeat-containing protein TBL1XR1	gencc,clinvar
TBL1XR1-AS1	HGNC:41243	ENSG00000231310		TBL1XR1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBL1XR1	F-box-like/WD repeat-containing protein TBL1XR1	F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TBL1XR1	Scaffold/PPI	no		WD40_rpt, LisH, WD40/YVTN_repeat-like_dom_sf
TBL1XR1-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
nipple	1
tibia	1
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBL1XR1	284	ubiquitous	marker	calcaneal tendon, nipple, tibia
TBL1XR1-AS1	117		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBL1XR1	4,066
TBL1XR1-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBL1XR1	Q9BZK7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 61. 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
Loss of MECP2 binding ability to the NCoR/SMRT complex	1	1631.4×	0.009	TBL1XR1
Loss of function of MECP2 in Rett syndrome	1	1427.5×	0.009	TBL1XR1
Pervasive developmental disorders	1	1427.5×	0.009	TBL1XR1
Disorders of Developmental Biology	1	1427.5×	0.009	TBL1XR1
Disorders of Nervous System Development	1	1427.5×	0.009	TBL1XR1
R-HSA-1368082	1	713.8×	0.010	TBL1XR1
BMAL1:CLOCK,NPAS2 activates circadian expression	1	423.0×	0.010	TBL1XR1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1	407.9×	0.010	TBL1XR1
Signaling by NOTCH1 in Cancer	1	407.9×	0.010	TBL1XR1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1	407.9×	0.010	TBL1XR1
Notch-HLH transcription pathway	1	407.9×	0.010	TBL1XR1
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	1	407.9×	0.010	TBL1XR1
NR1H2 and NR1H3-mediated signaling	1	393.8×	0.010	TBL1XR1
Regulation of MECP2 expression and activity	1	368.4×	0.010	TBL1XR1
Signaling by NOTCH1	1	356.9×	0.010	TBL1XR1
R-HSA-400253	1	346.1×	0.010	TBL1XR1
HCMV Infection	1	326.3×	0.010	TBL1XR1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.010	TBL1XR1
Transcriptional Regulation by MECP2	1	317.2×	0.010	TBL1XR1
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	308.6×	0.010	TBL1XR1
Expression of BMAL (ARNTL), CLOCK, and NPAS2	1	292.8×	0.010	TBL1XR1
Activation of gene expression by SREBF (SREBP)	1	259.6×	0.011	TBL1XR1
NOTCH1 Intracellular Domain Regulates Transcription	1	237.9×	0.011	TBL1XR1
Heme signaling	1	215.5×	0.011	TBL1XR1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	215.5×	0.011	TBL1XR1
Transcriptional activation of mitochondrial biogenesis	1	203.9×	0.011	TBL1XR1
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	196.9×	0.011	TBL1XR1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	196.9×	0.011	TBL1XR1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	196.9×	0.011	TBL1XR1
Cytoprotection by HMOX1	1	184.2×	0.011	TBL1XR1

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
regulation of triglyceride metabolic process	1	2106.5×	0.004	TBL1XR1
fat pad development	1	1685.2×	0.004	TBL1XR1
response to dietary excess	1	1123.5×	0.004	TBL1XR1
white fat cell differentiation	1	842.6×	0.004	TBL1XR1
blastocyst hatching	1	543.6×	0.005	TBL1XR1
lipid catabolic process	1	244.2×	0.010	TBL1XR1
positive regulation of canonical Wnt signaling pathway	1	154.6×	0.013	TBL1XR1
multicellular organism growth	1	137.0×	0.013	TBL1XR1
chromatin organization	1	99.1×	0.016	TBL1XR1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.027	TBL1XR1
positive regulation of DNA-templated transcription	1	27.9×	0.046	TBL1XR1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.066	TBL1XR1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.072	TBL1XR1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TBL1XR1

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
TBL1XR1	0	0
TBL1XR1-AS1	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
TBL1XR1	2	Binding:2

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	2	TBL1XR1, TBL1XR1-AS1

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)
TBL1XR1	2	—
TBL1XR1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.