PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome

Summary

PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (MONDO:0035133) is a disease caused by PHIP (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PHIP (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 182
• Phenotypes (HPO): 38

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		35	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0000400	Macrotia	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0012758	Neurodevelopmental delay	Very frequent (80-99%)
HP:0000233	Thin vermilion border	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000455	Broad nasal tip	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000539	Abnormality of refraction	Frequent (30-79%)
HP:0000540	Hypermetropia	Frequent (30-79%)
HP:0000664	Synophrys	Frequent (30-79%)
HP:0000957	Cafe-au-lait spot	Frequent (30-79%)
HP:0001182	Tapered finger	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0004324	Increased body weight	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0100710	Impulsivity	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000403	Recurrent otitis media	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000582	Upslanted palpebral fissure	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001319	Neonatal hypotonia	Occasional (5-29%)
HP:0002019	Constipation	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002378	Hand tremor	Occasional (5-29%)
HP:0002761	Generalized joint laxity	Occasional (5-29%)
HP:0002788	Recurrent upper respiratory tract infections	Occasional (5-29%)
HP:0004691	2-3 toe syndactyly	Occasional (5-29%)
HP:0007874	Almond-shaped palpebral fissure	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome
Mondo ID	MONDO:0035133
OMIM	617991
Orphanet	589905
UMLS	C4693860
MedGen	1641154
GARD	0022367
Is cancer (heuristic)	no

Also known as: Chung-Jansen syndrome · developmental delay, intellectual disability, obesity, and dysmorphic features · DIDOD

Data availability: 182 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 › PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features 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, 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, 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

182 retrieved; paginated sample, class counts are floors:

54 likely pathogenic, 44 uncertain significance, 40 pathogenic, 19 conflicting classifications of pathogenicity, 15 pathogenic/likely pathogenic, 9 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1172622	NM_017934.7(PHIP):c.3922A>T (p.Arg1308Ter)	IRAK1BP1	Pathogenic	criteria provided, single submitter
1334392	NM_017934.7(PHIP):c.4447C>T (p.Arg1483Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526063	NM_017934.7(PHIP):c.3193C>T (p.Arg1065Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1700481	NM_017934.7(PHIP):c.3801_3805del (p.Ile1268fs)	IRAK1BP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1708980	NM_017934.7(PHIP):c.4370+1G>A	IRAK1BP1	Pathogenic	criteria provided, single submitter
1709816	NM_017934.7(PHIP):c.4528C>T (p.Arg1510Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1992347	NM_017934.7(PHIP):c.4513C>T (p.Arg1505Ter)	IRAK1BP1	Pathogenic	criteria provided, multiple submitters, no conflicts
2664246	NM_017934.7(PHIP):c.3394G>T (p.Glu1132Ter)	IRAK1BP1	Pathogenic	criteria provided, single submitter
2664247	NM_017934.7(PHIP):c.3499del (p.Arg1167fs)	IRAK1BP1	Pathogenic	criteria provided, single submitter
2664250	NM_017934.7(PHIP):c.3952dup (p.Ile1318fs)	IRAK1BP1	Pathogenic	criteria provided, multiple submitters, no conflicts
3024269	NM_017934.7(PHIP):c.3243G>A (p.Trp1081Ter)	IRAK1BP1	Pathogenic	criteria provided, single submitter
3359011	NM_017934.7(PHIP):c.3297_3298del (p.Phe1100fs)	IRAK1BP1	Pathogenic	criteria provided, single submitter
39979	NM_017934.7(PHIP):c.3447T>G (p.Tyr1149Ter)	IRAK1BP1	Pathogenic	no assertion criteria provided
4279650	NM_017934.7(PHIP):c.3685C>T (p.Arg1229Ter)	IRAK1BP1	Pathogenic	criteria provided, single submitter
450225	NM_017934.7(PHIP):c.4402C>T (p.Gln1468Ter)	IRAK1BP1	Pathogenic	criteria provided, multiple submitters, no conflicts
487351	NM_017934.7(PHIP):c.3706C>T (p.Arg1236Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523846	NM_017934.7(PHIP):c.2902C>T (p.Arg968Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545398	NM_017934.7(PHIP):c.3571C>T (p.Gln1191Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	no assertion criteria provided
627522	NM_017934.7(PHIP):c.3595del (p.Thr1198_Val1199insTer)	IRAK1BP1	Pathogenic	criteria provided, single submitter
627524	NM_017934.7(PHIP):c.4570del (p.Ser1524fs)	IRAK1BP1	Pathogenic	criteria provided, single submitter
627527	NM_017934.7(PHIP):c.3161del (p.Val1053_Leu1054insTer)	IRAK1BP1	Pathogenic	criteria provided, single submitter
638583	NM_017934.7(PHIP):c.3656+1242A>T	IRAK1BP1	Pathogenic	criteria provided, single submitter
817578	NM_017934.7(PHIP):c.3947dup (p.Tyr1316Ter)	IRAK1BP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
870652	Single allele	IRAK1BP1	Pathogenic	criteria provided, single submitter
982876	NM_017934.7(PHIP):c.3110C>A (p.Ser1037Ter)	IRAK1BP1	Pathogenic	criteria provided, single submitter
984976	NM_017934.7(PHIP):c.3631_3634del (p.Gln1211fs)	IRAK1BP1	Pathogenic	criteria provided, multiple submitters, no conflicts
4530615	NM_017934.7(PHIP):c.5_9del (p.Met1_Ser2insTer)	LOC129996745	Pathogenic	criteria provided, single submitter
976441	NM_017934.7(PHIP):c.2T>C (p.Met1Thr)	LOC129996745	Pathogenic	no assertion criteria provided
1686056	NM_017934.7(PHIP):c.2703dup (p.Val902fs)	PHIP	Pathogenic	criteria provided, single submitter
1686057	NM_017934.7(PHIP):c.1186C>T (p.Arg396Ter)	PHIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · 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
PHIP	Definitive	Autosomal dominant	developmental delay, intellectual disability, obesity, and dysmorphic features	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHIP	Orphanet:589905	PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features 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
PHIP	HGNC:15673	ENSG00000146247	Q8WWQ0	PH-interacting protein	gencc,clinvar
IRAK1BP1	HGNC:17368	ENSG00000146243	Q5VVH5	Interleukin-1 receptor-associated kinase 1-binding protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHIP	PH-interacting protein	Probable regulator of the insulin and insulin-like growth factor signaling pathways.
IRAK1BP1	Interleukin-1 receptor-associated kinase 1-binding protein 1	Component of the IRAK1-dependent TNFRSF1A signaling pathway that leads to NF-kappa-B activation and is required for cell survival.

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)
PHIP	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
IRAK1BP1	Other/Unknown	no		SIMPL/DUF541, IRAK1BP1

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
bronchial epithelial cell	1
epithelium of bronchus	1
ventricular zone	1
caput epididymis	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHIP	302	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, ventricular zone
IRAK1BP1	211	ubiquitous	marker	oocyte, secondary oocyte, caput epididymis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHIP	3,057
IRAK1BP1	571

Intra-cohort edges

A	B	Sources
IRAK1BP1	PHIP	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHIP	Q8WWQ0	146

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IRAK1BP1	Q5VVH5	82.40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
RHOBTB2 GTPase cycle	1	475.8×	0.002	PHIP

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
positive regulation of insulin-like growth factor receptor signaling pathway	1	601.9×	0.013	PHIP
regulation of protein phosphorylation	1	561.7×	0.013	PHIP
regulation of cell morphogenesis	1	312.1×	0.014	PHIP
positive regulation of mitotic nuclear division	1	271.8×	0.014	PHIP
negative regulation of extrinsic apoptotic signaling pathway	1	210.7×	0.014	PHIP
insulin receptor signaling pathway	1	110.9×	0.022	PHIP
cytoskeleton organization	1	66.3×	0.030	PHIP
regulation of cell shape	1	61.5×	0.030	PHIP
positive regulation of canonical NF-kappaB signal transduction	1	36.3×	0.046	IRAK1BP1
immune response	1	23.5×	0.063	IRAK1BP1
negative regulation of apoptotic process	1	17.4×	0.073	PHIP
positive regulation of cell population proliferation	1	16.8×	0.073	PHIP
positive regulation of DNA-templated transcription	1	14.0×	0.081	PHIP
positive regulation of transcription by RNA polymerase II	1	7.4×	0.139	PHIP
regulation of transcription by RNA polymerase II	1	5.8×	0.164	PHIP

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
PHIP	0	0
IRAK1BP1	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
PHIP	17	Binding:17

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	PHIP, IRAK1BP1

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)
PHIP	17	—
IRAK1BP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.