Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
diseaseOn this page
Also known as NEDDFL
Summary
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (MONDO:0060596) is a disease caused by BPTF (GenCC Strong), with 11 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: BPTF (GenCC Strong)
- Cohort genes: 11
- ClinVar variants: 135
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 49 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | neurodevelopmental disorder with dysmorphic facies and distal limb anomalies |
| Mondo ID | MONDO:0060596 |
| OMIM | 617755 |
| Orphanet | 686482 |
| DOID | DOID:0070514 |
| UMLS | C4540327 |
| MedGen | 1627464 |
| GARD | 0018513 |
| Is cancer (heuristic) | no |
Also known as: NEDDFL · neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
Data availability: 135 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
Related subtypes (275): microcephaly and chorioretinopathy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, autosomal dominant primary microcephaly, Prader-Willi syndrome, Smith-Magenis syndrome, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, microcephalic osteodysplastic primordial dwarfism, type 3, CK syndrome, orofaciodigital syndrome I, Rett syndrome, Wieacker-Wolff syndrome, Amish lethal microcephaly, cerebral palsy, spastic quadriplegic, 2, Pitt-Hopkins-like syndrome 2, developmental delay with autism spectrum disorder and gait instability, complex cortical dysplasia with other brain malformations 5, AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome, intellectual disability, autosomal dominant 29, Au-Kline syndrome, cerebellar atrophy, visual impairment, and psychomotor retardation;, neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, cerebral palsy, spastic quadriplegic, 3, Okur-Chung neurodevelopmental syndrome, Harel-Yoon syndrome, neurodevelopmental disorder with hypotonia, seizures, and absent language, alternating hemiplegia of childhood, autosomal recessive primary microcephaly, Rubinstein-Taybi syndrome, neurodevelopmental disorder with cerebellar atrophy and with or without seizures, neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, neurodevelopmental disorder with hypotonia, microcephaly, and seizures, neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, neurodevelopmental disorder with language impairment and behavioral abnormalities, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities, neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities, neurodevelopmental disorder with or without early-onset generalized epilepsy, neurodevelopmental disorder with or without autism or seizures, neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism, neurodevelopmental disorder with dysmorphic facies and variable seizures, squalene synthase deficiency, intellectual developmental disorder and retinitis pigmentosa; IDDRP, neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, Houge-Janssens syndrome 3, neurodevelopmental disorder with central and peripheral motor dysfunction, neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, neurodevelopmental disorder with impaired speech and hyperkinetic movements, developmental delay with variable intellectual impairment and behavioral abnormalities, neurodevelopmental disorder with or without variable brain abnormalities; NEDBA, neurodevelopmental disorder with seizures and speech and walking impairment, neurodevelopmental disorder with microcephaly and structural brain anomalies, neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, neurodevelopmental disorder with visual defects and brain anomalies, neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, neurodevelopmental disorder with cerebellar hypoplasia and spasticity, neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies, neurodevelopmental disorder with absent language and variable seizures, neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures, neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, Poirier-Bienvenu neurodevelopmental syndrome, neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements, neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation, neurodevelopmental disorder with microcephaly and dysmorphic facies, neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies, neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia, neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, neurodevelopmental disorder with speech impairment and dysmorphic facies, neurodevelopmental disorder with alopecia and brain abnormalities, neurodevelopmental disorder with seizures and brain atrophy, neurodevelopmental disorder with microcephaly, seizures, and brain atrophy, Delpire-McNeill syndrome, neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination, developmental delay and seizures with or without movement abnormalities, Stankiewicz-Isidor syndrome, neurodevelopmental disorder with midbrain and hindbrain malformations, neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies, neurodevelopmental disorder with involuntary movements, neurodevelopmental disorder with hypotonia, neuropathy, and deafness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, neurodevelopmental disorder with microcephaly, ataxia, and seizures, neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy, neurodevelopmental disorder with severe motor impairment and absent language, neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, neurodevelopmental disorder with or without seizures and gait abnormalities, neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, neurodevelopmental disorder with poor language and loss of hand skills, neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, neurodevelopmental disorder with spasticity and poor growth, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, FOXG1 disorder, genetic developmental and epileptic encephalopathy, X-linked complex neurodevelopmental disorder, PPP2R1A-related intellectual disability, intellectual disability, autosomal dominant, CACNA1A-related complex neurodevelopmental disorder, X-linked intellectual disability, PAX5-related B lymphopenia and autism spectrum disorder, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, KCNH1 associated disorder, AFG2B-related complex neurodevelopmental disorder with motor features and hearing loss, intellectual disability, autosomal recessive, FAT4-related neurodevelopmental disorder, SOX11-related complex neurodevelopmental disorder with or without congenital anomalies, microcephaly with lissencephaly and/or hydranencephaly, MYH10-related neurodevelopmental disorder with congenital anomalies, CNOT9-related developmental disorder with seizures, HMGB1-related brachyphalangy, polydactyly and tibial aplasia syndrome, ATXN7L3-related developmental delay, hypotonia and facial dysmorphism, DIP2C-related developmental disorder with speech delay, EPB41L3-related developmental disorder with delayed myelination and seizures, GABRA4-related neurodevelopmental disorder with seizures, GABRD-related neurodevelopmental disorder with epilepsy, KCNK3-related developmental delay with sleep apnea, RFX3-related neurodevelopmental disorder with autism and other behavioural abnormalities, RFX4-related neurodevelopmental disorder with autism and other behavioural abnormalities, KDM2B-related neurodevelopmental disorder, TRA2B-related neurodevelopmental disorder, WDR5-related neurodevelopmental disorder, ARF3-related neurodevelopmental disorder, CBX1-related neurodevelopmental disorder, DDX17-related neurodevelopmental disorder, FEZF2-related neurodevelopmental disorder, HDAC3-related neurodevelopmental disorder, DEAF1-associated neurodevelopmental disorder, SYNCRIP-related neurodevelopmental disorder, HNRNPC-related neurodevelopmental disorder, NACC1-related neurodevelopmental disorder with epilepsy, cataracts and episodic irritability, SETD2-related neurodevelopmental disorder without or with macrocephaly/overgrowth, neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked, Alzahrani-Kuwahara syndrome, neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, Hiatt-Neu-Cooper neurodevelopmental syndrome, neurodevelopmental disorder with seizures and gingival overgrowth, neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, neurodevelopmental disorder with infantile epileptic spasms, neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, neurodevelopmental disorder with motor and speech delay and behavioral abnormalities, neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, neurodevelopmental disorder with hypotonia and dysmorphic facies, neurodevelopmental disorder with hypotonia and brain abnormalities, neurodevelopmental disorder with impaired language and ataxia and with or without seizures, neurodevelopmental disorder with hearing loss and spasticity, neurodevelopmental disorder with hypotonia and gross motor and speech delay, neurodevelopmental disorder with hyperkinetic movements and dyskinesia, neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, Marbach-Schaaf neurodevelopmental syndrome, neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis, Brunet-Wagner neurodevelopmental syndrome, Ferguson-Bonni neurodevelopmental syndrome, neurodevelopmental disorder with or without variable movement or behavioral abnormalities, neurodevelopmental disorder with central hypotonia and dysmorphic facies, neurodevelopmental disorder with neuromuscular and skeletal abnormalities, Chilton-Okur-Chung neurodevelopmental syndrome, neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities, parenti-mignot neurodevelopmental syndrome, neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures, Dentici-Novelli neurodevelopmental syndrome, neurodevelopmental disorder with poor growth and skeletal anomalies, neurodevelopmental disorder with language delay and seizures, neurodevelopmental disorder with dystonia and seizures, Dworschak-Punetha neurodevelopmental syndrome, neurodevelopmental disorder with epilepsy and brain atrophy, neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, neurodevelopmental disorder with speech delay and variable ocular anomalies, neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, neurodevelopmental disorder with spasticity, seizures, and brain abnormalities, neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, neurodevelopmental disorder with microcephaly, short stature, and speech delay, neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures, neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly, neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, neurodevelopmental disorder with eye movement abnormalities and ataxia, neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, neurodevelopmental disorder with speech impairment and with or without seizures, neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia, neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, neurodevelopmental disorder with poor growth and behavioral abnormalities, neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, neurodevelopmental disorder with absent speech and movement and behavioral abnormalities, neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, neurodevelopmental disorder with microcephaly and movement abnormalities, neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, neurodevelopmental disorder with language delay and variable cognitive abnormalities, neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, Hao-Fountain syndrome due to USP7 mutation, neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, neurodevelopmental disorder with hyperkinetic movements, seizures, and structural brain abnormalities, neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, Jeffries-Lakhani neurodevelopmental syndrome, neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder, neurodevelopmental disorder plus optic atrophy, neurodevelopmental disorder with progressive movement abnormalities, aplasia cutis-enamel dysplasia syndrome, neurodevelopmental disorder with hypotonia and seizures, El Hayek-Chahrour neurodevelopmental disorder, neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, otofacial neurodevelopmental syndrome, neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, Kariminejad neurodevelopmental syndrome, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, intellectual developmental disorder with polymicrogyria and seizures, neurodevelopmental disorder with speech or visual impairment and brain hypomyelination, neurodevelopmental disorder with microcephaly, absent speech, and hypotonia, neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia, neurodevelopmental disorder with progressive spasticity and brain abnormalities, neurodevelopmental disorder with thin corpus callosum, hypotonia, and absent language, neurodevelopmental disorder with white matter abnormalities and gait disturbance, neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalities, neurodevelopmental disorder with ataxia and brain abnormalities, neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, Li-Takada-Miyake syndrome, neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities, Nil-Deshwar neurodevelopmental syndrome, Popov-Chang syndrome, neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima, Dursun-Ozgul neurodevelopmental syndrome, neurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speech, neurodevelopmental disorder with speech delay and behavioral abnormalities, Harel-Tora neurodevelopmental syndrome, neurocardiorenal malformation syndrome, neurodevelopmental disorder with behavioral abnormalities and childhood-onset spastic paraplegia, neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, neurodevelopmental disorder with structural brain abnormalities and craniofacial abnormalities, Ramond-Elliott neurodevelopmental syndrome, microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter, neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities, neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, PIP5K1C-related neurodevelopmental disorder, KCND2-related neurodevelopmental disorder with or without seizures, PRPF19-related neurodevelopmental disorder, CTR9-related neurodevelopmental disorder, CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy, PPFIA3-related neurodevelopmental disorder, dyneinopathy, MYCBP2-related developmental delay with corpus callosum defects, GRIN-related complex neurodevelopmental disorder, RNU5B-1 related neurodevelopmental disorder with seizures and joint laxity, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy
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
135 retrieved; paginated sample, class counts are floors:
70 uncertain significance, 23 likely pathogenic, 21 pathogenic, 9 conflicting classifications of pathogenicity, 5 benign/likely benign, 4 pathogenic/likely pathogenic, 2 benign, 1 not provided
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1174080 | NM_182641.4(BPTF):c.5575_5576del (p.Arg1859fs) | BPTF | Pathogenic | no assertion criteria provided |
| 1319921 | NM_182641.4(BPTF):c.1999C>T (p.Gln667Ter) | BPTF | Pathogenic | no assertion criteria provided |
| 1319947 | NM_182641.4(BPTF):c.7960_7961del (p.Glu2654fs) | BPTF | Pathogenic | no assertion criteria provided |
| 1330710 | NM_182641.4(BPTF):c.6562_6563del (p.Val2188fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 1693493 | NM_182641.4(BPTF):c.209dup (p.Ser71fs) | BPTF | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3068507 | NM_182641.4(BPTF):c.7776dup (p.Arg2593fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 3254960 | NM_182641.4(BPTF):c.3157_3158del (p.Lys1053fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 3377266 | NM_182641.4(BPTF):c.5854dup (p.Ala1952fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 3679943 | NM_182641.4(BPTF):c.8572C>T (p.Arg2858Ter) | BPTF | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 4292692 | NM_182641.4(BPTF):c.3964C>T (p.Arg1322Ter) | BPTF | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 431064 | NM_182641.4(BPTF):c.2482dup (p.Glu828fs) | BPTF | Pathogenic | no assertion criteria provided |
| 431065 | NM_182641.4(BPTF):c.4838_4839del (p.Val1613fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 431066 | NM_182641.4(BPTF):c.8701A>T (p.Lys2901Ter) | BPTF | Pathogenic | no assertion criteria provided |
| 431071 | NM_182641.4(BPTF):c.8609T>G (p.Met2870Arg) | BPTF | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 431072 | NM_182641.4(BPTF):c.989del (p.Leu330fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 4526450 | NM_182641.4(BPTF):c.2597_2600del (p.Lys866fs) | BPTF | Pathogenic | no assertion criteria provided |
| 4819904 | NM_182641.4(BPTF):c.2385_2388del (p.Leu796fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 4847311 | NM_182641.4(BPTF):c.1691dup (p.Asp566fs) | BPTF | Pathogenic | criteria provided, single submitter |
| 828184 | NM_182641.4(BPTF):c.255del (p.Ser86fs) | BPTF | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 976787 | NM_182641.4(BPTF):c.52_61del (p.Glu18fs) | BPTF | Pathogenic | no assertion criteria provided |
| 617475 | NM_003754.3(EIF3F):c.694T>G (p.Phe232Val) | EIF3F | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2664088 | NC_000010.11:g.79055368_79303220del | LOC124416852 | Pathogenic | criteria provided, single submitter |
| 236407 | NM_000310.4(PPT1):c.713C>T (p.Pro238Leu) | PPT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2430127 | NM_014712.3(SETD1A):c.2825del (p.Pro942fs) | SETD1A | Pathogenic | criteria provided, single submitter |
| 1801330 | NM_001162501.2(TNRC6B):c.1660del (p.Gln554fs) | TNRC6B | Pathogenic | criteria provided, single submitter |
| 1028759 | NM_182641.4(BPTF):c.2798A>T (p.Lys933Met) | BPTF | Likely pathogenic | criteria provided, single submitter |
| 1031427 | NM_182641.4(BPTF):c.8552T>G (p.Met2851Arg) | BPTF | Likely pathogenic | criteria provided, single submitter |
| 1334084 | NM_182641.4(BPTF):c.1132C>T (p.Arg378Ter) | BPTF | Likely pathogenic | criteria provided, single submitter |
| 1341680 | NM_182641.4(BPTF):c.5564del (p.Pro1855fs) | BPTF | Likely pathogenic | no assertion criteria provided |
| 1341681 | NM_182641.4(BPTF):c.1133G>A (p.Arg378Gln) | BPTF | Likely pathogenic | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 30 · 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 |
|---|---|---|---|---|
| BPTF | Strong | Autosomal dominant | neurodevelopmental disorder with dysmorphic facies and distal limb anomalies | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| BPTF | Orphanet:529962 | 17q24.2 microdeletion syndrome |
| BPTF | Orphanet:686482 | BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome |
| SHH | Orphanet:220386 | Semilobar holoprosencephaly |
| SHH | Orphanet:280195 | Septopreoptic holoprosencephaly |
| SHH | Orphanet:280200 | Microform holoprosencephaly |
| SHH | Orphanet:476119 | Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome |
| SHH | Orphanet:485275 | Acquired schizencephaly |
| SHH | Orphanet:93321 | Isolated radial hemimelia |
| SHH | Orphanet:93336 | Polydactyly of a triphalangeal thumb |
| SHH | Orphanet:93405 | Syndactyly type 4 |
| SHH | Orphanet:93924 | Lobar holoprosencephaly |
| SHH | Orphanet:93925 | Alobar holoprosencephaly |
| SHH | Orphanet:93926 | Midline interhemispheric variant of holoprosencephaly |
| SHH | Orphanet:988 | Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome |
| SHH | Orphanet:98938 | Colobomatous microphthalmia |
| CACNA1C | Orphanet:101016 | Romano-Ward syndrome |
| CACNA1C | Orphanet:130 | Brugada syndrome |
| CACNA1C | Orphanet:528084 | Non-specific syndromic intellectual disability |
| CACNA1C | Orphanet:595098 | Timothy syndrome type 1 |
| CACNA1C | Orphanet:595105 | Timothy syndrome type 2 |
| CACNA1C | Orphanet:595109 | Atypical Timothy syndrome |
| KMT2E | Orphanet:528084 | Non-specific syndromic intellectual disability |
| SCAF4 | Orphanet:528084 | Non-specific syndromic intellectual disability |
| SETD1A | Orphanet:528084 | Non-specific syndromic intellectual disability |
| TNRC6B | Orphanet:528084 | Non-specific syndromic intellectual disability |
| PPT1 | Orphanet:699718 | Infantile CLN1 disease |
| PPT1 | Orphanet:699734 | Late infantile CLN1 disease |
| PPT1 | Orphanet:699739 | Juvenile CLN1 disease |
| PPT1 | Orphanet:699745 | Adult CLN1 disease |
| RAC1 | Orphanet:500159 | Microcephaly-corpus callosum and cerebellar vermis hypoplasia-facial dysmorphism-intellectual disability syndrom |
Cohort genes → proteins
11 cohort genes, 11 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 11 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| BPTF | HGNC:3581 | ENSG00000171634 | Q12830 | Nucleosome-remodeling factor subunit BPTF | gencc,clinvar |
| RNASE1 | HGNC:10044 | ENSG00000129538 | P07998 | Ribonuclease pancreatic | clinvar |
| SHH | HGNC:10848 | ENSG00000164690 | Q15465 | Sonic hedgehog protein | clinvar |
| CACNA1C | HGNC:1390 | ENSG00000151067 | Q13936 | Voltage-dependent L-type calcium channel subunit alpha-1C | clinvar |
| KMT2E | HGNC:18541 | ENSG00000005483 | Q8IZD2 | Inactive histone-lysine N-methyltransferase 2E | clinvar |
| SCAF4 | HGNC:19304 | ENSG00000156304 | O95104 | SR-related and CTD-associated factor 4 | clinvar |
| SETD1A | HGNC:29010 | ENSG00000099381 | O15047 | Histone-lysine N-methyltransferase SETD1A | clinvar |
| TNRC6B | HGNC:29190 | ENSG00000100354 | Q9UPQ9 | Trinucleotide repeat-containing gene 6B protein | clinvar |
| EIF3F | HGNC:3275 | ENSG00000175390 | O00303 | Eukaryotic translation initiation factor 3 subunit F | clinvar |
| PPT1 | HGNC:9325 | ENSG00000131238 | P50897 | Palmitoyl-protein thioesterase 1 | clinvar |
| RAC1 | HGNC:9801 | ENSG00000136238 | P63000 | Ras-related C3 botulinum toxin substrate 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| BPTF | Nucleosome-remodeling factor subunit BPTF | Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcrip… |
| RNASE1 | Ribonuclease pancreatic | Endonuclease that catalyzes the cleavage of RNA on the 3’ side of pyrimidine nucleotides. |
| SHH | Sonic hedgehog protein | The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity. |
| CACNA1C | Voltage-dependent L-type calcium channel subunit alpha-1C | Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. |
| KMT2E | Inactive histone-lysine N-methyltransferase 2E | Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription. |
| SCAF4 | SR-related and CTD-associated factor 4 | Anti-terminator protein required to prevent early mRNA termination during transcription. |
| SETD1A | Histone-lysine N-methyltransferase SETD1A | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism. |
| TNRC6B | Trinucleotide repeat-containing gene 6B protein | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). |
| EIF3F | Eukaryotic translation initiation factor 3 subunit F | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. |
| PPT1 | Palmitoyl-protein thioesterase 1 | Has thioesterase activity against fatty acid thioesters with 14 -18 carbons, including palmitoyl-CoA, S-palmitoyl-N-acetylcysteamine, and palmitoylated proteins. |
| RAC1 | Ras-related C3 botulinum toxin substrate 1 | Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. |
Protein-family classification
Druggable: 5 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.45
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 |
|---|---|---|---|
| Enzyme (other) | 4 | 4.4× | 0.039 |
| Ion channel | 1 | 10.1× | 0.189 |
| Transcription factor | 2 | 1.5× | 0.523 |
| Other/Unknown | 4 | 0.7× | 0.946 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| BPTF | Transcription factor | no | Bromodomain, Znf_PHD, Znf_FYVE_PHD | |
| RNASE1 | Enzyme (other) | yes | 4.6.1.18 | RNaseA, RNaseA_AS, RNaseA_domain |
| SHH | Other/Unknown | no | Hedgehog_signalling_dom, Hedgehog, Hedgehog_Hint | |
| CACNA1C | Ion channel | yes | VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu | |
| KMT2E | Transcription factor | no | SET_dom, Znf_PHD, Znf_FYVE_PHD | |
| SCAF4 | Other/Unknown | no | RRM_dom, CID_dom, ENTH_VHS | |
| SETD1A | Enzyme (other) | yes | 2.1.1.354 | RRM_dom, SET_dom, Post-SET_dom |
| TNRC6B | Other/Unknown | no | Nucleotide-bd_a/b_plait_sf, Argonaute_hook_dom, TNRC6_PABC-bd | |
| EIF3F | Other/Unknown | no | JAMM/MPN+_dom, EIF3F/CSN6-like_C, eIF3f | |
| PPT1 | Enzyme (other) | yes | 3.1.2.2 | Palm_thioest, AB_hydrolase_fold |
| RAC1 | Enzyme (other) | yes | 3.6.5.2 | Small_GTPase, Small_GTPase_Rho, Small_GTP-bd |
Expression context
Cohort genes with no expression data: 0.
11 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) | 11 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| buccal mucosa cell | 3 |
| sural nerve | 2 |
| tendon of biceps brachii | 2 |
| cortical plate | 1 |
| ventricular zone | 1 |
| left testis | 1 |
| right lung | 1 |
| right testis | 1 |
| epithelial cell of pancreas | 1 |
| right lobe of liver | 1 |
| apex of heart | 1 |
| muscle layer of sigmoid colon | 1 |
| right coronary artery | 1 |
| mucosa of paranasal sinus | 1 |
| tendon | 1 |
| sperm | 1 |
| paraflocculus | 1 |
| parotid gland | 1 |
| epithelium of nasopharynx | 1 |
| nasopharynx | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| BPTF | 290 | ubiquitous | marker | sural nerve, ventricular zone, cortical plate |
| RNASE1 | 283 | broad | marker | left testis, right testis, right lung |
| SHH | 131 | broad | marker | buccal mucosa cell, right lobe of liver, epithelial cell of pancreas |
| CACNA1C | 134 | broad | marker | apex of heart, right coronary artery, muscle layer of sigmoid colon |
| KMT2E | 264 | ubiquitous | marker | tendon of biceps brachii, tendon, mucosa of paranasal sinus |
| SCAF4 | 267 | ubiquitous | marker | tendon of biceps brachii, buccal mucosa cell, sperm |
| SETD1A | 234 | ubiquitous | marker | paraflocculus, sural nerve, parotid gland |
| TNRC6B | 289 | ubiquitous | marker | buccal mucosa cell, epithelium of nasopharynx, nasopharynx |
| EIF3F | 261 | ubiquitous | marker | primordial germ cell in gonad, ganglionic eminence, left ovary |
| PPT1 | 294 | ubiquitous | marker | monocyte, mononuclear cell, leukocyte |
| RAC1 | 295 | ubiquitous | marker | esophagus squamous epithelium, epithelium of esophagus, visceral pleura |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SHH | 4,953 |
| EIF3F | 4,287 |
| SETD1A | 3,862 |
| CACNA1C | 3,145 |
| BPTF | 2,682 |
| PPT1 | 2,444 |
| KMT2E | 2,340 |
| RAC1 | 2,182 |
| SCAF4 | 2,068 |
| TNRC6B | 2,064 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| KMT2E | SETD1A | string_interaction |
Structural data
PDB: 10 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| RAC1 | P63000 | 79 |
| BPTF | Q12830 | 45 |
| CACNA1C | Q13936 | 33 |
| EIF3F | O00303 | 27 |
| SHH | Q15465 | 20 |
| RNASE1 | P07998 | 12 |
| SETD1A | O15047 | 4 |
| KMT2E | Q8IZD2 | 3 |
| SCAF4 | O95104 | 1 |
| PPT1 | P50897 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| TNRC6B | Q9UPQ9 | 39.58 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 123. Enrichment computed across 11 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Developmental Lineage of Pancreatic Acinar Cells | 2 | 75.1× | 0.033 | RNASE1, SHH |
| Developmental Cell Lineages | 2 | 56.0× | 0.033 | RNASE1, SHH |
| HHAT G278V doesn’t palmitoylate Hh-Np | 1 | 285.5× | 0.039 | SHH |
| Formation of lateral plate mesoderm | 1 | 285.5× | 0.039 | SHH |
| NTRK2 activates RAC1 | 1 | 237.9× | 0.039 | RAC1 |
| Activated NTRK2 signals through CDK5 | 1 | 237.9× | 0.039 | RAC1 |
| Post-transcriptional silencing by small RNAs | 1 | 203.9× | 0.039 | TNRC6B |
| Sema4D mediated inhibition of cell attachment and migration | 1 | 178.4× | 0.039 | RAC1 |
| Inactivation of CDC42 and RAC1 | 1 | 178.4× | 0.039 | RAC1 |
| Release of Hh-Np from the secreting cell | 1 | 178.4× | 0.039 | SHH |
| Hh mutants abrogate ligand secretion | 1 | 178.4× | 0.039 | SHH |
| Ligand-receptor interactions | 1 | 178.4× | 0.039 | SHH |
| Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 1 | 178.4× | 0.039 | TNRC6B |
| Activation of RAC1 downstream of NMDARs | 1 | 178.4× | 0.039 | RAC1 |
| Nef and signal transduction | 1 | 158.6× | 0.039 | RAC1 |
| Regulation of CDH11 mRNA translation by microRNAs | 1 | 158.6× | 0.039 | TNRC6B |
| Regulation of NPAS4 mRNA translation | 1 | 158.6× | 0.039 | TNRC6B |
| Regulation of PD-L1(CD274) translation | 1 | 158.6× | 0.039 | TNRC6B |
| MAPK6/MAPK4 signaling | 2 | 34.0× | 0.039 | TNRC6B, RAC1 |
| RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function | 2 | 30.1× | 0.039 | SETD1A, TNRC6B |
| Regulation of PTEN mRNA translation | 1 | 142.8× | 0.039 | TNRC6B |
| RHO GTPases activate KTN1 | 1 | 129.8× | 0.039 | RAC1 |
| MET activates RAP1 and RAC1 | 1 | 129.8× | 0.039 | RAC1 |
| Regulation of CDH1 mRNA translation by microRNAs | 1 | 129.8× | 0.039 | TNRC6B |
| WNT5:FZD7-mediated leishmania damping | 1 | 119.0× | 0.041 | RAC1 |
| CD28 dependent Vav1 pathway | 1 | 109.8× | 0.041 | RAC1 |
| Activation of RAC1 | 1 | 102.0× | 0.041 | RAC1 |
| PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases | 1 | 102.0× | 0.041 | RAC1 |
| Formation of axial mesoderm | 1 | 102.0× | 0.041 | SHH |
| SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 1 | 95.2× | 0.042 | RAC1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| polarity specification of anterior/posterior axis | 1 | 1532.0× | 0.011 | SHH |
| anatomical structure arrangement | 1 | 1532.0× | 0.011 | RAC1 |
| trachea morphogenesis | 1 | 1532.0× | 0.011 | SHH |
| right lung development | 1 | 1532.0× | 0.011 | SHH |
| left lung development | 1 | 1532.0× | 0.011 | SHH |
| primary prostatic bud elongation | 1 | 1532.0× | 0.011 | SHH |
| regulation of prostatic bud formation | 1 | 1532.0× | 0.011 | SHH |
| obsolete regulation of mesenchymal cell proliferation involved in prostate gland development | 1 | 1532.0× | 0.011 | SHH |
| mesenchymal smoothened signaling pathway involved in prostate gland development | 1 | 1532.0× | 0.011 | SHH |
| positive regulation of sclerotome development | 1 | 1532.0× | 0.011 | SHH |
| tracheoesophageal septum formation | 1 | 1532.0× | 0.011 | SHH |
| negative regulation of ureter smooth muscle cell differentiation | 1 | 1532.0× | 0.011 | SHH |
| positive regulation of ureter smooth muscle cell differentiation | 1 | 1532.0× | 0.011 | SHH |
| negative regulation of kidney smooth muscle cell differentiation | 1 | 1532.0× | 0.011 | SHH |
| positive regulation of kidney smooth muscle cell differentiation | 1 | 1532.0× | 0.011 | SHH |
| embryonic forelimb morphogenesis | 2 | 90.1× | 0.011 | SHH, CACNA1C |
| camera-type eye development | 2 | 65.2× | 0.011 | SHH, CACNA1C |
| brain development | 3 | 21.7× | 0.011 | BPTF, SETD1A, PPT1 |
| positive regulation of skeletal muscle cell proliferation | 1 | 766.0× | 0.013 | SHH |
| intein-mediated protein splicing | 1 | 766.0× | 0.013 | SHH |
| embryonic olfactory bulb interneuron precursor migration | 1 | 766.0× | 0.013 | RAC1 |
| cerebral cortex GABAergic interneuron development | 1 | 766.0× | 0.013 | RAC1 |
| negative regulation of interleukin-23 production | 1 | 766.0× | 0.013 | RAC1 |
| trunk neural crest cell migration | 1 | 766.0× | 0.013 | SHH |
| regulation of ERK5 cascade | 1 | 766.0× | 0.013 | RAC1 |
| angiotensin-activated signaling pathway involved in heart process | 1 | 766.0× | 0.013 | RAC1 |
| regulation of nodal signaling pathway | 1 | 766.0× | 0.013 | SHH |
| positive regulation of ovarian follicle development | 1 | 766.0× | 0.013 | RAC1 |
| positive regulation of mesenchymal cell proliferation involved in ureter development | 1 | 766.0× | 0.013 | SHH |
| negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled | 1 | 766.0× | 0.013 | SCAF4 |
Therapeutics
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 5 · Undrugged: 6
Druggability breadth: 9 of 11 evidence-associated genes (82%) 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 |
|---|---|
| SHH | VISMODEGIB |
| CACNA1C | REMIFENTANIL |
| RAC1 | KETOROLAC |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| CACNA1C | 85 | 4 |
| RAC1 | 3 | 4 |
| BPTF | 2 | 2 |
| SHH | 1 | 4 |
| SETD1A | 1 | 2 |
| RNASE1 | 0 | 0 |
| KMT2E | 0 | 0 |
| SCAF4 | 0 | 0 |
| TNRC6B | 0 | 0 |
| EIF3F | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| VISMODEGIB | 4 | SHH |
| REMIFENTANIL | 4 | CACNA1C |
| BEPRIDIL | 4 | CACNA1C |
| CLOTRIMAZOLE | 4 | CACNA1C |
| PROPIVERINE | 4 | CACNA1C |
| DIBUCAINE | 4 | CACNA1C |
| IMIPRAMINE | 4 | CACNA1C |
| DULOXETINE | 4 | CACNA1C |
| QUINIDINE | 4 | CACNA1C |
| ESTRADIOL | 4 | CACNA1C |
| TOLTERODINE | 4 | CACNA1C |
| PIMOZIDE | 4 | CACNA1C |
| NIMODIPINE | 4 | CACNA1C |
| NICARDIPINE | 4 | CACNA1C |
| AMLODIPINE | 4 | CACNA1C |
| VARDENAFIL | 4 | CACNA1C |
| CLEMASTINE | 4 | CACNA1C |
| ISRADIPINE | 4 | CACNA1C |
| TERFENADINE | 4 | CACNA1C |
| NISOLDIPINE | 4 | CACNA1C |
| SOLIFENACIN | 4 | CACNA1C |
| PINAVERIUM | 4 | CACNA1C |
| SILDENAFIL | 4 | CACNA1C |
| NIFEDIPINE | 4 | CACNA1C |
| XANOMELINE | 4 | CACNA1C |
| DILTIAZEM | 4 | CACNA1C |
| PRENYLAMINE | 4 | CACNA1C |
| OLICERIDINE | 4 | CACNA1C |
| PROPRANOLOL | 4 | CACNA1C |
| ALVIMOPAN | 4 | CACNA1C |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 4.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| CACNA1C | 575 | Binding:319, Functional:211, Toxicity:26, ADMET:19 |
| BPTF | 125 | Binding:123, Functional:2 |
| RAC1 | 74 | Binding:74 |
| SHH | 27 | Binding:23, Functional:4 |
| RNASE1 | 17 | Binding:16, ADMET:1 |
| SETD1A | 8 | Binding:8 |
| PPT1 | 5 | Binding:5 |
| EIF3F | 4 | Binding:4 |
| KMT2E | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| RNASE1 | 4.6.1.18 | pancreatic ribonuclease |
| SETD1A | 2.1.1.354 | [histone H3]-lysine4 N-trimethyltransferase |
| PPT1 | 3.1.2.2, 3.1.2.22 | palmitoyl-CoA hydrolase, palmitoyl[protein] hydrolase |
| RAC1 | 3.6.5.2 | small monomeric GTPase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| BPTF | 125 |
| CACNA1C | 575 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 11; 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) |
|---|---|---|
| VISMODEGIB | 4 | SHH |
| REMIFENTANIL | 4 | CACNA1C |
| BEPRIDIL | 4 | CACNA1C |
| CLOTRIMAZOLE | 4 | CACNA1C |
| PROPIVERINE | 4 | CACNA1C |
| DIBUCAINE | 4 | CACNA1C |
| IMIPRAMINE | 4 | CACNA1C |
| DULOXETINE | 4 | CACNA1C |
| QUINIDINE | 4 | CACNA1C |
| ESTRADIOL | 4 | CACNA1C |
| TOLTERODINE | 4 | CACNA1C |
| PIMOZIDE | 4 | CACNA1C |
| NIMODIPINE | 4 | CACNA1C |
| NICARDIPINE | 4 | CACNA1C |
| AMLODIPINE | 4 | CACNA1C |
| VARDENAFIL | 4 | CACNA1C |
| CLEMASTINE | 4 | CACNA1C |
| ISRADIPINE | 4 | CACNA1C |
| TERFENADINE | 4 | CACNA1C |
| NISOLDIPINE | 4 | CACNA1C |
| SOLIFENACIN | 4 | CACNA1C |
| PINAVERIUM | 4 | CACNA1C |
| SILDENAFIL | 4 | CACNA1C |
| NIFEDIPINE | 4 | CACNA1C |
| XANOMELINE | 4 | CACNA1C |
| DILTIAZEM | 4 | CACNA1C |
| PRENYLAMINE | 4 | CACNA1C |
| OLICERIDINE | 4 | CACNA1C |
| PROPRANOLOL | 4 | CACNA1C |
| ALVIMOPAN | 4 | CACNA1C |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | SHH, CACNA1C, RAC1 |
| B | Phased (≥1) drug, not yet approved | 2 | BPTF, SETD1A |
| C | Druggable family + PDB, no drug | 2 | RNASE1, PPT1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 4 | KMT2E, SCAF4, TNRC6B, EIF3F |
Undrugged target profiles
6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| KMT2E | 1 | SETD1A |
| RNASE1 | 17 | — |
| SCAF4 | 0 | — |
| TNRC6B | 0 | — |
| EIF3F | 4 | — |
| PPT1 | 5 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.