Dubowitz syndrome

Summary

Dubowitz syndrome (MONDO:0009124) is a disease with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 102

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.2	Europe	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000506	Telecanthus	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0009601	Aplasia/Hypoplasia of the thumb	Very frequent (80-99%)
HP:0009602	Abnormality of thumb phalanx	Very frequent (80-99%)
HP:0009891	Underdeveloped supraorbital ridges	Very frequent (80-99%)
HP:0011304	Broad thumb	Very frequent (80-99%)
HP:0000176	Submucous cleft hard palate	Frequent (30-79%)
HP:0000260	Wide anterior fontanel	Frequent (30-79%)
HP:0000270	Delayed cranial suture closure	Frequent (30-79%)
HP:0000275	Narrow face	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000294	Low anterior hairline	Frequent (30-79%)
HP:0000340	Sloping forehead	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000403	Recurrent otitis media	Frequent (30-79%)
HP:0000411	Protruding ear	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000581	Blepharophimosis	Frequent (30-79%)
HP:0000964	Eczematoid dermatitis	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001609	Hoarse voice	Frequent (30-79%)
HP:0001620	Abnormally high-pitched voice	Frequent (30-79%)
HP:0001773	Short foot	Frequent (30-79%)
HP:0001852	Sandal gap	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0002209	Sparse scalp hair	Frequent (30-79%)
HP:0002213	Fine hair	Frequent (30-79%)
HP:0002719	Recurrent infections	Frequent (30-79%)
HP:0002750	Delayed skeletal maturation	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0005338	Sparse lateral eyebrow	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0009738	Abnormality of the antihelix	Frequent (30-79%)
HP:0012758	Neurodevelopmental delay	Frequent (30-79%)
HP:0200055	Small hand	Frequent (30-79%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000047	Hypospadias	Frequent (30-79%)
HP:0000055	Abnormality of female external genitalia	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000164	Abnormality of the dentition	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Dubowitz syndrome
Mondo ID	MONDO:0009124
MeSH	C535718
OMIM	223370
Orphanet	235
DOID	DOID:14796
ICD-11	758537040
NCIT	C125591
SNOMED CT	2593002
UMLS	C0175691
MedGen	59797
GARD	0006290
MedDRA	10059589
NORD	1064
Is cancer (heuristic)	no

Also known as: Dubowitz syndrome · dwarfism-eczema-peculiar facies syndrome · intrauterine growth retardation, short stature, microcephaly, mild intellectual disability with behavior problems, eczema, and unusual and distinctive faci · intrauterine growth retardation, short stature, microcephaly, mild intellectual disability with behaviour problems, eczema, and unusual and distinctive faci · intrauterine growth retardation, short stature, microcephaly, mild mental retardation with behavior problems, eczema, and unusual and distinctive faci · intrauterine growth retardation, short stature, microcephaly, mild mental retardation with behaviour problems, eczema, and unusual and distinctive faci

Data availability: 2 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome-intellectual disability › Dubowitz syndrome

Related subtypes (337): Neu-Laxova syndrome, acrofacial dysostosis, Catania type, aortic arch anomaly-facial dysmorphism-intellectual disability syndrome, blepharonasofacial malformation syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, craniofaciofrontodigital syndrome, uveal coloboma-cleft lip and palate-intellectual disability, Ramos-Arroyo syndrome, extrasystoles-short stature-hyperpigmentation-microcephaly syndrome, Floating-Harbor syndrome, Myhre syndrome, hirsutism-skeletal dysplasia-intellectual disability syndrome, Johnson neuroectodermal syndrome, KBG syndrome, trichorhinophalangeal syndrome type II, Lenz-Majewski hyperostotic dwarfism, Bannayan-Riley-Ruvalcaba syndrome, microcephaly-deafness-intellectual disability syndrome, ophthalmoplegia-intellectual disability-lingua scrotalis syndrome, omphalocele syndrome, Shprintzen-Goldberg type, Shprintzen-Goldberg syndrome, Smith-Magenis syndrome, delayed speech-facial asymmetry-strabismus-ear lobe creases syndrome, holoprosencephaly-radial heart renal anomalies syndrome, Wolf-Hirschhorn syndrome, pseudoprogeria syndrome, acrocallosal syndrome, acrofacial dysostosis Rodriguez type, agnathia-otocephaly complex, Stimmler syndrome, anencephaly 1, aniridia-renal agenesis-psychomotor retardation syndrome, Biemond syndrome type 2, bird headed-dwarfism, Montreal type, Bowen-Conradi syndrome, Elsahy-Waters syndrome, C syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, Cohen syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Costello syndrome, temtamy syndrome, cardiocranial syndrome, Pfeiffer type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, Bonnemann-Meinecke-Reich syndrome, epilepsy-telangiectasia syndrome, faciocardiorenal syndrome, fountain syndrome, Fryns syndrome, GAPO syndrome, Hall-Riggs syndrome, Mowat-Wilson syndrome, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Stromme syndrome, Johanson-Blizzard syndrome, Kapur-Toriello syndrome, oculocerebrofacial syndrome, Kaufman type, Keutel syndrome, Lambert syndrome, Laurence-Moon syndrome, intellectual disability-spasticity-ectrodactyly syndrome, prominent glabella-microcephaly-hypogenitalism syndrome, Marden-Walker syndrome, microcephaly-glomerulonephritis-marfanoid habitus syndrome, marfanoid habitus-autosomal recessive intellectual disability syndrome, McDonough syndrome, intellectual disability-dysmorphism-hypogonadism-diabetes mellitus syndrome, intellectual disability, Buenos-Aires type, microcephaly-cardiomyopathy syndrome, Say-Barber-Miller syndrome, microcephaly-cervical spine fusion anomalies syndrome, Jawad syndrome, lethal multiple pterygium syndrome, neurofaciodigitorenal syndrome, oculo-palato-cerebral syndrome, Oliver syndrome, lethal omphalocele-cleft palate syndrome, Peters plus syndrome, Pfeiffer-Palm-Teller syndrome, urban-Rogers-Meyer syndrome, Wiedemann-Rautenstrauch syndrome, holoprosencephaly-postaxial polydactyly syndrome, radioulnar synostosis-developmental delay-hypotonia syndrome, Ulbright-Hodes syndrome, microbrachycephaly-ptosis-cleft lip syndrome, Smith-Lemli-Opitz syndrome, congenital heart defect-round face-developmental delay syndrome, Filippi syndrome, upper limb defect-eye and ear abnormalities syndrome, Weaver syndrome, intellectual disability, Wolff type, CHIME syndrome, X-linked intellectual disability-plagiocephaly syndrome, 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, creatine transporter deficiency, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, chromosome Xp11.23-p11.22 duplication syndrome, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, SSR4-congenital disorder of glycosylation, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability-balding-patella luxation-acromicria syndrome, syndromic X-linked intellectual disability 5, male hypergonadotropic hypogonadism-intellectual disability-skeletal anomalies syndrome, X-linked intellectual disability with marfanoid habitus, N syndrome, pterygium colli-intellectual disability-digital anomalies syndrome, Lowry-MacLean syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, pseudoaminopterin syndrome, acrocardiofacial syndrome, Ayme-Gripp syndrome, Harrod syndrome, fallot complex-intellectual disability-growth delay syndrome, MMEP syndrome, epilepsy-microcephaly-skeletal dysplasia syndrome, Fine-Lubinsky syndrome, intellectual disability-sparse hair-brachydactyly syndrome, colobomatous microphthalmia - obesity - hypogenitalism - intellectual disability syndrome, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, Wiedemann-Steiner syndrome, cerebrooculonasal syndrome, genitopatellar syndrome, intellectual disability-obesity-prognathism-eye and skin anomalies syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, AICA-ribosiduria, Goldberg-Shprintzen syndrome, complex cortical dysplasia with other brain malformations 7, Kleefstra syndrome, Koolen-de Vries syndrome, agammaglobulinemia-microcephaly-craniosynostosis-severe dermatitis syndrome, mandibulofacial dysostosis-microcephaly syndrome, camptodactyly syndrome, Guadalajara type 3, chromosome 15q13.3 microdeletion syndrome, chromosome 6pter-p24 deletion syndrome, Zechi-Ceide syndrome, chromosome 19q13.11 deletion syndrome, chromosome 5p13 duplication syndrome, chromosome 17p13.3 duplication syndrome, syndromic multisystem autoimmune disease due to ITCH deficiency, chromosome 15q24 deletion syndrome, chromosome 17q21.31 duplication syndrome, chromosome 19p13.13 deletion syndrome, THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome, DYRK1A-related intellectual disability syndrome, chromosome 8q21.11 deletion syndrome, microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome, chromosome 16q22 deletion syndrome, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, short ulna-dysmorphism-hypotonia-intellectual disability syndrome, microcephaly-intellectual disability-phalangeal and neurological anomalies syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, Hartsfield-Bixler-Demyer syndrome, developmental and epileptic encephalopathy, 18, severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome, CTCF-related neurodevelopmental disorder, severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome, 8q24.3 microdeletion syndrome, microcephaly-thin corpus callosum-intellectual disability syndrome, macrocephaly-developmental delay syndrome, chromosome 5q12 deletion syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Tatton-Brown-Rahman overgrowth syndrome, orofaciodigital syndrome type 14, Catel-Manzke syndrome, cerebellar-facial-dental syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, Houge-Janssens syndrome 2, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, hypomyelinating leukodystrophy 10, congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome, palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, 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, TELO2-related intellectual disability-neurodevelopmental disorder, transketolase deficiency, severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, tall stature-intellectual disability-renal anomalies syndrome, ZTTK syndrome, short stature-brachydactyly-obesity-global developmental delay syndrome, mucopolysaccharidosis-plus syndrome, hypotonia, ataxia, and delayed development syndrome, caudal appendage-deafness syndrome, arachnodactyly-abnormal ossification-intellectual disability syndrome, ataxia-photosensitivity-short stature syndrome, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, brachydactyly-mesomelia-intellectual disability-heart defects syndrome, cardiofaciocutaneous syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, Coffin-Siris syndrome, intellectual disability-hypoplastic corpus callosum-preauricular tag syndrome, craniodigital syndrome-intellectual disability syndrome, cryptorchidism-arachnodactyly-intellectual disability syndrome, facial dysmorphism-shawl scrotum-joint laxity syndrome, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, Cornelia de Lange syndrome, cleft palate-short stature-vertebral anomalies syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, holoprosencephaly, dysmorphism-short stature-deafness-disorder of sex development syndrome, 5q14.3 microdeletion syndrome, Kabuki syndrome, ptosis-syndactyly-learning difficulties syndrome, macrocephaly-short stature-paraplegia syndrome, Warburg micro syndrome, microcephaly-seizures-intellectual disability-heart disease syndrome, microcephaly-cleft palate syndrome, microcephaly-microcornea syndrome, Seemanova type, multiple congenital anomalies due to 14q32.2 maternally expressed gene defect, neuroectodermal-endocrine syndrome, Opitz G/BBB syndrome, Xp22.13p22.2 duplication syndrome, short stature-webbed neck-heart disease syndrome, microtriplication 11q24.1, preaxial polydactyly-colobomata-intellectual disability syndrome, blepharophimosis - intellectual disability syndrome, 3MC syndrome, Baraitser-Winter cerebrofrontofacial syndrome, 11p15.4 microduplication syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, intellectual disability-short stature-hypertelorism syndrome, intellectual disability-polydactyly-uncombable hair syndrome, 20p13 microdeletion syndrome, 7p22.1 microduplication syndrome, intellectual disability-hypotonia-brachycephaly-pyloric stenosis-cryptorchidism syndrome, 15q overgrowth syndrome, van Maldergem syndrome, distal 17p13.1 microdeletion syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, muscular hypertrophy-hepatomegaly-polyhydramnios syndrome, aphonia-deafness-retinal dystrophy-bifid halluces-intellectual disability syndrome, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, telecanthus-hypertelorism-strabismus-pes cavus syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Weaver-Williams syndrome, 20q11.2 microduplication syndrome, 2p13.2 microdeletion syndrome, intellectual disability-seizures-macrocephaly-obesity syndrome, intellectual disability-facial dysmorphism-hand anomalies syndrome, XYLT1-congenital disorder of glycosylation, 3q27.3 microdeletion syndrome, 9q31.1q31.3 microdeletion syndrome, 14q24.1q24.3 microdeletion syndrome, FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome, 13q12.3 microdeletion syndrome, cono-spondylar dysplasia, microcephaly-short stature-intellectual disability-facial dysmorphism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, 11q22.2q22.3 microdeletion syndrome, 20q11.2 microdeletion syndrome, 19p13.3 microduplication syndrome, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, 1p35.2 microdeletion syndrome, megalencephaly-severe kyphoscoliosis-overgrowth syndrome, intellectual disability-muscle weakness-short stature-facial dysmorphism syndrome, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, corpus callosum agenesis-macrocephaly-hypertelorism syndrome, DeSanto-Shinawi syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, Ritscher-Schinzel syndrome, visceral neuropathy-brain anomalies-facial dysmorphism-developmental delay syndrome, brain malformation-congenital heart disease-postaxial polydactyly 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, osteopenia-myopia-hearing loss-intellectual disability-facial dysmorphism syndrome, severe intellectual disability-epilepsy-anal anomalies-distal phalangeal hypoplasia, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, developmental and epileptic encephalopathy, 73, pancreatic agenesis-holoprosencephaly syndrome, oculocerebrodental syndrome, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, KAT6B-related multiple congenital anomalies syndrome, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 16p12.1p12.3 triplication syndrome, 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, early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, Gabriele de Vries syndrome, Skraban-Deardorff syndrome, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, Pilarowski-Bjornsson syndrome, glycosylphosphatidylinositol biosynthesis defect 15, multiple congenital anomalies-hypotonia-seizures syndrome, mesomelic dysplasia-digital anomalies-intellectual disability syndrome, KDM3B-related intellectual disability-facial dysmorphism-short stature syndrome, SLC12A2-related developmental delay-intellectual disability-sensorineural deafness syndrome, intellectual disability-early-onset cataract-microcephaly syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, PRC-2 complex-related overgrowth spectrum, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, severe congenital myelofibrosis-pancytopenia-intellectual disability-neurologic and ophthalmic abnormalities syndrome, progressive hypotonia-intellectual disability-facial dysmorphism syndrome due to FYVE-defective RBSN, intellectual disability-epilepsy-dental anomalies-facial dysmorphism syndrome, 2q13 microdeletion syndrome, 10p13-p14 deletion syndrome, 3q26q28 deletion syndrome, Pitt-Hopkins or Pitt-Hopkins-like syndrome, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, Martsolf syndrome 1

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 5 · 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
LIG4	Supportive	Autosomal recessive	Dubowitz syndrome	6
NSUN2	Supportive	Autosomal recessive	Dubowitz syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NSUN2	Orphanet:235	Dubowitz syndrome
NSUN2	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
LIG4	Orphanet:235	Dubowitz syndrome
LIG4	Orphanet:39041	Omenn syndrome
LIG4	Orphanet:99812	LIG4 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
NSUN2	HGNC:25994	ENSG00000037474	Q08J23	RNA cytosine C(5)-methyltransferase NSUN2	gencc
LIG4	HGNC:6601	ENSG00000174405	P49917	DNA ligase 4	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NSUN2	RNA cytosine C(5)-methyltransferase NSUN2	RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs).
LIG4	DNA ligase 4	DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	2	12.0×	0.007

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NSUN2	Enzyme (other)	yes	2.1.1.202	MeTrfase_RsmB-F_NOP2_dom, RCMT, RCMT_NCL1
LIG4	Enzyme (other)	yes	6.5.1.1	DNA_ligase_ATP-dep, BRCT_dom, DNA_ligase_ATP-dep_N

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
secondary oocyte	2
right uterine tube	1
upper arm skin	1
endothelial cell	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NSUN2	260	ubiquitous	marker	upper arm skin, right uterine tube, secondary oocyte
LIG4	275	ubiquitous	yes	endothelial cell, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NSUN2	3,213
LIG4	2,352

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LIG4	P49917	31
NSUN2	Q08J23	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
2-LTR circle formation	1	815.7×	0.004	LIG4
tRNA modification in the nucleus and cytosol	1	146.4×	0.010	NSUN2
Nonhomologous End-Joining (NHEJ)	1	84.0×	0.012	LIG4

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
meiotic cell cycle checkpoint signaling	1	8426.0×	0.002	NSUN2
establishment of integrated proviral latency	1	8426.0×	0.002	LIG4
positive regulation of chromosome organization	1	4213.0×	0.002	LIG4
pro-B cell differentiation	1	2106.5×	0.002	LIG4
T cell receptor V(D)J recombination	1	2106.5×	0.002	LIG4
tRNA stabilization	1	2106.5×	0.002	NSUN2
DN2 thymocyte differentiation	1	2106.5×	0.002	LIG4
in utero embryonic development	2	72.0×	0.002	NSUN2, LIG4
cell division	2	46.2×	0.002	NSUN2, LIG4
nucleotide-excision repair, DNA gap filling	1	1404.3×	0.003	LIG4
immunoglobulin V(D)J recombination	1	1404.3×	0.003	LIG4
regulation of mRNA export from nucleus	1	1053.2×	0.003	NSUN2
V(D)J recombination	1	1053.2×	0.003	LIG4
hair follicle maturation	1	1053.2×	0.003	NSUN2
double-strand break repair via classical nonhomologous end joining	1	842.6×	0.003	LIG4
single strand break repair	1	702.2×	0.004	LIG4
cellular response to lithium ion	1	561.7×	0.004	LIG4
response to X-ray	1	443.5×	0.005	LIG4
isotype switching	1	421.3×	0.005	LIG4
DNA biosynthetic process	1	401.2×	0.005	LIG4
regulation of stem cell differentiation	1	383.0×	0.005	NSUN2
tRNA modification	1	300.9×	0.006	NSUN2
response to gamma radiation	1	290.6×	0.006	LIG4
tRNA methylation	1	290.6×	0.006	NSUN2
positive regulation of neurogenesis	1	290.6×	0.006	LIG4
chromosome organization	1	290.6×	0.006	LIG4
base-excision repair	1	234.1×	0.007	LIG4
double-strand break repair via nonhomologous end joining	1	210.7×	0.007	LIG4
T cell differentiation in thymus	1	205.5×	0.007	LIG4
cellular response to ionizing radiation	1	205.5×	0.007	LIG4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NSUN2	1	2
LIG4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	NSUN2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
NSUN2	11	Binding:11
LIG4	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NSUN2	2.1.1.202, 2.1.1.203	multisite-specific tRNA:(cytosine-C5)-methyltransferase, tRNA (cytosine34-C5)-methyltransferase
LIG4	6.5.1.1	DNA ligase (ATP)

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

1 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)
MOLIBRESIB	2	NSUN2

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	1	NSUN2
C	Druggable family + PDB, no drug	1	LIG4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LIG4	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.