Transketolase deficiency

Summary

Transketolase deficiency (MONDO:0014881) is a disease caused by TKT (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TKT (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 20
• Phenotypes (HPO): 27

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001627	Abnormal heart morphology	Very frequent (80-99%)
HP:0003508	Proportionate short stature	Very frequent (80-99%)
HP:0025550	Elevated circulating ribitol concentration	Very frequent (80-99%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000554	Uveitis	Frequent (30-79%)
HP:0000722	Compulsive behaviors	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001256	Intellectual disability, mild	Frequent (30-79%)
HP:0001344	Absent speech	Frequent (30-79%)
HP:0001629	Ventricular septal defect	Frequent (30-79%)
HP:0001631	Atrial septal defect	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0410072	Increased level of ribose in urine	Frequent (30-79%)
HP:0000107	Renal cyst	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000509	Conjunctivitis	Occasional (5-29%)
HP:0000733	Abnormal repetitive mannerisms	Occasional (5-29%)
HP:0000869	Secondary amenorrhea	Occasional (5-29%)
HP:0001051	Seborrheic dermatitis	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001655	Patent foramen ovale	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0011686	Abnormal coronary artery course	Occasional (5-29%)
HP:0100651	Type I diabetes mellitus	Occasional (5-29%)
HP:0100716	Self-injurious behavior	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	transketolase deficiency
Mondo ID	MONDO:0014881
OMIM	617044
Orphanet	488618
UMLS	C5700245
MedGen	1814561
GARD	0017894
Is cancer (heuristic)	no

Also known as: SDDHD · short stature-developmental delay-congenital heart defect syndrome · TKT deficiency

Data availability: 20 ClinVar variants · 3 GenCC gene-disease records.

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 › transketolase deficiency

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, Dubowitz 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, 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

ClinVar germline variants

20 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 6 benign, 2 conflicting classifications of pathogenicity, 2 pathogenic, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
223089	NM_001064.4(TKT):c.633G>A (p.Trp211Ter)	TKT	Pathogenic	no assertion criteria provided
223091	NM_001064.4(TKT):c.952C>T (p.Arg318Cys)	TKT	Pathogenic	no assertion criteria provided
243092	NM_001135055.2:c.769_770insCTACCTCCTTATCTTCTG	TKT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3235058	NM_001064.4(TKT):c.181C>T (p.Gln61Ter)	TKT	Likely pathogenic	criteria provided, single submitter
4277802	NM_001064.4(TKT):c.1697-1G>A	TKT	Likely pathogenic	criteria provided, single submitter
1319301	NM_001064.4(TKT):c.1177T>C (p.Phe393Leu)	TKT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
777965	NM_001064.4(TKT):c.541A>G (p.Ile181Val)	TKT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033727	NM_001064.4(TKT):c.1540G>A (p.Glu514Lys)	LOC126806684	Uncertain significance	criteria provided, single submitter
2441738	NM_001064.4(TKT):c.1136G>A (p.Arg379His)	TKT	Uncertain significance	criteria provided, single submitter
2441997	NM_001064.4(TKT):c.1604T>A (p.Phe535Tyr)	TKT	Uncertain significance	criteria provided, single submitter
3589470	NM_001064.4(TKT):c.458T>C (p.Leu153Pro)	TKT	Uncertain significance	criteria provided, multiple submitters, no conflicts
3780951	NM_001064.4(TKT):c.*3C>T	TKT	Uncertain significance	criteria provided, single submitter
3969134	NM_001064.4(TKT):c.605A>G (p.Tyr202Cys)	TKT	Uncertain significance	criteria provided, multiple submitters, no conflicts
4291787	NM_001064.4(TKT):c.628G>T (p.Gly210Cys)	TKT	Uncertain significance	criteria provided, single submitter
1342213	NM_001064.4(TKT):c.1697-49C>T	TKT	Benign	criteria provided, multiple submitters, no conflicts
1342214	NM_001064.4(TKT):c.1265-47G>C	TKT	Benign	criteria provided, multiple submitters, no conflicts
1342215	NM_001064.4(TKT):c.1264+17T>C	TKT	Benign	criteria provided, multiple submitters, no conflicts
1342216	NM_001064.4(TKT):c.749-15G>A	TKT	Benign	criteria provided, multiple submitters, no conflicts
1342217	NM_001064.4(TKT):c.748+39C>G	TKT	Benign	criteria provided, multiple submitters, no conflicts
1342218	NM_001064.4(TKT):c.748+17C>T	TKT	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DDR2	Strong	Autosomal recessive	transketolase deficiency	13
TKT	Strong	Autosomal recessive	transketolase deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TKT	Orphanet:488618	Transketolase deficiency
DDR2	Orphanet:93358	Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification 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
TKT	HGNC:11834	ENSG00000163931	P29401	Transketolase	gencc,clinvar
DDR2	HGNC:2731	ENSG00000162733	Q16832	Discoidin domain-containing receptor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TKT	Transketolase	Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.
DDR2	Discoidin domain-containing receptor 2	Tyrosine kinase involved in the regulation of tissues remodeling.

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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TKT	Enzyme (other)	yes	2.2.1.1	Transketolase_N, Transketolase-like_Pyr-bd, Transketo_C/PFOR_II
DDR2	Kinase	yes	2.7.10.1	FA58C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

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
leukocyte	1
monocyte	1
mononuclear cell	1
cauda epididymis	1
tendon of biceps brachii	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TKT	301	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
DDR2	270	ubiquitous	marker	cauda epididymis, tendon of biceps brachii, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TKT	4,277
DDR2	1,575

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TKT	P29401	13
DDR2	Q16832	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Insulin effects increased synthesis of Xylulose-5-Phosphate	1	2855.0×	0.001	TKT
NFE2L2 regulates pentose phosphate pathway genes	1	713.8×	0.003	TKT
Pentose phosphate pathway	1	475.8×	0.003	TKT
Non-integrin membrane-ECM interactions	1	77.2×	0.013	DDR2

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
D-xylulose 5-phosphate biosynthetic process	1	8426.0×	0.004	TKT
positive regulation of hepatic stellate cell proliferation	1	2808.7×	0.004	DDR2
glyceraldehyde-3-phosphate biosynthetic process	1	2106.5×	0.004	TKT
negative regulation of hydrogen peroxide-mediated programmed cell death	1	2106.5×	0.004	DDR2
regulation of extracellular matrix disassembly	1	1685.2×	0.004	DDR2
pentose-phosphate shunt, non-oxidative branch	1	1404.3×	0.004	TKT
positive regulation of hepatic stellate cell activation	1	1404.3×	0.004	DDR2
regulation of tissue remodeling	1	1053.2×	0.005	DDR2
endochondral bone growth	1	842.6×	0.005	DDR2
pentose-phosphate shunt	1	766.0×	0.005	TKT
collagen-activated tyrosine kinase receptor signaling pathway	1	648.1×	0.005	DDR2
positive regulation of extracellular matrix disassembly	1	601.9×	0.005	DDR2
positive regulation of fibroblast migration	1	561.7×	0.005	DDR2
chondrocyte proliferation	1	526.6×	0.005	DDR2
positive regulation of vascular associated smooth muscle cell migration	1	495.6×	0.005	DDR2
regulation of growth	1	468.1×	0.005	TKT
cellular response to angiotensin	1	468.1×	0.005	DDR2
response to muscle stretch	1	383.0×	0.006	DDR2
regulation of bone mineralization	1	366.4×	0.006	DDR2
positive regulation of protein kinase activity	1	337.0×	0.006	DDR2
biomineral tissue development	1	324.1×	0.006	DDR2
positive regulation of collagen biosynthetic process	1	324.1×	0.006	DDR2
obsolete positive regulation of DNA-binding transcription factor activity	1	300.9×	0.006	DDR2
positive regulation of wound healing	1	263.3×	0.006	DDR2
positive regulation of vascular associated smooth muscle cell proliferation	1	216.1×	0.007	DDR2
peptidyl-tyrosine phosphorylation	1	210.7×	0.007	DDR2
positive regulation of G1/S transition of mitotic cell cycle	1	200.6×	0.008	DDR2
positive regulation of fibroblast proliferation	1	147.8×	0.010	DDR2
cellular response to transforming growth factor beta stimulus	1	138.1×	0.010	DDR2
ossification	1	113.9×	0.011	DDR2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
DDR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDR2	59	4
TKT	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	DDR2
FEDRATINIB	4	DDR2
TIVOZANIB	4	DDR2
LENVATINIB	4	DDR2
AXITINIB	4	DDR2
SORAFENIB	4	DDR2
DASATINIB ANHYDROUS	4	DDR2
DACTINOMYCIN	4	DDR2
REGORAFENIB	4	DDR2
CABOZANTINIB	4	DDR2
VANDETANIB	4	DDR2
NILOTINIB	4	DDR2
BOSUTINIB	4	DDR2
TOVORAFENIB	4	DDR2
PAZOPANIB	4	DDR2
NINTEDANIB	4	DDR2
SUNITINIB	4	DDR2
DASATINIB	4	DDR2
QUIZARTINIB	4	DDR2
IMATINIB	4	DDR2
MASITINIB	3	DDR2
SARACATINIB	3	DDR2
LINIFANIB	3	DDR2
TESEVATINIB	3	DDR2
NAPORAFENIB	3	DDR2
CEDIRANIB	3	DDR2
DOVITINIB	3	DDR2
LESTAURTINIB	3	DDR2
MOLIBRESIB	2	TKT
DORAMAPIMOD	2	DDR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
DDR2	389	Binding:386, ADMET:3
TKT	18	Binding:18

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TKT	2.2.1.1	transketolase
DDR2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
DDR2	389

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

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)
PONATINIB	4	DDR2
FEDRATINIB	4	DDR2
TIVOZANIB	4	DDR2
LENVATINIB	4	DDR2
AXITINIB	4	DDR2
SORAFENIB	4	DDR2
DASATINIB ANHYDROUS	4	DDR2
DACTINOMYCIN	4	DDR2
REGORAFENIB	4	DDR2
CABOZANTINIB	4	DDR2
VANDETANIB	4	DDR2
NILOTINIB	4	DDR2
BOSUTINIB	4	DDR2
TOVORAFENIB	4	DDR2
PAZOPANIB	4	DDR2
NINTEDANIB	4	DDR2
SUNITINIB	4	DDR2
DASATINIB	4	DDR2
QUIZARTINIB	4	DDR2
IMATINIB	4	DDR2
MASITINIB	3	DDR2
SARACATINIB	3	DDR2
LINIFANIB	3	DDR2
TESEVATINIB	3	DDR2
NAPORAFENIB	3	DDR2
CEDIRANIB	3	DDR2
DOVITINIB	3	DDR2
LESTAURTINIB	3	DDR2
MOLIBRESIB	2	TKT
DORAMAPIMOD	2	DDR2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DDR2
B	Phased (≥1) drug, not yet approved	1	TKT
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.