HOS
MCID: HLT001
MIFTS: 63

Holt-Oram Syndrome (HOS)

Categories: Bone diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Holt-Oram Syndrome

MalaCards integrated aliases for Holt-Oram Syndrome:

Name: Holt-Oram Syndrome 58 12 77 25 54 26 76 38 30 13 56 6 45 15 41 74
Hos 58 54 26 76 17
Atriodigital Dysplasia 58 12 54 26
Heart-Hand Syndrome 58 12 54
Heart-Hand Syndrome, Type 1 54 26
Ventriculo-Radial Syndrome 54 26
Atrio-Digital Syndrome 12 26
Cardiac-Limb Syndrome 54 26
Atrio Digital Syndrome 54
Hearthand Syndrome 25
Holt Oram Syndrome 56
Hos 1 54
Hos1 58

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant


HPO:

33
holt-oram syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance The upper-limb malformations in hos are fully penetrant...

Classifications:



Summaries for Holt-Oram Syndrome

NIH Rare Diseases : 54 Holt-Oram syndrome affects the bones of the hands and arms and may also affect the heart. People with Holt-Oram syndrome have at least one bone in the wrist that did not form (develop) normally. Other bones in the hands, arms, and shoulder may also have developed abnormally. Many of these developmental changes in the bones can only be seen on an x-ray. Most people with Holt-Oram syndrome also have heart problems, including problems due to the way the heart formed (congenital) or problems with the way the heart beats.Holt-Oram syndrome is caused by genetic changes (pathogenic variants or mutations) in the TBX5 gene. The syndrome is inherited in an autosomal dominant manner. A diagnosis of Holt-Oram syndrome may be suspected when a person has symptoms of the syndrome. An x-ray of the hands, wrists, and arms, echocardiogram of the heart, and genetic testing may be used to confirm the diagnosis. Treatment options for Holt-Oram syndrome may include surgeries to treat bone or heart problems, as well as physical therapy. 

MalaCards based summary : Holt-Oram Syndrome, also known as hos, is related to duane-radial ray syndrome and left ventricular noncompaction. An important gene associated with Holt-Oram Syndrome is TBX5 (T-Box 5), and among its related pathways/superpathways are NFAT and Cardiac Hypertrophy and Cardiac conduction. The drugs Doxorubicin and Doxil have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and testes, and related phenotypes are joint stiffness and split hand

Disease Ontology : 12 An autosomal dominant disease characterized by congenital anomalies located in heart and located in upper limb.

Genetics Home Reference : 26 Holt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems.

OMIM : 58 Holt-Oram syndrome is an autosomal dominant disorder characterized by abnormalities of the upper limbs and shoulder girdle, associated with a congenital heart lesion. The typical combination is considered to be a triphalangeal thumb with a secundum atrial septal defect (ASD), but there is a great range in the severity of both the heart and skeletal lesions (summary by Hurst et al., 1991). (142900)

UniProtKB/Swiss-Prot : 76 Holt-Oram syndrome: Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects.

Wikipedia : 77 Holt–Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome,... more...

GeneReviews: NBK1111

Related Diseases for Holt-Oram Syndrome

Diseases related to Holt-Oram Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 79)
# Related Disease Score Top Affiliating Genes
1 duane-radial ray syndrome 32.5 SALL4 TBX5
2 left ventricular noncompaction 30.3 MYH6 MYH7 NKX2-5
3 atrial heart septal defect 30.1 TBX5 NKX2-5 MYH6 GATA4
4 ventricular septal defect 30.0 TBX5 NKX2-5 MYH7 GATA4
5 tetralogy of fallot 29.9 TBX5 TBX1 NKX2-5 GATA4
6 double outlet right ventricle 29.9 TBX1 NKX2-5 GATA4
7 heart disease 29.2 TBX5 TBX1 NKX2-5 MYH7 MYH6 GATA4
8 dilated cardiomyopathy 28.8 TGFB2 TBX5 NKX2-5 MYH7 MYH6 GATA4
9 heart-hand syndrome, slovenian type 12.6
10 heart-hand syndrome, spanish type 12.5
11 tabatznik syndrome 11.7
12 polydactyly, preaxial ii 11.5
13 long-thumb brachydactyly syndrome 11.0
14 polydactyly 10.5
15 atrial fibrillation 10.5
16 central polydactyly 10.5
17 hypoplastic left heart syndrome 1 10.4
18 hypoplastic left heart syndrome 10.4
19 fetal thalidomide syndrome 10.4
20 horns in sheep 10.4
21 murcs association 10.3 TBX5 TBX3
22 heart, malformation of 10.3 TBX5 MYH6
23 acheiropody 10.3 TBX3 TBX5
24 kleine-levin hibernation syndrome 10.2
25 monilethrix 10.2
26 pheochromocytoma 10.2
27 prostate cancer 10.2
28 duodenal atresia 10.2
29 lung agenesis 10.2
30 lung agenesis, congenital heart defects, and thumb anomalies syndrome 10.2
31 prostate cancer, hereditary, 8 10.2
32 patent ductus arteriosus 1 10.2
33 prostate cancer, hereditary, 6 10.2
34 pulmonary hypertension 10.2
35 crohn's disease 10.2
36 osteonecrosis 10.2
37 malignant pheochromocytoma 10.2
38 microcephaly 10.2
39 myopia 10.2
40 malignant hyperthermia 10.2
41 lymphosarcoma 10.2
42 rere-related disorders 10.2
43 aortic coarctation 10.2
44 aortopulmonary window 10.2
45 syncope 10.2
46 radial hemimelia 10.2
47 double-orifice mitral valve 10.2
48 sinoatrial node disease 10.2 MYH6 TBX3
49 pulmonary valve disease 10.1 GATA4 TBX5
50 ovarian endodermal sinus tumor 10.1 NKX2-5 SALL4

Graphical network of the top 20 diseases related to Holt-Oram Syndrome:



Diseases related to Holt-Oram Syndrome

Symptoms & Phenotypes for Holt-Oram Syndrome

Human phenotypes related to Holt-Oram Syndrome:

33 (show all 44)
# Description HPO Frequency HPO Source Accession
1 joint stiffness 33 hallmark (90%) HP:0001387
2 split hand 33 hallmark (90%) HP:0001171
3 abnormality of the clavicle 33 hallmark (90%) HP:0000889
4 scoliosis 33 frequent (33%) HP:0002650
5 kyphosis 33 frequent (33%) HP:0002808
6 atrial septal defect 33 frequent (33%) HP:0001631
7 first degree atrioventricular block 33 frequent (33%) HP:0011705
8 abnormality of the metacarpal bones 33 frequent (33%) HP:0001163
9 ventricular septal defect 33 very rare (1%) HP:0001629
10 triphalangeal thumb 33 very rare (1%) HP:0001199
11 aplasia/hypoplasia of the radius 33 frequent (33%) HP:0006501
12 absent thumb 33 very rare (1%) HP:0009777
13 paroxysmal atrial fibrillation 33 frequent (33%) HP:0004757
14 pectus excavatum 33 very rare (1%) HP:0000767
15 finger syndactyly 33 occasional (7.5%) HP:0006101
16 broad thumb 33 occasional (7.5%) HP:0011304
17 patent ductus arteriosus 33 very rare (1%) HP:0001643
18 hypoplastic left heart 33 occasional (7.5%) HP:0004383
19 sprengel anomaly 33 occasional (7.5%) HP:0000912
20 abnormality of the ribs 33 occasional (7.5%) HP:0000772
21 radioulnar synostosis 33 occasional (7.5%) HP:0002974
22 down-sloping shoulders 33 occasional (7.5%) HP:0200021
23 atrioventricular canal defect 33 occasional (7.5%) HP:0006695
24 abnormal aortic morphology 33 occasional (7.5%) HP:0001679
25 phocomelia 33 occasional (7.5%) HP:0009829
26 abnormality of the humerus 33 occasional (7.5%) HP:0003063
27 anomalous pulmonary venous return 33 occasional (7.5%) HP:0010772
28 hypoplasia of the ulna 33 very rare (1%) HP:0003022
29 finger clinodactyly 33 very rare (1%) HP:0040019
30 secundum atrial septal defect 33 very rare (1%) HP:0001684
31 hypoplasia of the radius 33 very rare (1%) HP:0002984
32 short clavicles 33 very rare (1%) HP:0000894
33 aplasia of the pectoralis major muscle 33 very rare (1%) HP:0009751
34 absent radius 33 very rare (1%) HP:0003974
35 limited elbow extension 33 very rare (1%) HP:0001377
36 syndactyly 33 very rare (1%) HP:0001159
37 short humerus 33 very rare (1%) HP:0005792
38 small thenar eminence 33 very rare (1%) HP:0001245
39 short digit 33 very rare (1%) HP:0011927
40 aplasia of the ulna 33 very rare (1%) HP:0003982
41 abnormal vertebral morphology 33 HP:0003468
42 partial duplication of thumb phalanx 33 HP:0009944
43 thoracic scoliosis 33 HP:0002943
44 abnormality of the carpal bones 33 HP:0001191

Symptoms via clinical synopsis from OMIM:

58
Cardiovascular Vascular:
patent ductus arteriosus

Skeletal Limbs:
triphalangeal thumb
absent thumb
bifid thumb
carpal bone anomalies
upper extremity phocomelia
more
Chest External Features:
absent pectoralis major muscle

Cardiovascular Heart:
ventricular septal defect
hypoplastic left heart syndrome
atrial septal defect (ostium secundum type)

Skeletal Spine:
thoracic scoliosis
vertebral anomalies

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum or carinatum

Clinical features from OMIM:

142900

GenomeRNAi Phenotypes related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased Aire reporter expression GR00304-A 8.8 NKX2-5 SALL4 TBX3

MGI Mouse Phenotypes related to Holt-Oram Syndrome:

47 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.25 EP300 GATA4 MYH6 MYH7 NKX2-5 SALL4
2 embryo MP:0005380 10.11 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX1
3 growth/size/body region MP:0005378 10.06 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX1
4 digestive/alimentary MP:0005381 10.02 EP300 GATA4 NKX2-5 SALL4 TBX1 TBX3
5 homeostasis/metabolism MP:0005376 10.02 EP300 GATA4 MYH6 NKX2-5 SALL4 TBX1
6 mortality/aging MP:0010768 10 EP300 GATA4 KAT2B MYH6 NKX2-5 SALL4
7 endocrine/exocrine gland MP:0005379 9.98 EP300 GATA4 NKX2-5 SRSF2 TBX1 TBX3
8 craniofacial MP:0005382 9.97 EP300 NKX2-5 SALL4 TBX1 TBX3 TGFB2
9 muscle MP:0005369 9.85 EP300 GATA4 MYH6 MYH7 NKX2-5 SRSF2
10 limbs/digits/tail MP:0005371 9.8 GATA4 SALL4 TBX1 TBX3 TBX5 TGFB2
11 normal MP:0002873 9.5 EP300 GATA4 KAT2B NKX2-5 TBX1 TBX3
12 respiratory system MP:0005388 9.1 EP300 GATA4 MYH6 NKX2-5 TBX1 TGFB2

Drugs & Therapeutics for Holt-Oram Syndrome

Drugs for Holt-Oram Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Doxorubicin Approved, Investigational Phase 2 23214-92-8 31703
2
Doxil Approved June 1999 Phase 2 31703
3 Anti-Bacterial Agents Phase 2
4 Topoisomerase Inhibitors Phase 2
5 Antibiotics, Antitubercular Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Doxil in the Treatment of Patients With Refractory Idiopathic Thrombocytopenic Purpura Unknown status NCT00107913 Phase 2 Doxil

Search NIH Clinical Center for Holt-Oram Syndrome

Cochrane evidence based reviews: holt-oram syndrome

Genetic Tests for Holt-Oram Syndrome

Genetic tests related to Holt-Oram Syndrome:

# Genetic test Affiliating Genes
1 Holt-Oram Syndrome 30 TBX5

Anatomical Context for Holt-Oram Syndrome

MalaCards organs/tissues related to Holt-Oram Syndrome:

42
Heart, Bone, Testes, Skin, Prostate, T Cells, Nk Cells

The Foundational Model of Anatomy Ontology organs/tissues related to Holt-Oram Syndrome:

20
Heart, Upper Limb

Publications for Holt-Oram Syndrome

Articles related to Holt-Oram Syndrome:

(show top 50) (show all 281)
# Title Authors Year
1
Possible Holt-Oram Syndrome: Missed Prenatal Diagnosis and Sub-Optimal Management in a Poor-Resourced Hospital ( 30873826 )
2019
2
Holt-Oram syndrome: clinical and molecular description of 78 patients with TBX5 variants. ( 30552424 )
2019
3
miR-142-5p suppresses proliferation and promotes apoptosis of human osteosarcoma cell line, HOS, by targeting PLA2G16 through the ERK1/2 signaling pathway. ( 30655907 )
2019
4
Highly-expressed P2X7 receptor promotes growth and metastasis of human HOS/MNNG osteosarcoma cells via PI3K/Akt/GSK3β/β-catenin and mTOR/HIF1α/VEGF signaling. ( 30761524 )
2019
5
Holt-Oram syndrome in two families diagnosed with left ventricular noncompaction and conduction disease. ( 29755943 )
2018
6
Genetic Analyses Identified a SALL4 Gene Mutation Associated with Holt-Oram Syndrome. ( 29461882 )
2018
7
Holt-Oram Syndrome in a Patient with Crohn's Disease: a Rare Case Report and Literature Review. ( 30514998 )
2018
8
An Unusual Finding of a Double Orifice Mitral Valve in a Patient With Holt-Oram Syndrome. ( 30555010 )
2018
9
Holt-Oram Syndrome With Multiple Cardiac Abnormalities. ( 30344832 )
2018
10
A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome. ( 30538526 )
2018
11
Intrafamilial variability in the clinical manifestations of mucopolysaccharidosis type II: Data from the Hunter Outcome Survey (HOS). ( 29210515 )
2018
12
Clinical characteristics and surgical history of Taiwanese patients with mucopolysaccharidosis type II: data from the hunter outcome survey (HOS). ( 29866148 )
2018
13
Measured and estimated data of non-linear BRAN channels using HOS in 4G wireless communications. ( 29876470 )
2018
14
Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells. ( 30106429 )
2018
15
Cantharidin Inhibits Anti-Apoptotic Bcl-2 Family Proteins and Induces Apoptosis in Human Osteosarcoma Cell Lines MG-63 and MNNG/HOS via Mitochondria-Dependent Pathway. ( 30248086 )
2018
16
Comparing the Performance of 2 Health Utility Measures in the Medicare Health Outcome Survey (HOS). ( 30403580 )
2018
17
Validation of the Brazilian version of the Hip Outcome Score (HOS) questionnaire. ( 30657066 )
2018
18
Holt-Oram Syndrome: A Rare Variant. ( 28761211 )
2017
19
KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. ( 28164238 )
2017
20
Holt-Oram syndrome: Anesthetic challenges and safe outcome. ( 28074809 )
2017
21
Ten years of the Hunter Outcome Survey (HOS): insights, achievements, and lessons learned from a global patient registry. ( 28464912 )
2017
22
Survival in idursulfase-treated and untreated patients with mucopolysaccharidosis type II: data from the Hunter Outcome Survey (HOS). ( 28887757 )
2017
23
Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS). ( 28974237 )
2017
24
Transdifferentiation of human MNNG/HOS osteosarcoma cells into vascular endothelial cells in vitro and in vivo. ( 29048647 )
2017
25
TBX5 loss-of-function mutation contributes to atrial fibrillation and atypical Holt-Oram syndrome. ( 27035640 )
2016
26
A novel mutated sequence in the T-box transcription factor-5 (TBX-5) gene (c.241A>T) in Holt-Oram syndrome. ( 27026770 )
2016
27
Coexisting urogenital anomaly and duodenal atresia in two atypical Holt-Oram syndrome. ( 27695215 )
2016
28
A "Sleeping Beauty" With a "Heart-Hand": Kleine-Levin Syndrome Treated With Buproprion and Carbamazepine in a Patient With Holt-Oram Syndrome. ( 27090505 )
2016
29
A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome leading to a dramatically reduced biological function. ( 27652283 )
2016
30
Holt-Oram syndrome because of the novel TBX5 mutation c.481A>C. ( 27552067 )
2016
31
Holt-Oram Syndrome Associated with Aortic Atresia: A Rare Association. ( 27293527 )
2016
32
Is there a link between Holt-Oram Syndrome and 'Mardini-Nyhan' association? - need for further research. ( 26990964 )
2016
33
Left Ventricular Non-compaction in Holt-Oram Syndrome. ( 26874791 )
2016
34
Absent Left Main Coronary Artery and Separate Ostia of Left Coronary System in a Patient with Holt-Oram Syndrome and Sinus Node Dysfunction. ( 26882979 )
2016
35
Holt Oram syndrome: a case report and review of the literature. ( 27048037 )
2016
36
Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis. ( 27958623 )
2016
37
Discovering miRNA Regulatory Networks in Holt-Oram Syndrome Using a Zebrafish Model. ( 27471727 )
2016
38
Syndromic anorectal malformation associated with Holt-Oram syndrome, microcephaly, and bilateral corneal opacity: a case report. ( 27495810 )
2016
39
Computer-aided diagnosis of psoriasis skin images with HOS, texture and color features: A first comparative study of its kind. ( 26830378 )
2016
40
The natural history of growth in patients with Hunter syndrome: Data from the Hunter Outcome Survey (HOS). ( 26846156 )
2016
41
Anticancer Activity Studies of Ruthenium(II) Complex Toward Human Osteosarcoma HOS Cells. ( 27007877 )
2016
42
An algorithm for space-time block code classification using higher-order statistics (HOS). ( 27186481 )
2016
43
The effect of Me2SO overexposure during cryopreservation on HOS TE85 and hMSC viability, growth and quality. ( 27660063 )
2016
44
Tetralogy of Fallot with Holt-Oram syndrome: case report and review. ( 25903110 )
2015
45
A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome. ( 26780237 )
2015
46
Molecular basis of the clinical features of Holt-Oram syndrome resulting from missense and extended protein mutations of the TBX5 gene as well as TBX5 intragenic duplications. ( 25680289 )
2015
47
Horseshoe Lung Associated With Holt-Oram Syndrome. ( 26195995 )
2015
48
A novel missense mutation in the TBX5 gene in a Saudi infant with Holt-Oram syndrome. ( 26219450 )
2015
49
Defining Features of the Upper Extremity in Holt-Oram Syndrome. ( 26243320 )
2015
50
Monilethrix with holt-oram syndrome: case report of a rare association. ( 25878448 )
2015

Variations for Holt-Oram Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Holt-Oram Syndrome:

76
# Symbol AA change Variation ID SNP ID
1 TBX5 p.Arg237Gln VAR_007456 rs104894378
2 TBX5 p.Gly80Arg VAR_009701 rs104894381
3 TBX5 p.Arg237Trp VAR_009702 rs104894382
4 TBX5 p.Gln49Lys VAR_015381 rs104894383
5 TBX5 p.Ile54Thr VAR_015382 rs104894384

ClinVar genetic disease variations for Holt-Oram Syndrome:

6 (show top 50) (show all 273)
# Gene Variation Type Significance SNP ID Assembly Location
1 TBX5 NM_000192.3(TBX5): c.114C> T (p.Ser38=) single nucleotide variant Benign/Likely benign rs34014008 GRCh37 Chromosome 12, 114841590: 114841590
2 TBX5 NM_000192.3(TBX5): c.114C> T (p.Ser38=) single nucleotide variant Benign/Likely benign rs34014008 GRCh38 Chromosome 12, 114403785: 114403785
3 TGFB2 NM_003238.4(TGFB2): c.644-4C> T single nucleotide variant Conflicting interpretations of pathogenicity rs11466408 GRCh37 Chromosome 1, 218607676: 218607676
4 TGFB2 NM_003238.4(TGFB2): c.644-4C> T single nucleotide variant Conflicting interpretations of pathogenicity rs11466408 GRCh38 Chromosome 1, 218434334: 218434334
5 TBX5 NM_000192.3(TBX5): c.787G> A (p.Val263Met) single nucleotide variant Benign/Likely benign rs147405081 GRCh37 Chromosome 12, 114804165: 114804165
6 TBX5 NM_000192.3(TBX5): c.787G> A (p.Val263Met) single nucleotide variant Benign/Likely benign rs147405081 GRCh38 Chromosome 12, 114366360: 114366360
7 TGFB2 NM_001135599.3(TGFB2): c.114G> A (p.Glu38=) single nucleotide variant Benign/Likely benign rs149215818 GRCh38 Chromosome 1, 218346815: 218346815
8 TGFB2 NM_001135599.3(TGFB2): c.114G> A (p.Glu38=) single nucleotide variant Benign/Likely benign rs149215818 GRCh37 Chromosome 1, 218520157: 218520157
9 TGFB2 NM_003238.4(TGFB2): c.199G> A (p.Val67Met) single nucleotide variant Uncertain significance rs201761868 GRCh37 Chromosome 1, 218520242: 218520242
10 TGFB2 NM_003238.4(TGFB2): c.199G> A (p.Val67Met) single nucleotide variant Uncertain significance rs201761868 GRCh38 Chromosome 1, 218346900: 218346900
11 TGFB2 NM_003238.4(TGFB2): c.236A> G (p.Gln79Arg) single nucleotide variant Uncertain significance rs371241859 GRCh37 Chromosome 1, 218520279: 218520279
12 TGFB2 NM_003238.4(TGFB2): c.236A> G (p.Gln79Arg) single nucleotide variant Uncertain significance rs371241859 GRCh38 Chromosome 1, 218346937: 218346937
13 TGFB2 NM_001135599.3(TGFB2): c.272G> A (p.Arg91His) single nucleotide variant Conflicting interpretations of pathogenicity rs10482721 GRCh37 Chromosome 1, 218520315: 218520315
14 TGFB2 NM_001135599.3(TGFB2): c.272G> A (p.Arg91His) single nucleotide variant Conflicting interpretations of pathogenicity rs10482721 GRCh38 Chromosome 1, 218346973: 218346973
15 TGFB2 NM_001135599.3(TGFB2): c.440C> T (p.Pro147Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh37 Chromosome 1, 218578520: 218578520
16 TGFB2 NM_001135599.3(TGFB2): c.440C> T (p.Pro147Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh38 Chromosome 1, 218405178: 218405178
17 TGFB2 NM_001135599.3(TGFB2): c.441G> A (p.Pro147=) single nucleotide variant Benign/Likely benign rs138514914 GRCh37 Chromosome 1, 218578521: 218578521
18 TGFB2 NM_001135599.3(TGFB2): c.441G> A (p.Pro147=) single nucleotide variant Benign/Likely benign rs138514914 GRCh38 Chromosome 1, 218405179: 218405179
19 TGFB2 NM_003238.4(TGFB2): c.583G> T (p.Glu195Ter) single nucleotide variant Pathogenic rs863223790 GRCh37 Chromosome 1, 218607496: 218607496
20 TGFB2 NM_003238.4(TGFB2): c.583G> T (p.Glu195Ter) single nucleotide variant Pathogenic rs863223790 GRCh38 Chromosome 1, 218434154: 218434154
21 TGFB2 NM_003238.4(TGFB2): c.823A> G (p.Ser275Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs139825195 GRCh37 Chromosome 1, 218609380: 218609380
22 TGFB2 NM_003238.4(TGFB2): c.823A> G (p.Ser275Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs139825195 GRCh38 Chromosome 1, 218436038: 218436038
23 TGFB2 NM_003238.4(TGFB2): c.1239C> T (p.Cys413=) single nucleotide variant Benign/Likely benign rs141225367 GRCh38 Chromosome 1, 218441356: 218441356
24 TGFB2 NM_003238.4(TGFB2): c.1239C> T (p.Cys413=) single nucleotide variant Benign/Likely benign rs141225367 GRCh37 Chromosome 1, 218614698: 218614698
25 TBX5 NM_000192.3(TBX5): c.331G> T (p.Asp111Tyr) single nucleotide variant Benign/Likely benign rs77357563 GRCh37 Chromosome 12, 114837349: 114837349
26 TBX5 NM_000192.3(TBX5): c.331G> T (p.Asp111Tyr) single nucleotide variant Benign/Likely benign rs77357563 GRCh38 Chromosome 12, 114399544: 114399544
27 TBX5 NM_000192.3(TBX5): c.316A> G (p.Ile106Val) single nucleotide variant Benign/Likely benign rs147710408 GRCh38 Chromosome 12, 114399559: 114399559
28 TBX5 NM_000192.3(TBX5): c.316A> G (p.Ile106Val) single nucleotide variant Benign/Likely benign rs147710408 GRCh37 Chromosome 12, 114837364: 114837364
29 TBX5 NM_000192.3(TBX5): c.309C> T (p.Leu103=) single nucleotide variant Benign rs28730763 GRCh38 Chromosome 12, 114399566: 114399566
30 TBX5 NM_000192.3(TBX5): c.309C> T (p.Leu103=) single nucleotide variant Benign rs28730763 GRCh37 Chromosome 12, 114837371: 114837371
31 TBX5 TBX5, 1491C-T single nucleotide variant Pathogenic
32 TBX5 NM_000192.3(TBX5): c.205G> T (p.Glu69Ter) single nucleotide variant Pathogenic rs104894377 GRCh37 Chromosome 12, 114839668: 114839668
33 TBX5 NM_000192.3(TBX5): c.205G> T (p.Glu69Ter) single nucleotide variant Pathogenic rs104894377 GRCh38 Chromosome 12, 114401863: 114401863
34 TBX5 NM_000192.3(TBX5): c.710G> A (p.Arg237Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894378 GRCh37 Chromosome 12, 114823326: 114823326
35 TBX5 NM_000192.3(TBX5): c.710G> A (p.Arg237Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894378 GRCh38 Chromosome 12, 114385521: 114385521
36 TBX5 NM_000192.3(TBX5): c.238G> A (p.Gly80Arg) single nucleotide variant Pathogenic rs104894381 GRCh37 Chromosome 12, 114839635: 114839635
37 TBX5 NM_000192.3(TBX5): c.238G> A (p.Gly80Arg) single nucleotide variant Pathogenic rs104894381 GRCh38 Chromosome 12, 114401830: 114401830
38 TBX5 NM_000192.3(TBX5): c.709C> T (p.Arg237Trp) single nucleotide variant Pathogenic rs104894382 GRCh37 Chromosome 12, 114823327: 114823327
39 TBX5 NM_000192.3(TBX5): c.709C> T (p.Arg237Trp) single nucleotide variant Pathogenic rs104894382 GRCh38 Chromosome 12, 114385522: 114385522
40 TBX5 TBX5, 1-BP DEL, 416C deletion Pathogenic
41 TBX5 NM_000192.3(TBX5): c.145C> A (p.Gln49Lys) single nucleotide variant Pathogenic rs104894383 GRCh37 Chromosome 12, 114841559: 114841559
42 TBX5 NM_000192.3(TBX5): c.145C> A (p.Gln49Lys) single nucleotide variant Pathogenic rs104894383 GRCh38 Chromosome 12, 114403754: 114403754
43 TBX5 NM_000192.3(TBX5): c.161T> C (p.Ile54Thr) single nucleotide variant Pathogenic rs104894384 GRCh37 Chromosome 12, 114839712: 114839712
44 TBX5 NM_000192.3(TBX5): c.161T> C (p.Ile54Thr) single nucleotide variant Pathogenic rs104894384 GRCh38 Chromosome 12, 114401907: 114401907
45 TBX5 NM_000192.3(TBX5): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic rs104894379 GRCh37 Chromosome 12, 114836480: 114836480
46 TBX5 NM_000192.3(TBX5): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic rs104894379 GRCh38 Chromosome 12, 114398675: 114398675
47 TGFB2 NM_001135599.3(TGFB2): c.294_308delCTACGCCAAGGAGGT (p.Ala100_Tyr104del) deletion Conflicting interpretations of pathogenicity rs398122883 GRCh37 Chromosome 1, 218520337: 218520351
48 TGFB2 NM_001135599.3(TGFB2): c.294_308delCTACGCCAAGGAGGT (p.Ala100_Tyr104del) deletion Conflicting interpretations of pathogenicity rs398122883 GRCh38 Chromosome 1, 218346995: 218347009
49 TGFB2 NM_003238.4(TGFB2): c.643+7A> C single nucleotide variant Benign rs7531245 GRCh37 Chromosome 1, 218607563: 218607563
50 TGFB2 NM_003238.4(TGFB2): c.643+7A> C single nucleotide variant Benign rs7531245 GRCh38 Chromosome 1, 218434221: 218434221

Expression for Holt-Oram Syndrome

Search GEO for disease gene expression data for Holt-Oram Syndrome.

Pathways for Holt-Oram Syndrome

Pathways related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.59 EP300 GATA4 NKX2-5 TGFB2
2
Show member pathways
12.53 GATA4 KAT2B MYH6 NKX2-5 TBX5
3
Show member pathways
12.1 GATA4 MYH7 NKX2-5 TBX5 TGFB2
4
Show member pathways
11.96 MYH6 MYH7 TGFB2
5
Show member pathways
11.81 EP300 GATA4 KAT2B NKX2-5 TBX5
6 11.79 GATA4 NKX2-5 TBX5
7 11.78 EP300 KAT2B TGFB2
8 11.73 EP300 GATA4 KAT2B MYH6
9 11.54 EP300 KAT2B NKX2-5
10 11.42 EP300 KAT2B TGFB2
11 11.14 EP300 KAT2B
12 11.14 EP300 GATA4 NKX2-5 TGFB2
13 10.98 GATA4 MYH6 NKX2-5 TBX5
14 10.84 GATA4 MYH7 NKX2-5
15 10.59 GATA4 NKX2-5 TBX1 TBX5
16 10.21 GATA4 NKX2-5

GO Terms for Holt-Oram Syndrome

Cellular components related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein-containing complex GO:0032991 9.35 EP300 KAT2B NKX2-5 SALL4 TBX5
2 myosin filament GO:0032982 9.26 MYH6 MYH7
3 muscle myosin complex GO:0005859 9.16 MYH6 MYH7
4 protein-DNA complex GO:0032993 8.8 EP300 NKX2-5 TBX5

Biological processes related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

(show all 48)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.99 NKX2-5 TBX1 TBX3 TGFB2
2 in utero embryonic development GO:0001701 9.87 MYH6 SALL4 TBX3
3 positive regulation of transcription, DNA-templated GO:0045893 9.87 EP300 GATA4 KAT2B NKX2-5 TBX1 TBX3
4 heart looping GO:0001947 9.78 GATA4 NKX2-5 TBX3
5 embryonic limb morphogenesis GO:0030326 9.75 SALL4 TBX5 TGFB2
6 outflow tract morphogenesis GO:0003151 9.74 NKX2-5 TBX1 TBX3
7 positive regulation of Notch signaling pathway GO:0045747 9.73 EP300 KAT2B TGFB2
8 cardiac muscle contraction GO:0060048 9.72 MYH6 MYH7 NKX2-5
9 ATP metabolic process GO:0046034 9.7 MYH6 MYH7
10 muscle filament sliding GO:0030049 9.7 MYH6 MYH7
11 regulation of heart rate GO:0002027 9.7 MYH6 MYH7
12 embryonic forelimb morphogenesis GO:0035115 9.7 TBX3 TBX5
13 positive regulation of gene expression, epigenetic GO:0045815 9.69 EP300 KAT2B
14 ventricular septum morphogenesis GO:0060412 9.69 NKX2-5 TBX3 TGFB2
15 thyroid gland development GO:0030878 9.68 NKX2-5 TBX1
16 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.68 MYH6 MYH7
17 embryonic heart tube development GO:0035050 9.68 NKX2-5 TBX3
18 regulation of the force of heart contraction GO:0002026 9.67 MYH6 MYH7
19 pharyngeal system development GO:0060037 9.67 NKX2-5 TBX1
20 positive regulation of transcription of Notch receptor target GO:0007221 9.67 EP300 KAT2B
21 ventricular septum development GO:0003281 9.67 GATA4 SALL4 TBX5
22 heart morphogenesis GO:0003007 9.67 NKX2-5 TBX1 TBX3 TGFB2
23 striated muscle contraction GO:0006941 9.66 MYH6 MYH7
24 ventricular trabecula myocardium morphogenesis GO:0003222 9.66 NKX2-5 TGFB2
25 cardiac muscle hypertrophy in response to stress GO:0014898 9.65 MYH6 MYH7
26 animal organ morphogenesis GO:0009887 9.65 EP300 TBX3
27 cardiac muscle cell proliferation GO:0060038 9.65 NKX2-5 TGFB2
28 outflow tract septum morphogenesis GO:0003148 9.65 NKX2-5 TBX1 TGFB2
29 cardiac right ventricle morphogenesis GO:0003215 9.64 GATA4 TGFB2
30 protein acetylation GO:0006473 9.64 EP300 KAT2B
31 endocardial cushion development GO:0003197 9.63 GATA4 TBX5
32 atrioventricular valve morphogenesis GO:0003181 9.63 TBX5 TGFB2
33 forelimb morphogenesis GO:0035136 9.62 TBX3 TBX5
34 cardiac ventricle morphogenesis GO:0003208 9.62 GATA4 NKX2-5
35 positive regulation of heart contraction GO:0045823 9.61 NKX2-5 TGFB2
36 atrial septum primum morphogenesis GO:0003289 9.6 GATA4 TGFB2
37 internal peptidyl-lysine acetylation GO:0018393 9.59 EP300 KAT2B
38 peptidyl-lysine acetylation GO:0018394 9.58 EP300 KAT2B
39 adult heart development GO:0007512 9.58 MYH6 MYH7 NKX2-5
40 cardiac muscle cell differentiation GO:0055007 9.56 GATA4 NKX2-5 TBX3 TBX5
41 bundle of His development GO:0003166 9.54 NKX2-5 TBX5
42 N-terminal peptidyl-lysine acetylation GO:0018076 9.52 EP300 KAT2B
43 atrial septum morphogenesis GO:0060413 9.46 GATA4 NKX2-5 TBX5 TGFB2
44 tissue development GO:0009888 9.38 SALL4
45 positive regulation of cardioblast differentiation GO:0051891 9.26 GATA4 NKX2-5 TBX5 TGFB2
46 heart development GO:0007507 9.17 EP300 KAT2B NKX2-5 SALL4 TBX1 TBX5
47 regulation of transcription, DNA-templated GO:0006355 10.03 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX1
48 positive regulation of transcription by RNA polymerase II GO:0045944 10 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX1

Molecular functions related to Holt-Oram Syndrome according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.95 GATA4 NKX2-5 SALL4 TBX1 TBX3 TBX5
2 DNA-binding transcription factor activity GO:0003700 9.89 GATA4 NKX2-5 TBX1 TBX3 TBX5
3 sequence-specific DNA binding GO:0043565 9.8 GATA4 NKX2-5 TBX1 TBX3 TBX5
4 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.55 EP300 GATA4 NKX2-5 TBX3 TBX5
5 activating transcription factor binding GO:0033613 9.54 EP300 GATA4
6 acetyltransferase activity GO:0016407 9.52 EP300 KAT2B
7 microfilament motor activity GO:0000146 9.51 MYH6 MYH7
8 RNA polymerase II transcription factor binding GO:0001085 9.5 EP300 GATA4 TBX3
9 actin-dependent ATPase activity GO:0030898 9.43 MYH6 MYH7
10 lysine N-acetyltransferase activity, acting on acetyl phosphate as donor GO:0004468 9.37 EP300 KAT2B
11 peptide-lysine-N-acetyltransferase activity GO:0061733 9.26 EP300 KAT2B
12 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.26 EP300 GATA4 NKX2-5 TBX5
13 transcription factor binding GO:0008134 9.1 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX5
14 DNA binding GO:0003677 10 EP300 GATA4 NKX2-5 SALL4 TBX1 TBX3

Sources for Holt-Oram Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....