Aliases & Classifications for Holt-Oram Syndrome

MalaCards integrated aliases for Holt-Oram Syndrome:

Name: Holt-Oram Syndrome 57 12 24 53 25 75 37 29 13 55 6 44 15 40 73
Atriodigital Dysplasia 57 12 53 25
Hos 57 53 25 75
Heart-Hand Syndrome 57 12 53
Heart-Hand Syndrome, Type 1 53 25
Ventriculo-Radial Syndrome 53 25
Atrio-Digital Syndrome 12 25
Cardiac-Limb Syndrome 53 25
Atrio Digital Syndrome 53
Hearthand Syndrome 24
Holt Oram Syndrome 55
Hos 1 53
Hos1 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
holt-oram syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance The upper-limb malformations in hos are fully penetrant...

Classifications:



Summaries for Holt-Oram Syndrome

NIH Rare Diseases : 53 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 atriodigital dysplasia, is related to duane-radial ray syndrome and atrial heart septal defect. An important gene associated with Holt-Oram Syndrome is TBX5 (T-Box 5), and among its related pathways/superpathways are Cardiac conduction and Human Embryonic Stem Cell Pluripotency. The drugs Doxorubicin and Doxil have been mentioned in the context of this disorder. Affiliated tissues include heart, upper limb and heart, and related phenotypes are pectus excavatum and short clavicles

OMIM : 57 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 : 75 Holt-Oram syndrome: Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects.

Genetics Home Reference : 25 Holt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems.

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

Wikipedia : 76 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 65)
# Related Disease Score Top Affiliating Genes
1 duane-radial ray syndrome 32.7 SALL4 TBX5
2 atrial heart septal defect 30.8 MYH6 NKX2-5 TBX5
3 ventricular septal defect 30.4 MYH7 NKX2-5 TBX5
4 left ventricular noncompaction 29.9 MYH6 MYH7 NKX2-5
5 tetralogy of fallot 29.6 NKX2-5 TBX1 TBX5
6 dilated cardiomyopathy 28.5 MYH6 MYH7 NKX2-5 TBX5 TGFB2
7 heart disease 28.4 MYH6 MYH7 NKX2-5 TBX1 TBX5
8 heart-hand syndrome, slovenian type 12.5
9 heart-hand syndrome, spanish type 12.4
10 tabatznik syndrome 11.5
11 polydactyly, preaxial ii 11.3
12 long-thumb brachydactyly syndrome 10.8
13 murcs association 10.6 TBX3 TBX5
14 heart, malformation of 10.6 MYH6 TBX5
15 acheiropody 10.6 TBX3 TBX5
16 ovarian endodermal sinus tumor 10.4 NKX2-5 SALL4
17 polydactyly 10.4
18 atrial fibrillation 10.4
19 central polydactyly 10.3
20 mayer-rokitansky-kuster-hauser syndrome 10.3 TBX3 TBX5
21 atrial septal defect 4 10.3 MYH6 NKX2-5 TBX5
22 patent foramen ovale 10.3 MYH6 NKX2-5 TBX5
23 ovarian primitive germ cell tumor 10.3 NKX2-5 SALL4
24 myopathy, distal, 1 10.3 MYH6 MYH7
25 myosin storage myopathy 10.3 MYH6 MYH7
26 hypoplastic left heart syndrome 1 10.2
27 hypoplastic left heart syndrome 10.2
28 fetal thalidomide syndrome 10.2
29 ebstein anomaly 10.2 MYH7 NKX2-5
30 tricuspid valve disease 10.2 MYH7 NKX2-5
31 scapuloperoneal myopathy 10.1 MYH6 MYH7
32 kleine-levin hibernation syndrome 10.1
33 monilethrix 10.1
34 pheochromocytoma 10.1
35 prostate cancer 10.1
36 duodenal atresia 10.1
37 lung agenesis 10.1
38 lung agenesis, congenital heart defects, and thumb anomalies syndrome 10.1
39 patent ductus arteriosus 1 10.1
40 pulmonary hypertension 10.1
41 osteonecrosis 10.1
42 microcephaly 10.1
43 myopia 10.1
44 prostatitis 10.1
45 cerebritis 10.1
46 double outlet right ventricle 10.1
47 malignant hyperthermia 10.1
48 duodenitis 10.1
49 lymphosarcoma 10.1
50 aortic coarctation 10.1

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



Diseases related to Holt-Oram Syndrome

Symptoms & Phenotypes for Holt-Oram Syndrome

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Holt-Oram Syndrome:

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

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

26
# 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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.22 EP300 MYH6 MYH7 NKX2-5 SALL4 SHOX2
2 growth/size/body region MP:0005378 10.02 EP300 KAT2B NKX2-5 SALL4 SHOX2 TBX1
3 embryo MP:0005380 10.01 TBX3 TBX5 TGFB2 EP300 KAT2B NKX2-5
4 craniofacial MP:0005382 10 EP300 NKX2-5 SALL4 SHOX2 TBX1 TBX3
5 digestive/alimentary MP:0005381 9.98 EP300 NKX2-5 SALL4 SHOX2 TBX1 TBX3
6 homeostasis/metabolism MP:0005376 9.97 SALL4 SHOX2 TBX1 TBX3 TBX5 TGFB2
7 mortality/aging MP:0010768 9.9 EP300 KAT2B MYH6 NKX2-5 SALL4 SHOX2
8 limbs/digits/tail MP:0005371 9.73 SALL4 SHOX2 TBX1 TBX3 TBX5 TGFB2
9 muscle MP:0005369 9.61 SRSF2 TBX1 TBX3 TBX5 TGFB2 EP300
10 normal MP:0002873 9.1 EP300 KAT2B NKX2-5 TBX1 TBX3 TBX5

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 Antibiotics, Antitubercular Phase 2
5 Topoisomerase Inhibitors 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 29 TBX5

Anatomical Context for Holt-Oram Syndrome

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

19
Heart, Upper Limb

MalaCards organs/tissues related to Holt-Oram Syndrome:

41
Heart, Bone, Testes, Lung, Prostate

Publications for Holt-Oram Syndrome

Articles related to Holt-Oram Syndrome:

(show top 50) (show all 208)
# Title Authors Year
1
Holt-Oram syndrome in two families diagnosed with left ventricular noncompaction and conduction disease. ( 29755943 )
2018
2
Genetic Analyses Identified a SALL4 Gene Mutation Associated with Holt-Oram Syndrome. ( 29461882 )
2018
3
Holt-Oram Syndrome: A Rare Variant. ( 28761211 )
2017
4
KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. ( 28164238 )
2017
5
Holt-Oram syndrome: Anesthetic challenges and safe outcome. ( 28074809 )
2017
6
TBX5 loss-of-function mutation contributes to atrial fibrillation and atypical Holt-Oram syndrome. ( 27035640 )
2016
7
A novel mutated sequence in the T-box transcription factor-5 (TBX-5) gene (c.241A>T) in Holt-Oram syndrome. ( 27026770 )
2016
8
Coexisting urogenital anomaly and duodenal atresia in two atypical Holt-Oram syndrome. ( 27695215 )
2016
9
A "Sleeping Beauty" With a "Heart-Hand": Kleine-Levin Syndrome Treated With Buproprion and Carbamazepine in a Patient With Holt-Oram Syndrome. ( 27090505 )
2016
10
A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome leading to a dramatically reduced biological function. ( 27652283 )
2016
11
Holt-Oram syndrome because of the novel TBX5 mutation c.481A>C. ( 27552067 )
2016
12
Holt-Oram Syndrome Associated with Aortic Atresia: A Rare Association. ( 27293527 )
2016
13
Is there a link between Holt-Oram Syndrome and 'Mardini-Nyhan' association? - need for further research. ( 26990964 )
2016
14
Left Ventricular Non-compaction in Holt-Oram Syndrome. ( 26874791 )
2016
15
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
16
Holt Oram syndrome: a case report and review of the literature. ( 27048037 )
2016
17
Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis. ( 27958623 )
2016
18
Discovering miRNA Regulatory Networks in Holt-Oram Syndrome Using a Zebrafish Model. ( 27471727 )
2016
19
Syndromic anorectal malformation associated with Holt-Oram syndrome, microcephaly, and bilateral corneal opacity: a case report. ( 27495810 )
2016
20
Tetralogy of Fallot with Holt-Oram syndrome: case report and review. ( 25903110 )
2015
21
A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome. ( 26780237 )
2015
22
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
23
Horseshoe Lung Associated With Holt-Oram Syndrome. ( 26195995 )
2015
24
A novel missense mutation in the TBX5 gene in a Saudi infant with Holt-Oram syndrome. ( 26219450 )
2015
25
Defining Features of the Upper Extremity in Holt-Oram Syndrome. ( 26243320 )
2015
26
Monilethrix with holt-oram syndrome: case report of a rare association. ( 25878448 )
2015
27
MicroRNA 19a replacement partially rescues fin and cardiac defects in zebrafish model of Holt Oram syndrome. ( 26657204 )
2015
28
Holt-oram syndrome in adult presenting with heart failure: a rare presentation. ( 24826304 )
2014
29
Holt-Oram syndrome with intermediate atrioventricular canal defect, and aortic coarctation: functional characterization of a de novo TBX5 mutation. ( 24664498 )
2014
30
Novel TBX5 Duplication in a Japanese Family with Holt-Oram Syndrome. ( 25274398 )
2014
31
Holt Oram syndrome: a registry-based study in Europe. ( 25344219 )
2014
32
Anesthetic management of a patient with Holt-Oram syndrome undergoing right radial head excision. ( 25886110 )
2014
33
Holt-Oram syndrome. ( 24656395 )
2014
34
Diversity of congenital cardiac defects and skeletal deformities associated with the Holt-Oram syndrome. ( 24879328 )
2014
35
A New Mutation in the TBX5 Gene in Holt-Oram Syndrome: Two Cases in the Same Family and Prenatal Diagnosis. ( 24408148 )
2014
36
Clinical and molecular characterisation of Holt-Oram syndrome focusing on cardiac manifestations. ( 25216260 )
2014
37
Holt-Oram syndrome: a case report. ( 25455949 )
2014
38
Malignant Hyperthermia-Like Manifestations in a Two-Month-Old Child with Holt-Oram Syndrome Undergoing Cardiac Surgery. ( 24011877 )
2013
39
Prostate Cancer in a Male with Holt-Oram Syndrome: First Clinical Association of the TBX5 Mutation. ( 23984174 )
2013
40
Unexplained right atrial enlargement may be a sign of Holt-Oram syndrome in the fetus. ( 24185902 )
2013
41
Anesthetic implications in Holt-Oram Syndrome. ( 23545878 )
2013
42
Holt-Oram syndrome with aortopulmonary window - a rare association. ( 24124729 )
2013
43
Holt-oram syndrome associated with double outlet right ventricle: A rare association. ( 23626447 )
2013
44
Unusual combination of holt-oram syndrome and persistent left superior vena cava. ( 22129221 )
2012
45
Tetralogy of Fallot with Holt-Oram syndrome. ( 22572437 )
2012
46
TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype. ( 22333898 )
2012
47
Rare cardiac defect in Holt-Oram syndrome. ( 22447508 )
2012
48
Holt-Oram syndrome: novel TBX5 mutation and associated anomalous right coronary artery. ( 21272410 )
2011
49
[Holt-Oram syndrome: family affected without TBX5 mutation and without phenotype manifestations in a probable mutation carrier]. ( 21752519 )
2011
50
A Boy with Holt-Oram Syndrome Caused by Novel Mutation c.1304delT in the TBX5 Gene. ( 22190901 )
2011

Variations for Holt-Oram Syndrome

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

75
# 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 241)
# Gene Variation Type Significance SNP ID Assembly Location
1 TBX5 TBX5, 1491C-T single nucleotide variant Pathogenic
2 TBX5 NM_000192.3(TBX5): c.205G> T (p.Glu69Ter) single nucleotide variant Pathogenic rs104894377 GRCh37 Chromosome 12, 114839668: 114839668
3 TBX5 NM_000192.3(TBX5): c.205G> T (p.Glu69Ter) single nucleotide variant Pathogenic rs104894377 GRCh38 Chromosome 12, 114401863: 114401863
4 TBX5 NM_000192.3(TBX5): c.710G> A (p.Arg237Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894378 GRCh37 Chromosome 12, 114823326: 114823326
5 TBX5 NM_000192.3(TBX5): c.710G> A (p.Arg237Gln) single nucleotide variant Pathogenic/Likely pathogenic rs104894378 GRCh38 Chromosome 12, 114385521: 114385521
6 TBX5 NM_000192.3(TBX5): c.238G> A (p.Gly80Arg) single nucleotide variant Pathogenic rs104894381 GRCh37 Chromosome 12, 114839635: 114839635
7 TBX5 NM_000192.3(TBX5): c.238G> A (p.Gly80Arg) single nucleotide variant Pathogenic rs104894381 GRCh38 Chromosome 12, 114401830: 114401830
8 TBX5 NM_000192.3(TBX5): c.709C> T (p.Arg237Trp) single nucleotide variant Pathogenic rs104894382 GRCh37 Chromosome 12, 114823327: 114823327
9 TBX5 NM_000192.3(TBX5): c.709C> T (p.Arg237Trp) single nucleotide variant Pathogenic rs104894382 GRCh38 Chromosome 12, 114385522: 114385522
10 TBX5 TBX5, 1-BP DEL, 416C deletion Pathogenic
11 TBX5 NM_000192.3(TBX5): c.145C> A (p.Gln49Lys) single nucleotide variant Pathogenic rs104894383 GRCh37 Chromosome 12, 114841559: 114841559
12 TBX5 NM_000192.3(TBX5): c.145C> A (p.Gln49Lys) single nucleotide variant Pathogenic rs104894383 GRCh38 Chromosome 12, 114403754: 114403754
13 TBX5 NM_000192.3(TBX5): c.161T> C (p.Ile54Thr) single nucleotide variant Pathogenic rs104894384 GRCh37 Chromosome 12, 114839712: 114839712
14 TBX5 NM_000192.3(TBX5): c.161T> C (p.Ile54Thr) single nucleotide variant Pathogenic rs104894384 GRCh38 Chromosome 12, 114401907: 114401907
15 TBX5 NM_000192.3(TBX5): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic rs104894379 GRCh37 Chromosome 12, 114836480: 114836480
16 TBX5 NM_000192.3(TBX5): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic rs104894379 GRCh38 Chromosome 12, 114398675: 114398675
17 TGFB2 NM_001135599.2(TGFB2): c.703G> C (p.Val235Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs10482810 GRCh37 Chromosome 1, 218607532: 218607532
18 TGFB2 NM_001135599.2(TGFB2): c.703G> C (p.Val235Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs10482810 GRCh38 Chromosome 1, 218434190: 218434190
19 TBX5 NM_000192.3(TBX5): c.114C> T (p.Ser38=) single nucleotide variant Benign/Likely benign rs34014008 GRCh37 Chromosome 12, 114841590: 114841590
20 TBX5 NM_000192.3(TBX5): c.114C> T (p.Ser38=) single nucleotide variant Benign/Likely benign rs34014008 GRCh38 Chromosome 12, 114403785: 114403785
21 TGFB2 NM_003238.4(TGFB2): c.644-4C> T single nucleotide variant Conflicting interpretations of pathogenicity rs11466408 GRCh37 Chromosome 1, 218607676: 218607676
22 TGFB2 NM_003238.4(TGFB2): c.644-4C> T single nucleotide variant Conflicting interpretations of pathogenicity rs11466408 GRCh38 Chromosome 1, 218434334: 218434334
23 TBX5 NM_000192.3(TBX5): c.787G> A (p.Val263Met) single nucleotide variant Conflicting interpretations of pathogenicity rs147405081 GRCh37 Chromosome 12, 114804165: 114804165
24 TBX5 NM_000192.3(TBX5): c.787G> A (p.Val263Met) single nucleotide variant Conflicting interpretations of pathogenicity rs147405081 GRCh38 Chromosome 12, 114366360: 114366360
25 TGFB2 NM_003238.3(TGFB2): c.114G> A (p.Glu38=) single nucleotide variant Benign/Likely benign rs149215818 GRCh38 Chromosome 1, 218346815: 218346815
26 TGFB2 NM_003238.3(TGFB2): c.114G> A (p.Glu38=) single nucleotide variant Benign/Likely benign rs149215818 GRCh37 Chromosome 1, 218520157: 218520157
27 TGFB2 NM_003238.4(TGFB2): c.236A> G (p.Gln79Arg) single nucleotide variant Uncertain significance rs371241859 GRCh37 Chromosome 1, 218520279: 218520279
28 TGFB2 NM_003238.4(TGFB2): c.236A> G (p.Gln79Arg) single nucleotide variant Uncertain significance rs371241859 GRCh38 Chromosome 1, 218346937: 218346937
29 TGFB2 NM_003238.3(TGFB2): c.272G> A (p.Arg91His) single nucleotide variant Conflicting interpretations of pathogenicity rs10482721 GRCh37 Chromosome 1, 218520315: 218520315
30 TGFB2 NM_003238.3(TGFB2): c.272G> A (p.Arg91His) single nucleotide variant Conflicting interpretations of pathogenicity rs10482721 GRCh38 Chromosome 1, 218346973: 218346973
31 TGFB2 NM_003238.3(TGFB2): c.356C> T (p.Pro119Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh37 Chromosome 1, 218578520: 218578520
32 TGFB2 NM_003238.3(TGFB2): c.356C> T (p.Pro119Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh38 Chromosome 1, 218405178: 218405178
33 TGFB2 NM_003238.3(TGFB2): c.357G> A (p.Pro119=) single nucleotide variant Benign/Likely benign rs138514914 GRCh37 Chromosome 1, 218578521: 218578521
34 TGFB2 NM_003238.3(TGFB2): c.357G> A (p.Pro119=) single nucleotide variant Benign/Likely benign rs138514914 GRCh38 Chromosome 1, 218405179: 218405179
35 TGFB2 NM_003238.4(TGFB2): c.583G> T (p.Glu195Ter) single nucleotide variant Pathogenic rs863223790 GRCh37 Chromosome 1, 218607496: 218607496
36 TGFB2 NM_003238.4(TGFB2): c.583G> T (p.Glu195Ter) single nucleotide variant Pathogenic rs863223790 GRCh38 Chromosome 1, 218434154: 218434154
37 TGFB2 NM_003238.4(TGFB2): c.823A> G (p.Ser275Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs139825195 GRCh37 Chromosome 1, 218609380: 218609380
38 TGFB2 NM_003238.4(TGFB2): c.823A> G (p.Ser275Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs139825195 GRCh38 Chromosome 1, 218436038: 218436038
39 TGFB2 NM_003238.4(TGFB2): c.1239C> T (p.Cys413=) single nucleotide variant Benign/Likely benign rs141225367 GRCh38 Chromosome 1, 218441356: 218441356
40 TGFB2 NM_003238.4(TGFB2): c.1239C> T (p.Cys413=) single nucleotide variant Benign/Likely benign rs141225367 GRCh37 Chromosome 1, 218614698: 218614698
41 TBX5 NM_000192.3(TBX5): c.331G> T (p.Asp111Tyr) single nucleotide variant Benign/Likely benign rs77357563 GRCh37 Chromosome 12, 114837349: 114837349
42 TBX5 NM_000192.3(TBX5): c.331G> T (p.Asp111Tyr) single nucleotide variant Benign/Likely benign rs77357563 GRCh38 Chromosome 12, 114399544: 114399544
43 TBX5 NM_000192.3(TBX5): c.316A> G (p.Ile106Val) single nucleotide variant Likely benign rs147710408 GRCh38 Chromosome 12, 114399559: 114399559
44 TBX5 NM_000192.3(TBX5): c.316A> G (p.Ile106Val) single nucleotide variant Likely benign rs147710408 GRCh37 Chromosome 12, 114837364: 114837364
45 TBX5 NM_000192.3(TBX5): c.309C> T (p.Leu103=) single nucleotide variant Benign rs28730763 GRCh38 Chromosome 12, 114399566: 114399566
46 TBX5 NM_000192.3(TBX5): c.309C> T (p.Leu103=) single nucleotide variant Benign rs28730763 GRCh37 Chromosome 12, 114837371: 114837371
47 TGFB2 NM_001135599.3(TGFB2): c.475C> T (p.Arg159Ter) single nucleotide variant Pathogenic/Likely pathogenic rs869025531 GRCh38 Chromosome 1, 218405213: 218405213
48 TGFB2 NM_001135599.3(TGFB2): c.475C> T (p.Arg159Ter) single nucleotide variant Pathogenic/Likely pathogenic rs869025531 GRCh37 Chromosome 1, 218578555: 218578555
49 TGFB2 NM_003238.4(TGFB2): c.904C> A (p.Arg302Ser) single nucleotide variant Uncertain significance rs869312903 GRCh38 Chromosome 1, 218436119: 218436119
50 TGFB2 NM_003238.4(TGFB2): c.904C> A (p.Arg302Ser) single nucleotide variant Uncertain significance rs869312903 GRCh37 Chromosome 1, 218609461: 218609461

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 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.51 KAT2B MYH6 NKX2-5 TBX5
2
Show member pathways
12.07 MYH7 NKX2-5 TBX5 TGFB2
3
Show member pathways
11.85 MYH6 MYH7 TGFB2
4 11.72 EP300 KAT2B TGFB2
5 11.61 EP300 KAT2B MYH6
6 11.32 EP300 KAT2B NKX2-5
7
Show member pathways
11.18 EP300 KAT2B NKX2-5 TBX5
8 11.07 EP300 KAT2B
9 11.06 MYH6 NKX2-5 TBX5
10 10.79 NKX2-5 TBX1 TBX5
11 10.75 MYH7 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 9.56 KAT2B NKX2-5 SALL4 TBX5
2 muscle myosin complex GO:0005859 9.16 MYH6 MYH7
3 myosin filament GO:0032982 8.96 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 45)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.99 NKX2-5 TBX1 TBX3 TGFB2
2 positive regulation of transcription by RNA polymerase II GO:0045944 9.98 EP300 KAT2B NKX2-5 SALL4 SHOX2 TBX1
3 positive regulation of transcription, DNA-templated GO:0045893 9.88 EP300 KAT2B NKX2-5 TBX1 TBX3 TBX5
4 in utero embryonic development GO:0001701 9.87 MYH6 SALL4 TBX3
5 skeletal system development GO:0001501 9.84 SHOX2 TBX3 TGFB2
6 BMP signaling pathway GO:0030509 9.79 MYH6 NKX2-5 TGFB2
7 outflow tract morphogenesis GO:0003151 9.74 NKX2-5 TBX1 TBX3
8 positive regulation of Notch signaling pathway GO:0045747 9.73 EP300 KAT2B TGFB2
9 cardiac muscle contraction GO:0060048 9.72 MYH6 MYH7 NKX2-5
10 muscle filament sliding GO:0030049 9.7 MYH6 MYH7
11 regulation of heart rate GO:0002027 9.69 MYH6 MYH7
12 ventricular septum development GO:0003281 9.69 SALL4 TBX5
13 ventricular septum morphogenesis GO:0060412 9.69 NKX2-5 TBX3 TGFB2
14 positive regulation of mesenchymal cell proliferation GO:0002053 9.68 SHOX2 TBX1
15 striated muscle contraction GO:0006941 9.68 MYH6 MYH7
16 thyroid gland development GO:0030878 9.68 NKX2-5 TBX1
17 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.67 MYH6 MYH7
18 embryonic heart tube development GO:0035050 9.67 NKX2-5 TBX3
19 embryonic forelimb morphogenesis GO:0035115 9.67 SHOX2 TBX3 TBX5
20 regulation of the force of heart contraction GO:0002026 9.66 MYH6 MYH7
21 pharyngeal system development GO:0060037 9.66 NKX2-5 TBX1
22 positive regulation of transcription of Notch receptor target GO:0007221 9.65 EP300 KAT2B
23 ventricular trabecula myocardium morphogenesis GO:0003222 9.65 NKX2-5 TGFB2
24 cardiac muscle cell proliferation GO:0060038 9.65 NKX2-5 TGFB2
25 cardiac muscle cell differentiation GO:0055007 9.65 NKX2-5 TBX3 TBX5
26 cardiac muscle hypertrophy in response to stress GO:0014898 9.64 MYH6 MYH7
27 protein acetylation GO:0006473 9.64 EP300 KAT2B
28 forelimb morphogenesis GO:0035136 9.63 TBX3 TBX5
29 outflow tract septum morphogenesis GO:0003148 9.63 NKX2-5 TBX1 TGFB2
30 atrioventricular valve morphogenesis GO:0003181 9.62 TBX5 TGFB2
31 positive regulation of heart contraction GO:0045823 9.61 NKX2-5 TGFB2
32 muscle tissue morphogenesis GO:0060415 9.59 SHOX2 TBX1
33 peptidyl-lysine acetylation GO:0018394 9.58 EP300 KAT2B
34 internal peptidyl-lysine acetylation GO:0018393 9.58 EP300 KAT2B
35 embryonic limb morphogenesis GO:0030326 9.56 SALL4 SHOX2 TBX5 TGFB2
36 N-terminal peptidyl-lysine acetylation GO:0018076 9.54 EP300 KAT2B
37 adult heart development GO:0007512 9.54 MYH6 MYH7 NKX2-5
38 bundle of His development GO:0003166 9.52 NKX2-5 TBX5
39 atrial septum morphogenesis GO:0060413 9.5 NKX2-5 TBX5 TGFB2
40 heart morphogenesis GO:0003007 9.46 NKX2-5 TBX1 TBX3 TGFB2
41 heart development GO:0007507 9.23 EP300 KAT2B NKX2-5 SALL4 SHOX2 TBX1
42 positive regulation of cardioblast differentiation GO:0051891 9.13 NKX2-5 TBX5 TGFB2
43 regulation of transcription, DNA-templated GO:0006355 10.2 EP300 KAT2B NKX2-5 SALL4 SHOX2 TBX1
44 multicellular organism development GO:0007275 10.09 NKX2-5 SALL4 SHOX2 TBX1 TBX3 TBX5
45 negative regulation of transcription by RNA polymerase II GO:0000122 10.03 EP300 NKX2-5 SALL4 SHOX2 TBX3

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.95 NKX2-5 SALL4 SHOX2 TBX1 TBX3 TBX5
2 DNA binding transcription factor activity GO:0003700 9.91 NKX2-5 SALL4 TBX1 TBX3 TBX5
3 DNA binding GO:0003677 9.91 EP300 NKX2-5 SALL4 SHOX2 TBX1 TBX3
4 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.73 EP300 NKX2-5 TBX3 TBX5
5 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding GO:0001228 9.67 EP300 NKX2-5 TBX5
6 microfilament motor activity GO:0000146 9.46 MYH6 MYH7
7 sequence-specific DNA binding GO:0043565 9.43 NKX2-5 SALL4 SHOX2 TBX1 TBX3 TBX5
8 acetyltransferase activity GO:0016407 9.4 EP300 KAT2B
9 actin-dependent ATPase activity GO:0030898 9.32 MYH6 MYH7
10 lysine N-acetyltransferase activity, acting on acetyl phosphate as donor GO:0004468 9.26 EP300 KAT2B
11 peptide-lysine-N-acetyltransferase activity GO:0061733 9.16 EP300 KAT2B
12 transcription factor binding GO:0008134 9.02 EP300 KAT2B NKX2-5 SALL4 TBX5

Sources for Holt-Oram Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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