HOS
MCID: HLT001
MIFTS: 60

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 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
Holtoram Syndrome 76
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, bone and testes, and related phenotypes are pectus excavatum and finger syndactyly

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

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

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.

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 68)
# Related Disease Score Top Affiliating Genes
1 duane-radial ray syndrome 32.4 TBX5 SALL4
2 atrial heart septal defect 30.5 TBX5 NKX2-5 MYH6
3 ventricular septal defect 30.4 TBX5 NKX2-5 MYH7
4 tetralogy of fallot 30.3 TBX5 TBX1 NKX2-5
5 left ventricular noncompaction 30.3 NKX2-5 MYH7 MYH6
6 heart disease 29.9 TBX5 TBX1 NKX2-5 MYH7 MYH6
7 dilated cardiomyopathy 29.4 TGFB2 TBX5 NKX2-5 MYH7 MYH6
8 heart-hand syndrome, slovenian type 12.6
9 heart-hand syndrome, spanish type 12.5
10 tabatznik syndrome 11.7
11 polydactyly, preaxial ii 11.5
12 long-thumb brachydactyly syndrome 11.0
13 polydactyly 10.5
14 atrial fibrillation 10.5
15 central polydactyly 10.5
16 hypoplastic left heart syndrome 1 10.4
17 hypoplastic left heart syndrome 10.4
18 fetal thalidomide syndrome 10.4
19 kleine-levin hibernation syndrome 10.2
20 monilethrix 10.2
21 pheochromocytoma 10.2
22 prostate cancer 10.2
23 duodenal atresia 10.2
24 lung agenesis 10.2
25 lung agenesis, congenital heart defects, and thumb anomalies syndrome 10.2
26 patent ductus arteriosus 1 10.2
27 pulmonary hypertension 10.2
28 crohn's disease 10.2
29 osteonecrosis 10.2
30 malignant pheochromocytoma 10.2
31 microcephaly 10.2
32 myopia 10.2
33 double outlet right ventricle 10.2
34 malignant hyperthermia 10.2
35 lymphosarcoma 10.2
36 aortic coarctation 10.2
37 aortopulmonary window 10.2
38 syncope 10.2
39 radial hemimelia 10.2
40 double-orifice mitral valve 10.2
41 murcs association 10.2 TBX5 TBX3
42 heart, malformation of 10.2 TBX5 MYH6
43 acheiropody 10.2 TBX5 TBX3
44 horns in sheep 10.2
45 ovarian endodermal sinus tumor 10.1 SALL4 NKX2-5
46 ovarian primitive germ cell tumor 10.1 SALL4 NKX2-5
47 myosin storage myopathy 10.1 MYH7 MYH6
48 patent foramen ovale 10.1 TBX5 NKX2-5 MYH6
49 mayer-rokitansky-kuster-hauser syndrome 10.1 TBX5 TBX3
50 myopathy, distal, 1 10.1 MYH7 MYH6

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

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 EP300 KAT2B NKX2-5 SALL4 TBX1 TBX3
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 EP300 MYH6 NKX2-5 SALL4 SHOX2 TBX1
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 EP300 MYH6 MYH7 NKX2-5 SRSF2 TBX1
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

MalaCards organs/tissues related to Holt-Oram Syndrome:

41
Heart, Bone, Testes, Lung, Prostate

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

19
Heart, Upper Limb

Publications for Holt-Oram Syndrome

Articles related to Holt-Oram Syndrome:

(show top 50) (show all 214)
# Title Authors Year
1
Holt-Oram syndrome in two families diagnosed with left ventricular noncompaction and conduction disease. ( 29755943 )
2018
2
Holt-Oram Syndrome in a Patient with Crohn's Disease: a Rare Case Report and Literature Review. ( 30514998 )
2018
3
An Unusual Finding of a Double Orifice Mitral Valve in a Patient With Holt-Oram Syndrome. ( 30555010 )
2018
4
Genetic Analyses Identified a SALL4 Gene Mutation Associated with Holt-Oram Syndrome. ( 29461882 )
2018
5
Holt-Oram Syndrome With Multiple Cardiac Abnormalities. ( 30344832 )
2018
6
A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome. ( 30538526 )
2018
7
Holt-Oram syndrome: clinical and molecular description of 78 patients with TBX5 variants. ( 30552424 )
2018
8
Holt-Oram Syndrome: A Rare Variant. ( 28761211 )
2017
9
KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. ( 28164238 )
2017
10
Holt-Oram syndrome: Anesthetic challenges and safe outcome. ( 28074809 )
2017
11
TBX5 loss-of-function mutation contributes to atrial fibrillation and atypical Holt-Oram syndrome. ( 27035640 )
2016
12
A novel mutated sequence in the T-box transcription factor-5 (TBX-5) gene (c.241A>T) in Holt-Oram syndrome. ( 27026770 )
2016
13
Coexisting urogenital anomaly and duodenal atresia in two atypical Holt-Oram syndrome. ( 27695215 )
2016
14
A "Sleeping Beauty" With a "Heart-Hand": Kleine-Levin Syndrome Treated With Buproprion and Carbamazepine in a Patient With Holt-Oram Syndrome. ( 27090505 )
2016
15
A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome leading to a dramatically reduced biological function. ( 27652283 )
2016
16
Holt-Oram syndrome because of the novel TBX5 mutation c.481A>C. ( 27552067 )
2016
17
Holt-Oram Syndrome Associated with Aortic Atresia: A Rare Association. ( 27293527 )
2016
18
Is there a link between Holt-Oram Syndrome and 'Mardini-Nyhan' association? - need for further research. ( 26990964 )
2016
19
Left Ventricular Non-compaction in Holt-Oram Syndrome. ( 26874791 )
2016
20
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
21
Holt Oram syndrome: a case report and review of the literature. ( 27048037 )
2016
22
Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis. ( 27958623 )
2016
23
Discovering miRNA Regulatory Networks in Holt-Oram Syndrome Using a Zebrafish Model. ( 27471727 )
2016
24
Syndromic anorectal malformation associated with Holt-Oram syndrome, microcephaly, and bilateral corneal opacity: a case report. ( 27495810 )
2016
25
Tetralogy of Fallot with Holt-Oram syndrome: case report and review. ( 25903110 )
2015
26
A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome. ( 26780237 )
2015
27
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
28
Horseshoe Lung Associated With Holt-Oram Syndrome. ( 26195995 )
2015
29
A novel missense mutation in the TBX5 gene in a Saudi infant with Holt-Oram syndrome. ( 26219450 )
2015
30
Defining Features of the Upper Extremity in Holt-Oram Syndrome. ( 26243320 )
2015
31
Monilethrix with holt-oram syndrome: case report of a rare association. ( 25878448 )
2015
32
MicroRNA 19a replacement partially rescues fin and cardiac defects in zebrafish model of Holt Oram syndrome. ( 26657204 )
2015
33
Holt-oram syndrome in adult presenting with heart failure: a rare presentation. ( 24826304 )
2014
34
Holt-Oram syndrome with intermediate atrioventricular canal defect, and aortic coarctation: functional characterization of a de novo TBX5 mutation. ( 24664498 )
2014
35
Novel TBX5 Duplication in a Japanese Family with Holt-Oram Syndrome. ( 25274398 )
2014
36
Holt Oram syndrome: a registry-based study in Europe. ( 25344219 )
2014
37
Anesthetic management of a patient with Holt-Oram syndrome undergoing right radial head excision. ( 25886110 )
2014
38
Holt-Oram syndrome. ( 24656395 )
2014
39
Diversity of congenital cardiac defects and skeletal deformities associated with the Holt-Oram syndrome. ( 24879328 )
2014
40
A New Mutation in the TBX5 Gene in Holt-Oram Syndrome: Two Cases in the Same Family and Prenatal Diagnosis. ( 24408148 )
2014
41
Clinical and molecular characterisation of Holt-Oram syndrome focusing on cardiac manifestations. ( 25216260 )
2014
42
Holt-Oram syndrome: a case report. ( 25455949 )
2014
43
Malignant Hyperthermia-Like Manifestations in a Two-Month-Old Child with Holt-Oram Syndrome Undergoing Cardiac Surgery. ( 24011877 )
2013
44
Prostate Cancer in a Male with Holt-Oram Syndrome: First Clinical Association of the TBX5 Mutation. ( 23984174 )
2013
45
Unexplained right atrial enlargement may be a sign of Holt-Oram syndrome in the fetus. ( 24185902 )
2013
46
Anesthetic implications in Holt-Oram Syndrome. ( 23545878 )
2013
47
Holt-Oram syndrome with aortopulmonary window - a rare association. ( 24124729 )
2013
48
Holt-oram syndrome associated with double outlet right ventricle: A rare association. ( 23626447 )
2013
49
A genetic assay of three patients in the same family with Holt-Oram syndrome; a case report. ( 26989721 )
2013
50
Unusual combination of holt-oram syndrome and persistent left superior vena cava. ( 22129221 )
2012

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 271)
# 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_001135599.3(TGFB2): c.294_308delCTACGCCAAGGAGGT (p.Ala100_Tyr104del) deletion Conflicting interpretations of pathogenicity rs398122883 GRCh37 Chromosome 1, 218520337: 218520351
18 TGFB2 NM_001135599.3(TGFB2): c.294_308delCTACGCCAAGGAGGT (p.Ala100_Tyr104del) deletion Conflicting interpretations of pathogenicity rs398122883 GRCh38 Chromosome 1, 218346995: 218347009
19 TGFB2 NM_003238.4(TGFB2): c.643+7A> C single nucleotide variant Benign rs7531245 GRCh37 Chromosome 1, 218607563: 218607563
20 TGFB2 NM_003238.4(TGFB2): c.643+7A> C single nucleotide variant Benign rs7531245 GRCh38 Chromosome 1, 218434221: 218434221
21 TGFB2 NM_001135599.2(TGFB2): c.703G> C (p.Val235Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs10482810 GRCh37 Chromosome 1, 218607532: 218607532
22 TGFB2 NM_001135599.2(TGFB2): c.703G> C (p.Val235Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs10482810 GRCh38 Chromosome 1, 218434190: 218434190
23 TBX5 NM_000192.3(TBX5): c.114C> T (p.Ser38=) single nucleotide variant Benign/Likely benign rs34014008 GRCh37 Chromosome 12, 114841590: 114841590
24 TBX5 NM_000192.3(TBX5): c.114C> T (p.Ser38=) single nucleotide variant Benign/Likely benign rs34014008 GRCh38 Chromosome 12, 114403785: 114403785
25 TGFB2 NM_003238.4(TGFB2): c.644-4C> T single nucleotide variant Conflicting interpretations of pathogenicity rs11466408 GRCh37 Chromosome 1, 218607676: 218607676
26 TGFB2 NM_003238.4(TGFB2): c.644-4C> T single nucleotide variant Conflicting interpretations of pathogenicity rs11466408 GRCh38 Chromosome 1, 218434334: 218434334
27 TBX5 NM_000192.3(TBX5): c.787G> A (p.Val263Met) single nucleotide variant Conflicting interpretations of pathogenicity rs147405081 GRCh37 Chromosome 12, 114804165: 114804165
28 TBX5 NM_000192.3(TBX5): c.787G> A (p.Val263Met) single nucleotide variant Conflicting interpretations of pathogenicity rs147405081 GRCh38 Chromosome 12, 114366360: 114366360
29 TGFB2 NM_003238.3(TGFB2): c.114G> A (p.Glu38=) single nucleotide variant Benign/Likely benign rs149215818 GRCh38 Chromosome 1, 218346815: 218346815
30 TGFB2 NM_003238.3(TGFB2): c.114G> A (p.Glu38=) single nucleotide variant Benign/Likely benign rs149215818 GRCh37 Chromosome 1, 218520157: 218520157
31 TGFB2 NM_003238.4(TGFB2): c.199G> A (p.Val67Met) single nucleotide variant Uncertain significance rs201761868 GRCh37 Chromosome 1, 218520242: 218520242
32 TGFB2 NM_003238.4(TGFB2): c.199G> A (p.Val67Met) single nucleotide variant Uncertain significance rs201761868 GRCh38 Chromosome 1, 218346900: 218346900
33 TGFB2 NM_003238.4(TGFB2): c.236A> G (p.Gln79Arg) single nucleotide variant Uncertain significance rs371241859 GRCh37 Chromosome 1, 218520279: 218520279
34 TGFB2 NM_003238.4(TGFB2): c.236A> G (p.Gln79Arg) single nucleotide variant Uncertain significance rs371241859 GRCh38 Chromosome 1, 218346937: 218346937
35 TGFB2 NM_003238.3(TGFB2): c.272G> A (p.Arg91His) single nucleotide variant Conflicting interpretations of pathogenicity rs10482721 GRCh37 Chromosome 1, 218520315: 218520315
36 TGFB2 NM_003238.3(TGFB2): c.272G> A (p.Arg91His) single nucleotide variant Conflicting interpretations of pathogenicity rs10482721 GRCh38 Chromosome 1, 218346973: 218346973
37 TGFB2 NM_003238.3(TGFB2): c.356C> T (p.Pro119Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh37 Chromosome 1, 218578520: 218578520
38 TGFB2 NM_003238.3(TGFB2): c.356C> T (p.Pro119Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149533093 GRCh38 Chromosome 1, 218405178: 218405178
39 TGFB2 NM_003238.3(TGFB2): c.357G> A (p.Pro119=) single nucleotide variant Benign/Likely benign rs138514914 GRCh37 Chromosome 1, 218578521: 218578521
40 TGFB2 NM_003238.3(TGFB2): c.357G> A (p.Pro119=) single nucleotide variant Benign/Likely benign rs138514914 GRCh38 Chromosome 1, 218405179: 218405179
41 TGFB2 NM_003238.4(TGFB2): c.583G> T (p.Glu195Ter) single nucleotide variant Pathogenic rs863223790 GRCh37 Chromosome 1, 218607496: 218607496
42 TGFB2 NM_003238.4(TGFB2): c.583G> T (p.Glu195Ter) single nucleotide variant Pathogenic rs863223790 GRCh38 Chromosome 1, 218434154: 218434154
43 TGFB2 NM_003238.4(TGFB2): c.823A> G (p.Ser275Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs139825195 GRCh37 Chromosome 1, 218609380: 218609380
44 TGFB2 NM_003238.4(TGFB2): c.823A> G (p.Ser275Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs139825195 GRCh38 Chromosome 1, 218436038: 218436038
45 TGFB2 NM_003238.4(TGFB2): c.1239C> T (p.Cys413=) single nucleotide variant Benign/Likely benign rs141225367 GRCh38 Chromosome 1, 218441356: 218441356
46 TGFB2 NM_003238.4(TGFB2): c.1239C> T (p.Cys413=) single nucleotide variant Benign/Likely benign rs141225367 GRCh37 Chromosome 1, 218614698: 218614698
47 TBX5 NM_000192.3(TBX5): c.331G> T (p.Asp111Tyr) single nucleotide variant Benign/Likely benign rs77357563 GRCh37 Chromosome 12, 114837349: 114837349
48 TBX5 NM_000192.3(TBX5): c.331G> T (p.Asp111Tyr) single nucleotide variant Benign/Likely benign rs77357563 GRCh38 Chromosome 12, 114399544: 114399544
49 TBX5 NM_000192.3(TBX5): c.316A> G (p.Ile106Val) single nucleotide variant Likely benign rs147710408 GRCh38 Chromosome 12, 114399559: 114399559
50 TBX5 NM_000192.3(TBX5): c.316A> G (p.Ile106Val) single nucleotide variant Likely benign rs147710408 GRCh37 Chromosome 12, 114837364: 114837364

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 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.52 KAT2B MYH6 NKX2-5 TBX5
2
Show member pathways
12.07 MYH7 NKX2-5 TBX5 TGFB2
3
Show member pathways
11.89 MYH6 MYH7 TGFB2
4 11.72 EP300 KAT2B TGFB2
5 11.61 EP300 KAT2B MYH6
6 11.34 EP300 KAT2B TGFB2
7 11.32 EP300 KAT2B NKX2-5
8
Show member pathways
11.18 EP300 KAT2B NKX2-5 TBX5
9 11.12 EP300 KAT2B
10 11.09 EP300 KAT2B
11 11.06 MYH6 NKX2-5 TBX5
12 10.79 NKX2-5 TBX1 TBX5
13 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 9.35 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 45)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.98 NKX2-5 TBX1 TBX3 TGFB2
2 positive regulation of transcription, DNA-templated GO:0045893 9.91 EP300 KAT2B NKX2-5 TBX1 TBX3 TBX5
3 in utero embryonic development GO:0001701 9.86 MYH6 SALL4 TBX3
4 skeletal system development GO:0001501 9.84 SHOX2 TBX3 TGFB2
5 outflow tract morphogenesis GO:0003151 9.74 NKX2-5 TBX1 TBX3
6 positive regulation of Notch signaling pathway GO:0045747 9.73 EP300 KAT2B TGFB2
7 cardiac muscle contraction GO:0060048 9.72 MYH6 MYH7 NKX2-5
8 ATP metabolic process GO:0046034 9.7 MYH6 MYH7
9 muscle filament sliding GO:0030049 9.69 MYH6 MYH7
10 regulation of heart rate GO:0002027 9.69 MYH6 MYH7
11 positive regulation of gene expression, epigenetic GO:0045815 9.69 EP300 KAT2B
12 ventricular septum morphogenesis GO:0060412 9.69 NKX2-5 TBX3 TGFB2
13 ventricular septum development GO:0003281 9.68 SALL4 TBX5
14 positive regulation of mesenchymal cell proliferation GO:0002053 9.67 SHOX2 TBX1
15 thyroid gland development GO:0030878 9.67 NKX2-5 TBX1
16 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.67 MYH6 MYH7
17 embryonic forelimb morphogenesis GO:0035115 9.67 SHOX2 TBX3 TBX5
18 embryonic heart tube development GO:0035050 9.66 NKX2-5 TBX3
19 regulation of the force of heart contraction GO:0002026 9.65 MYH6 MYH7
20 pharyngeal system development GO:0060037 9.65 NKX2-5 TBX1
21 positive regulation of transcription of Notch receptor target GO:0007221 9.65 EP300 KAT2B
22 outflow tract septum morphogenesis GO:0003148 9.65 NKX2-5 TBX1 TGFB2
23 striated muscle contraction GO:0006941 9.64 MYH6 MYH7
24 ventricular trabecula myocardium morphogenesis GO:0003222 9.64 NKX2-5 TGFB2
25 cardiac muscle hypertrophy in response to stress GO:0014898 9.63 MYH6 MYH7
26 cardiac muscle cell proliferation GO:0060038 9.63 NKX2-5 TGFB2
27 cardiac muscle cell differentiation GO:0055007 9.63 NKX2-5 TBX3 TBX5
28 protein acetylation GO:0006473 9.62 EP300 KAT2B
29 atrioventricular valve morphogenesis GO:0003181 9.62 TBX5 TGFB2
30 forelimb morphogenesis GO:0035136 9.61 TBX3 TBX5
31 positive regulation of heart contraction GO:0045823 9.61 NKX2-5 TGFB2
32 muscle tissue morphogenesis GO:0060415 9.59 SHOX2 TBX1
33 internal peptidyl-lysine acetylation GO:0018393 9.58 EP300 KAT2B
34 peptidyl-lysine acetylation GO:0018394 9.58 EP300 KAT2B
35 embryonic limb morphogenesis GO:0030326 9.56 SALL4 SHOX2 TBX5 TGFB2
36 bundle of His development GO:0003166 9.54 NKX2-5 TBX5
37 adult heart development GO:0007512 9.54 MYH6 MYH7 NKX2-5
38 N-terminal peptidyl-lysine acetylation GO:0018076 9.52 EP300 KAT2B
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 multicellular organism development GO:0007275 10.08 NKX2-5 SHOX2 TBX1 TBX3 TBX5
44 positive regulation of transcription by RNA polymerase II GO:0045944 10.08 EP300 KAT2B NKX2-5 SALL4 TBX1 TBX5
45 regulation of transcription, DNA-templated GO:0006355 10.01 EP300 KAT2B NKX2-5 SALL4 SHOX2 TBX1

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.91 EP300 NKX2-5 SALL4 SHOX2 TBX1 TBX3
2 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.88 NKX2-5 SALL4 SHOX2 TBX1 TBX3 TBX5
3 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.78 EP300 NKX2-5 TBX3 TBX5
4 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.67 EP300 NKX2-5 TBX5
5 sequence-specific DNA binding GO:0043565 9.65 NKX2-5 SHOX2 TBX1 TBX3 TBX5
6 acetyltransferase activity GO:0016407 9.46 EP300 KAT2B
7 microfilament motor activity GO:0000146 9.43 MYH6 MYH7
8 actin-dependent ATPase activity GO:0030898 9.32 MYH6 MYH7
9 lysine N-acetyltransferase activity, acting on acetyl phosphate as donor GO:0004468 9.16 EP300 KAT2B
10 transcription factor binding GO:0008134 9.02 EP300 KAT2B NKX2-5 SALL4 TBX5
11 peptide-lysine-N-acetyltransferase activity GO:0061733 8.96 EP300 KAT2B

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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