HOS
MCID: HLT001
MIFTS: 62

Holt-Oram Syndrome (HOS)

Categories: Bone diseases, Cardiovascular diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Holt-Oram Syndrome

MalaCards integrated aliases for Holt-Oram Syndrome:

Name: Holt-Oram Syndrome 57 12 75 24 53 25 59 74 37 29 13 55 6 44 15 40 72
Hos 57 53 25 59 74 17
Atriodigital Dysplasia 57 12 53 25 59
Heart-Hand Syndrome 57 12 53 59
Heart-Hand Syndrome, Type 1 53 25
Ventriculo-Radial Syndrome 53 25
Atrio-Digital Syndrome 12 25
Cardiac-Limb Syndrome 53 25
Atriodigital Dysplasia Type 1 59
Heart-Hand Syndrome Type 1 59
Atrio Digital Syndrome 53
Heart Hand Syndrome 24
Holt Oram Syndrome 55
Hos 1 53
Hos1 57

Characteristics:

Orphanet epidemiological data:

59
holt-oram syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (Hungary); Age of onset: Neonatal; Age of death: any age;

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:



External Ids:

Disease Ontology 12 DOID:0060468
OMIM 57 142900
KEGG 37 H00433
MeSH 44 C535326
NCIt 50 C125592
SNOMED-CT 68 19092004
ICD10 33 Q87.2
MESH via Orphanet 45 C535326
ICD10 via Orphanet 34 Q87.2
UMLS via Orphanet 73 C0265264
MedGen 42 C0265264
UMLS 72 C0265264

Summaries for Holt-Oram Syndrome

Genetics Home Reference : 25 Holt-Oram syndrome is characterized by skeletal abnormalities of the hands and arms (upper limbs) and heart problems. People with Holt-Oram syndrome have abnormally developed bones in their upper limbs. At least one abnormality in the bones of the wrist (carpal bones) is present in affected individuals. Often, these wrist bone abnormalities can be detected only by x-ray. Individuals with Holt-Oram syndrome may have additional bone abnormalities including a missing thumb, a long thumb that looks like a finger, partial or complete absence of bones in the forearm, an underdeveloped bone of the upper arm, and abnormalities of the collar bone or shoulder blades. These skeletal abnormalities may affect one or both of the upper limbs. If both upper limbs are affected, the bone abnormalities can be the same or different on each side. In cases where the skeletal abnormalities are not the same on both sides of the body, the left side is usually more severely affected than the right side. About 75 percent of individuals with Holt-Oram syndrome have heart (cardiac) problems, which can be life-threatening. The most common problem is a defect in the muscular wall (septum) that separates the right and left sides of the heart. A hole in the septum between the upper chambers of the heart (atria) is called an atrial septal defect (ASD), and a hole in the septum between the lower chambers of the heart (ventricles) is called a ventricular septal defect (VSD). Some people with Holt-Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slower-than-normal heart rate (bradycardia) or a rapid and uncoordinated contraction of the heart muscle (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as ASD or VSD) or as the only heart problem in people with Holt-Oram syndrome. The features of Holt-Oram syndrome are similar to those of a condition called Duane-radial ray syndrome; however, these two disorders are caused by mutations in different genes.

MalaCards based summary : Holt-Oram Syndrome, also known as hos, is related to duane-radial ray syndrome and ventricular septal defect. An important gene associated with Holt-Oram Syndrome is TBX5 (T-Box Transcription Factor 5), and among its related pathways/superpathways are NFAT and Cardiac Hypertrophy and Cardiac conduction. Affiliated tissues include heart, upper limb and heart, 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.

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.

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)

KEGG : 37
Holt-Oram syndrome (HOS) is an autosomal-dominant disorder characterized by bilateral forelimb anomalies and congenital heart diseases. All patients with HOS have abnormal carpal bones and about 85% to 95% develop cardiac malformation including atrial septal defect and ventricular septal defect. The disease is caused by mutations of the T-box transcription factor TBX5.

UniProtKB/Swiss-Prot : 74 Holt-Oram syndrome: Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects.

Wikipedia : 75 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 158)
# Related Disease Score Top Affiliating Genes
1 duane-radial ray syndrome 33.6 TBX5 SALL4
2 ventricular septal defect 32.1 TBX5 NKX2-5 MYH7 GATA4
3 atrial heart septal defect 30.9 TBX5 NKX2-5 MYH6 GATA4
4 atrioventricular block 30.6 TBX5 NKX2-5 GATA4
5 heart septal defect 30.5 TBX5 TBX1 NKX2-5 GATA4
6 sinoatrial node disease 30.4 TBX3 MYH6 GJA5
7 left ventricular noncompaction 30.4 NKX2-5 MYH7 MYH6
8 char syndrome 30.1 TBX5 NKX2-5 EP300
9 atrial standstill 1 30.1 MYH7 MYH6 GJA5
10 double outlet right ventricle 29.7 TBX1 NKX2-5 GATA4
11 ulnar-mammary syndrome 29.7 TBX5 TBX3 TBX1
12 atrioventricular septal defect 29.6 TBX5 TBX1 NKX2-5 GATA4
13 patent foramen ovale 29.0 TBX5 NKX2-5 MYH6 GATA4
14 tetralogy of fallot 29.0 TBX5 TBX1 NKX2-5 GJA5 GATA4
15 heart disease 28.1 TBX5 TBX1 NKX2-5 MYH7 MYH6 GJA5
16 dilated cardiomyopathy 27.5 TGFB2 TBX5 NKX2-5 MYH7 MYH6 GJA5
17 heart-hand syndrome, slovenian type 12.9
18 heart-hand syndrome, spanish type 12.8
19 tabatznik syndrome 11.8
20 polydactyly, preaxial ii 11.6
21 long-thumb brachydactyly syndrome 11.1
22 phocomelia 10.8
23 polydactyly 10.6
24 patent ductus arteriosus 1 10.6
25 atrial fibrillation 10.6
26 murcs association 10.5 TBX5 TBX3
27 heart, malformation of 10.5 TBX5 MYH6
28 hypoplastic left heart syndrome 10.5
29 atrial septal defect ostium primum 10.5
30 central polydactyly 10.5
31 acheiropody 10.5 TBX5 TBX3
32 hypertelorism 10.4
33 radioulnar synostosis 10.4
34 renal hypodysplasia/aplasia 1 10.4
35 thrombocytopenia-absent radius syndrome 10.4
36 tricuspid atresia 10.4
37 pulmonary hypertension 10.4
38 scoliosis 10.4
39 synostosis 10.4
40 sick sinus syndrome 10.4
41 sall4-related disorders 10.4
42 congenital radioulnar synostosis 10.4
43 fetal thalidomide syndrome 10.4
44 ovarian endodermal sinus tumor 10.3 SALL4 NKX2-5
45 townes-brocks syndrome 1 10.3
46 aortic valve disease 1 10.3
47 progressive familial heart block, type ia 10.3
48 cardiac arrhythmia 10.3
49 cardiac conduction defect 10.3
50 cleft palate, isolated 10.3

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:

59 32 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001387
2 split hand 59 32 hallmark (90%) Very frequent (99-80%) HP:0001171
3 abnormality of the clavicle 59 32 hallmark (90%) Very frequent (99-80%) HP:0000889
4 scoliosis 59 32 frequent (33%) Frequent (79-30%) HP:0002650
5 kyphosis 59 32 frequent (33%) Frequent (79-30%) HP:0002808
6 atrial septal defect 59 32 frequent (33%) Frequent (79-30%) HP:0001631
7 first degree atrioventricular block 59 32 frequent (33%) Frequent (79-30%) HP:0011705
8 abnormality of the metacarpal bones 59 32 frequent (33%) Frequent (79-30%) HP:0001163
9 ventricular septal defect 59 32 very rare (1%) Frequent (79-30%) HP:0001629
10 triphalangeal thumb 59 32 very rare (1%) Frequent (79-30%) HP:0001199
11 aplasia/hypoplasia of the radius 59 32 frequent (33%) Frequent (79-30%) HP:0006501
12 paroxysmal atrial fibrillation 59 32 frequent (33%) Frequent (79-30%) HP:0004757
13 absent thumb 59 32 very rare (1%) Frequent (79-30%) HP:0009777
14 pectus excavatum 59 32 very rare (1%) Occasional (29-5%) HP:0000767
15 finger syndactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0006101
16 broad thumb 59 32 occasional (7.5%) Occasional (29-5%) HP:0011304
17 patent ductus arteriosus 59 32 very rare (1%) Occasional (29-5%) HP:0001643
18 hypoplastic left heart 59 32 occasional (7.5%) Occasional (29-5%) HP:0004383
19 sprengel anomaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000912
20 abnormality of the ribs 59 32 occasional (7.5%) Occasional (29-5%) HP:0000772
21 radioulnar synostosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002974
22 down-sloping shoulders 59 32 occasional (7.5%) Occasional (29-5%) HP:0200021
23 atrioventricular canal defect 59 32 occasional (7.5%) Occasional (29-5%) HP:0006695
24 abnormal aortic morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0001679
25 phocomelia 59 32 occasional (7.5%) Occasional (29-5%) HP:0009829
26 abnormality of the humerus 59 32 occasional (7.5%) Occasional (29-5%) HP:0003063
27 anomalous pulmonary venous return 59 32 occasional (7.5%) Occasional (29-5%) HP:0010772
28 hypoplasia of the ulna 32 very rare (1%) HP:0003022
29 finger clinodactyly 32 very rare (1%) HP:0040019
30 secundum atrial septal defect 32 very rare (1%) HP:0001684
31 hypoplasia of the radius 32 very rare (1%) HP:0002984
32 short clavicles 32 very rare (1%) HP:0000894
33 aplasia of the pectoralis major muscle 32 very rare (1%) HP:0009751
34 absent radius 32 very rare (1%) HP:0003974
35 limited elbow extension 32 very rare (1%) HP:0001377
36 syndactyly 32 very rare (1%) HP:0001159
37 short humerus 32 very rare (1%) HP:0005792
38 small thenar eminence 32 very rare (1%) HP:0001245
39 short digit 32 very rare (1%) HP:0011927
40 aplasia of the ulna 32 very rare (1%) HP:0003982
41 abnormal vertebral morphology 32 HP:0003468
42 atrioventricular block 59 Frequent (79-30%)
43 partial duplication of thumb phalanx 32 HP:0009944
44 abnormality of cardiovascular system morphology 59 Very frequent (99-80%)
45 thoracic scoliosis 32 HP:0002943
46 abnormality of the carpal bones 32 HP:0001191

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

MGI Mouse Phenotypes related to Holt-Oram Syndrome:

46 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.3 EP300 GATA4 GJA5 MYH6 MYH7 NKX2-5
2 embryo MP:0005380 10.13 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX1
3 digestive/alimentary MP:0005381 10.1 EP300 GATA4 GJA5 NKX2-5 SALL4 TBX1
4 homeostasis/metabolism MP:0005376 10.1 EP300 GATA4 GJA5 MYH6 NKX2-5 SALL4
5 growth/size/body region MP:0005378 10.09 EP300 GATA4 KAT2B NKX2-5 SALL4 TBX1
6 endocrine/exocrine gland MP:0005379 10.06 EP300 GATA4 GJA5 NKX2-5 SRSF2 TBX1
7 mortality/aging MP:0010768 10.03 EP300 GATA4 GJA5 KAT2B MYH6 NKX2-5
8 craniofacial MP:0005382 9.99 EP300 NKX2-5 SALL4 TBX1 TBX3 TGFB2
9 immune system MP:0005387 9.97 EP300 GJA5 MYH6 NKX2-5 SALL4 SRSF2
10 muscle MP:0005369 9.9 EP300 GATA4 GJA5 MYH6 MYH7 NKX2-5
11 limbs/digits/tail MP:0005371 9.8 GATA4 SALL4 TBX1 TBX3 TBX5 TGFB2
12 normal MP:0002873 9.56 EP300 GATA4 GJA5 KAT2B NKX2-5 TBX1
13 respiratory system MP:0005388 9.17 EP300 GATA4 GJA5 MYH6 NKX2-5 TBX1

Drugs & Therapeutics for Holt-Oram Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Molecular Genetic Epidemiology of Three Cardiac Defects -SCOR in Pediatric Cardiovascular Disease Completed NCT00005546

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, Kidney, Eye, Retina

Publications for Holt-Oram Syndrome

Articles related to Holt-Oram Syndrome:

(show top 50) (show all 429)
# Title Authors PMID Year
1
Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome. 9 38 4 8 71
10842287 2000
2
Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. 9 38 4 8 71
10077612 1999
3
Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. 9 38 4 8 71
8988164 1997
4
TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype. 38 4 8 71
22333898 2012
5
Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families. 9 38 8 71
12818525 2003
6
Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome. 9 38 8 71
8988165 1997
7
Variation in severity of cardiac disease in Holt-Oram syndrome. 38 4 8
8911604 1996
8
Holt-Oram syndrome: a clinical genetic study. 38 4 8
8730285 1996
9
The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) 38 4 8
8114858 1994
10
Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report. 38 4 8
2070544 1991
11
Skeletal manifestations of the Holt-Oram syndrome. 38 4 8
5410358 1970
12
Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. 9 38 8
17366586 2007
13
A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family. 9 38 8
12210327 2002
14
A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family. 4 8
2591070 1989
15
Familial heart disease with skeletal malformations. 4 8
14402857 1960
16
Tbx5-mediated expression of Ca(2+)/calmodulin-dependent protein kinase II is necessary for zebrafish cardiac and pectoral fin morphogenesis. 9 38 4
19345202 2009
17
Functional analysis of the novel TBX5 c.1333delC mutation resulting in an extended TBX5 protein. 9 38 4
18828908 2008
18
A novel TBX5 missense mutation (V263M) in a family with atrial septal defects and postaxial hexodactyly. 9 38 4
18706711 2008
19
Novel TBX5 mutations in patients with Holt-Oram syndrome. 9 38 4
17534187 2007
20
Expanding the spectrum of TBX5 mutations in Holt-Oram syndrome: detection of two intragenic deletions by quantitative real time PCR, and report of eight novel point mutations. 9 38 4
16917909 2006
21
TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome. 9 38 4
16183809 2005
22
Holt-Oram Syndrome 38 71
20301290 2004
23
Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype. 9 38 4
12789647 2003
24
Tbx5 is required for forelimb bud formation and continued outgrowth. 9 38 4
12736217 2003
25
Holt-Oram syndrome: is there a "face"? 9 38 4
12687661 2003
26
TBX5 transcription factor regulates cell proliferation during cardiogenesis. 9 38 4
11161571 2001
27
Holt-Oram syndrome with associated postaxial and central polydactyly. Further evidence for genetic heterogeneity in the Holt-Oram syndrome. 38 8
8985738 1996
28
Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome. 38 8
7820941 1994
29
Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q. 38 8
8054982 1994
30
Holt-Oram syndrome: postaxial and central polydactyly as variable manifestations in a four generations family. 38 8
8110414 1993
31
The Holt-Oram syndrome. 38 8
1870097 1991
32
Holt-Oram syndrome associated with the hypoplastic left heart syndrome. 38 8
2766565 1989
33
Prenatal ultrasound diagnosis of the Holt-Oram syndrome. 38 8
3287365 1988
34
Normal high-resolution karyotypes in three patients with the Holt-Oram syndrome. 38 8
3674114 1987
35
Holt-Oram syndrome in China: a collective review of 18 cases. 38 8
3953367 1986
36
Two patients with interstitial del (14q), one with features of Holt-Oram syndrome. Exclusion mapping of PI (alpha-1-antitrypsin). 38 8
6335371 1984
37
Holt Oram syndrome mistaken for thalidomide embryopathy--embryological considerations. 38 8
7075631 1982
38
Holt-Oram syndrome: penetrance of the gene and lack of maternal effect. 38 8
7083616 1982
39
Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome. 38 8
7449488 1981
40
Holt-Oram syndrome. 38 8
480027 1979
41
The upper limb-cardiovascular syndrome, (Holt-Oram syndrome). 38 8
1277635 1976
42
Holt-Oram syndrome associated with ectromelia and chromosomal aberrations. 38 8
5581016 1971
43
Holt-Oram syndrome: clinical and genetic study of a large family. 38 8
5904863 1966
44
Novel TBX5 duplication in a Japanese family with Holt-Oram syndrome. 38 4
25274398 2015
45
Holt Oram syndrome: a registry-based study in Europe. 38 4
25344219 2014
46
Holt-Oram syndrome with intermediate atrioventricular canal defect, and aortic coarctation: functional characterization of a de novo TBX5 mutation. 38 4
24664498 2014
47
Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease. 38 4
22543974 2012
48
Rare cardiac defect in Holt-Oram syndrome. 38 6
22447508 2012
49
Structural basis of TBX5-DNA recognition: the T-box domain in its DNA-bound and -unbound form. 38 4
20450920 2010
50
The pollicization of the index finger in the aplasia of the thumb. 38 4
20333885 2009

Variations for Holt-Oram Syndrome

ClinVar genetic disease variations for Holt-Oram Syndrome:

6 (show top 50) (show all 215)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TBX5 NM_000192.3(TBX5): c.105del (p.Ser36fs) deletion Pathogenic rs1057516042 12:114841599-114841599 12:114403794-114403794
2 TBX5 TBX5, 48-KB DUP, EX2-9DUP duplication Pathogenic
3 TGFB2 NM_003238.5(TGFB2): c.252dup (p.Arg85fs) duplication Pathogenic rs1553292112 1:218520295-218520295 1:218346953-218346953
4 TBX5 NM_000192.3(TBX5): c.668C> T (p.Thr223Met) single nucleotide variant Pathogenic rs1555225344 12:114823368-114823368 12:114385563-114385563
5 TGFB2 NM_003238.5(TGFB2): c.892_901del (p.Arg298fs) deletion Pathogenic rs1553303203 1:218609449-218609458 1:218436107-218436116
6 TBX5 NM_000192.3(TBX5): c.1158dup (p.Ser387fs) duplication Pathogenic rs1064795870 12:114793736-114793736 12:114355930-114355931
7 TGFB2 NC_000001.10: g.(?_218520024)_(218614724_?)del deletion Pathogenic 1:218520024-218614724 1:218346682-218441382
8 TBX5 NM_000192.3(TBX5): c.246_249del (p.Met83fs) deletion Pathogenic 12:114837431-114837434 12:114399626-114399629
9 TBX5 TBX5, 1491C-T single nucleotide variant Pathogenic
10 TBX5 NM_000192.3(TBX5): c.205G> T (p.Glu69Ter) single nucleotide variant Pathogenic rs104894377 12:114839668-114839668 12:114401863-114401863
11 TBX5 NM_000192.3(TBX5): c.238G> A (p.Gly80Arg) single nucleotide variant Pathogenic rs104894381 12:114839635-114839635 12:114401830-114401830
12 TBX5 NM_000192.3(TBX5): c.709C> T (p.Arg237Trp) single nucleotide variant Pathogenic rs104894382 12:114823327-114823327 12:114385522-114385522
13 TBX5 TBX5, 1-BP DEL, 416C deletion Pathogenic
14 TBX5 NM_000192.3(TBX5): c.145C> A (p.Gln49Lys) single nucleotide variant Pathogenic rs104894383 12:114841559-114841559 12:114403754-114403754
15 TBX5 NM_000192.3(TBX5): c.161T> C (p.Ile54Thr) single nucleotide variant Pathogenic rs104894384 12:114839712-114839712 12:114401907-114401907
16 TBX5 NM_000192.3(TBX5): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic rs104894379 12:114836480-114836480 12:114398675-114398675
17 TGFB2 NM_003238.5(TGFB2): c.583G> T (p.Glu195Ter) single nucleotide variant Pathogenic rs863223790 1:218607496-218607496 1:218434154-218434154
18 TBX5 NM_000192.3(TBX5): c.835C> T (p.Arg279Ter) single nucleotide variant Pathogenic rs863223788 12:114804117-114804117 12:114366312-114366312
19 TBX5 NM_000192.3(TBX5): c.444G> A (p.Trp148Ter) single nucleotide variant Pathogenic rs1555226315 12:114836444-114836444 12:114398639-114398639
20 TBX5 NM_000192.3(TBX5): c.587C> A (p.Ser196Ter) single nucleotide variant Pathogenic rs886041247 12:114832622-114832622 12:114394817-114394817
21 TBX5 NM_000192.3(TBX5): c.868C> T (p.Gln290Ter) single nucleotide variant Pathogenic 12:114804084-114804084 12:114366279-114366279
22 TBX5 GRCh37/hg19 12q24.21(chr12: 114791609-114793234) copy number loss Pathogenic 12:114791609-114793234 :0-0
23 TBX5 NM_000192.3(TBX5): c.1346del (p.Gln449fs) deletion Pathogenic 12:114793548-114793548 12:114355743-114355743
24 TBX5 NM_000192.3(TBX5): c.1303del (p.Leu435fs) deletion Pathogenic 12:114793591-114793591 12:114355786-114355786
25 TBX5 NM_000192.3(TBX5): c.1269C> G (p.Tyr423Ter) single nucleotide variant Pathogenic 12:114793625-114793625 12:114355820-114355820
26 TBX5 NM_000192.3(TBX5): c.1203G> A (p.Trp401Ter) single nucleotide variant Pathogenic 12:114793691-114793691 12:114355886-114355886
27 TBX5 NM_000192.3(TBX5): c.1084C> T (p.Gln362Ter) single nucleotide variant Pathogenic 12:114793810-114793810 12:114356005-114356005
28 TBX5 NM_000192.3(TBX5): c.1074del (p.Pro359fs) deletion Pathogenic 12:114793820-114793820 12:114356015-114356015
29 TBX5 NM_000192.3(TBX5): c.1045G> T (p.Glu349Ter) single nucleotide variant Pathogenic 12:114793849-114793849 12:114356044-114356044
30 TBX5 NM_000192.3(TBX5): c.978del (p.Glu328fs) deletion Pathogenic 12:114803974-114803974 12:114366169-114366169
31 TBX5 NM_000192.3(TBX5): c.943C> T (p.Gln315Ter) single nucleotide variant Pathogenic 12:114804009-114804009 12:114366204-114366204
32 TBX5 NM_000192.3(TBX5): c.933C> G (p.Tyr311Ter) single nucleotide variant Pathogenic 12:114804019-114804019 12:114366214-114366214
33 TBX5 NM_000192.3(TBX5): c.924del (p.Asn309fs) deletion Pathogenic 12:114804028-114804028 12:114366223-114366223
34 TBX5 NM_000192.3(TBX5): c.879T> A (p.Cys293Ter) single nucleotide variant Pathogenic 12:114804073-114804073 12:114366268-114366268
35 TBX5 NM_000192.3(TBX5): c.845C> T (p.Ser282Phe) single nucleotide variant Pathogenic 12:114804107-114804107 12:114366302-114366302
36 TBX5 NM_000192.3(TBX5): c.728_729del (p.Glu243fs) deletion Pathogenic 12:114823307-114823308 12:114385502-114385503
37 TBX5 NM_000192.3(TBX5): c.713dup (p.Ser239fs) duplication Pathogenic 12:114823323-114823323 12:114385518-114385518
38 TBX5 NM_000192.3(TBX5): c.703G> T (p.Gly235Ter) single nucleotide variant Pathogenic 12:114823333-114823333 12:114385528-114385528
39 TBX5 NM_000192.3(TBX5): c.680_683del (p.Ile227fs) deletion Pathogenic 12:114823353-114823356 12:114385548-114385551
40 TBX5 NM_000192.3(TBX5): c.674T> G (p.Leu225Ter) single nucleotide variant Pathogenic 12:114823362-114823362 12:114385557-114385557
41 TBX5 NM_000192.3(TBX5): c.633_634TA[1] (p.Ile212fs) short repeat Pathogenic 12:114832573-114832574 12:114394768-114394769
42 TBX5 NM_000192.3(TBX5): c.593dup (p.Asn198fs) duplication Pathogenic 12:114832616-114832616 12:114394811-114394811
43 TBX5 NM_000192.3(TBX5): c.559_572dup (p.Asn191fs) duplication Pathogenic 12:114832637-114832650 12:114394832-114394845
44 TBX5 NM_000192.3(TBX5): c.537C> A (p.Tyr179Ter) single nucleotide variant Pathogenic 12:114832672-114832672 12:114394867-114394867
45 TBX5 NM_000192.3(TBX5): c.500del (p.Pro167fs) deletion Pathogenic 12:114836388-114836388 12:114398583-114398583
46 TBX5 NM_000192.3(TBX5): c.496del (p.Asp166fs) deletion Pathogenic 12:114836392-114836392 12:114398587-114398587
47 TBX5 NM_000192.3(TBX5): c.457dup (p.Val153fs) duplication Pathogenic 12:114836430-114836431 12:114398625-114398626
48 TBX5 NM_000192.3(TBX5): c.426del (p.Ala143fs) deletion Pathogenic 12:114836462-114836462 12:114398657-114398657
49 TBX5 NM_000192.3(TBX5): c.342C> A (p.Tyr114Ter) single nucleotide variant Pathogenic 12:114837338-114837338 12:114399533-114399533
50 TBX5 NM_000192.3(TBX5): c.336del (p.His112fs) deletion Pathogenic 12:114837344-114837344 12:114399539-114399539

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

74
# 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

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 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.59 TGFB2 NKX2-5 GATA4 EP300
2
Show member pathways
12.56 TBX5 NKX2-5 MYH6 KAT2B GATA4
3
Show member pathways
12.1 TGFB2 TBX5 NKX2-5 MYH7 GATA4
4
Show member pathways
11.98 TGFB2 MYH7 MYH6
5
Show member pathways
11.81 TBX5 NKX2-5 KAT2B GATA4 EP300
6 11.79 TBX5 NKX2-5 GATA4
7 11.77 TGFB2 KAT2B EP300
8 11.74 MYH6 KAT2B GATA4 EP300
9 11.54 NKX2-5 KAT2B EP300
10 11.43 TGFB2 KAT2B EP300
11 11.14 TGFB2 NKX2-5 GATA4 EP300
12 10.98 TBX5 NKX2-5 MYH6 GATA4
13 10.84 NKX2-5 MYH7 GATA4
14 10.59 TBX5 TBX1 NKX2-5 GATA4
15 10.18 NKX2-5 GATA4

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 TBX5 SALL4 NKX2-5 KAT2B EP300
2 myosin filament GO:0032982 9.26 MYH7 MYH6
3 muscle myosin complex GO:0005859 9.16 MYH7 MYH6
4 protein-DNA complex GO:0032993 8.8 TBX5 NKX2-5 EP300

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

(show top 50) (show all 52)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.95 TBX5 TBX3 TBX1 NKX2-5 KAT2B GATA4
2 in utero embryonic development GO:0001701 9.88 TBX3 SALL4 MYH6
3 skeletal system development GO:0001501 9.87 TGFB2 TBX3 GJA5
4 heart looping GO:0001947 9.8 TBX3 NKX2-5 GATA4
5 embryonic limb morphogenesis GO:0030326 9.78 TGFB2 TBX5 SALL4 GJA5
6 blood vessel development GO:0001568 9.77 TBX3 TBX1 GJA5
7 positive regulation of Notch signaling pathway GO:0045747 9.76 TGFB2 KAT2B EP300
8 outflow tract morphogenesis GO:0003151 9.76 TBX3 TBX1 NKX2-5 GJA5
9 cardiac muscle contraction GO:0060048 9.75 NKX2-5 MYH7 MYH6
10 heart morphogenesis GO:0003007 9.73 TGFB2 TBX3 TBX1 NKX2-5
11 regulation of heart rate GO:0002027 9.71 MYH7 MYH6
12 positive regulation of gene expression, epigenetic GO:0045815 9.71 KAT2B EP300
13 outflow tract septum morphogenesis GO:0003148 9.71 TGFB2 TBX1 NKX2-5
14 embryonic forelimb morphogenesis GO:0035115 9.7 TBX5 TBX3
15 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.7 MYH7 MYH6
16 thyroid gland development GO:0030878 9.7 TBX1 NKX2-5
17 artery morphogenesis GO:0048844 9.69 TBX1 GJA5
18 regulation of cardiac muscle contraction GO:0055117 9.69 NKX2-5 GJA5
19 embryonic heart tube development GO:0035050 9.69 TBX3 NKX2-5 GJA5
20 regulation of the force of heart contraction GO:0002026 9.68 MYH7 MYH6
21 positive regulation of transcription of Notch receptor target GO:0007221 9.68 KAT2B EP300
22 pharyngeal system development GO:0060037 9.68 TBX1 NKX2-5
23 ventricular trabecula myocardium morphogenesis GO:0003222 9.68 TGFB2 NKX2-5
24 striated muscle contraction GO:0006941 9.67 MYH7 MYH6
25 animal organ morphogenesis GO:0009887 9.67 TBX3 EP300
26 cardiac muscle hypertrophy in response to stress GO:0014898 9.67 MYH7 MYH6
27 adult heart development GO:0007512 9.67 NKX2-5 MYH7 MYH6
28 ventricular septum morphogenesis GO:0060412 9.67 TGFB2 TBX3 NKX2-5 GJA5
29 protein acetylation GO:0006473 9.66 KAT2B EP300
30 cardiac right ventricle morphogenesis GO:0003215 9.66 TGFB2 GATA4
31 cardiac muscle cell proliferation GO:0060038 9.65 TGFB2 NKX2-5
32 endocardial cushion development GO:0003197 9.65 TBX5 GATA4
33 atrioventricular valve morphogenesis GO:0003181 9.65 TGFB2 TBX5
34 forelimb morphogenesis GO:0035136 9.64 TBX5 TBX3
35 cardiac ventricle morphogenesis GO:0003208 9.64 NKX2-5 GATA4
36 positive regulation of heart contraction GO:0045823 9.63 TGFB2 NKX2-5
37 atrial septum development GO:0003283 9.63 TBX5 GJA5
38 peptidyl-lysine acetylation GO:0018394 9.62 KAT2B EP300
39 ventricular septum development GO:0003281 9.62 TBX5 SALL4 GJA5 GATA4
40 internal peptidyl-lysine acetylation GO:0018393 9.61 KAT2B EP300
41 cardiac conduction system development GO:0003161 9.61 NKX2-5 GJA5
42 atrial septum primum morphogenesis GO:0003289 9.6 TGFB2 GATA4
43 N-terminal peptidyl-lysine acetylation GO:0018076 9.57 KAT2B EP300
44 bundle of His development GO:0003166 9.56 TBX5 NKX2-5
45 cardiac muscle cell differentiation GO:0055007 9.56 TBX5 TBX3 NKX2-5 GATA4
46 positive regulation of cardioblast differentiation GO:0051891 9.46 TGFB2 TBX5 NKX2-5 GATA4
47 tissue development GO:0009888 9.39 SALL4
48 atrial septum morphogenesis GO:0060413 9.35 TGFB2 TBX5 NKX2-5 GJA5 GATA4
49 heart development GO:0007507 9.23 TGFB2 TBX5 TBX1 SALL4 NKX2-5 KAT2B
50 regulation of transcription, DNA-templated GO:0006355 10.13 TBX5 TBX3 TBX1 SALL4 NKX2-5 KAT2B

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity GO:0003700 9.91 TBX5 TBX3 TBX1 NKX2-5 GATA4
2 sequence-specific DNA binding GO:0043565 9.8 TBX5 TBX3 TBX1 NKX2-5 GATA4
3 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.72 TBX5 TBX3 NKX2-5 GATA4 EP300
4 acetyltransferase activity GO:0016407 9.49 KAT2B EP300
5 microfilament motor activity GO:0000146 9.46 MYH7 MYH6
6 actin-dependent ATPase activity GO:0030898 9.43 MYH7 MYH6
7 RNA polymerase II transcription factor binding GO:0001085 9.43 TBX3 GATA4 EP300
8 lysine N-acetyltransferase activity, acting on acetyl phosphate as donor GO:0004468 9.37 KAT2B EP300
9 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.26 TBX5 NKX2-5 GATA4 EP300
10 peptide-lysine-N-acetyltransferase activity GO:0061733 9.16 KAT2B EP300
11 transcription factor binding GO:0008134 9.1 TBX5 SALL4 NKX2-5 KAT2B GATA4 EP300
12 DNA binding GO:0003677 10.02 TBX5 TBX3 TBX1 SALL4 NKX2-5 GATA4
13 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 10 TBX5 TBX3 TBX1 SALL4 NKX2-5 GATA4

Sources for Holt-Oram Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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