Congenital heart disease (CHD) is worldwide a major threat for children below the age of five, it has high mortality and morbidity ratio. The number is increasing 5% every year in USA, where figures are scanty in our population. Introduction: In Pakistan, the adult population with congenital heart diseases is increasing and consanguineous marriages, a custom in region in also playing a role in increasing CHDs. In our study we look social and genetic aspects for these diseases. Nkx 2.5, a transcription factor and first progenitor in cardiac formation. (Olson E. and Srivastava D., 1996) to date, no data is available about the mutations in this gene responsible for CHD in Pakistani population. Nkx 2.5 gene encodes 324 aa. contains a homeodomain (142-200aa) which is highly conserved among vertebrates. Materials and Methods: A cohort of 225, CHD patients who were registered at National Institute of Cardiovascular Diseases (NICVD) from 2005-2008 were included in the study; these are non syndromic and sporadic cases. Informed consents and detail family history was obtained. The cohort contains Atrial Septal Defect (ASD), Ventricular Septal Defects (VSD), Tetralogy of Fallot (TOF), Patent Ductus Arteriosus (PDA) and Dextro transposition of Great Arteries (DTGA). Control group (n= 120) is healthy unrelated individuals with mean age 4± 2.0. DNA was extracted and NKx 2.5 gene was amplified and sequenced to check mutations. (McElhinney, D. B., 2003) Results: CHD patients (n=225, 57% male and 43% female). Age ranges 0.001-17 yrs. mean age is 4.45 ± 3.5. More than 40 mutations are reported till date (Liu XY., et al, 2011). Our findings were five SNPs in our population. Out of these two are missense, two are in 5’UTR region and one is inframe deletion. These mutations are potent in damaging protein structure predicted by SIFT, mutation taster and polyphen. Discussion: CHD is a major cause of child death in the first year of life. Our study concludes a few aspects and will broaden it to other genes as it is a need to find aetiology of these diseases and to combat it with the modern genetic therapeutics.