Connection Getting Timed Out When Sending Request to Expressjs App on EC2

I have an expessjs app running on EC2 on port 5000.

I am able to successfully send request to the EC2 directly via its public Ipv4 like http://54.125.456:5000/.

But when I set up IPv4 as an A record of a custom domain hosted on Route 53 with SSL certificate issued from ACM, and then send the request from the browser through custom domain like https://example.com/, I get ERR_CONNECTION_TIMEOUT error

I have checked the security group of the EC2. All the ports 80, 22 and 443 are opened for inbound traffic. I have even run the expressjs app without reverse-proxy server nginx and only using PM2 or nodemon like https://example.com:5000 but the issue is there. I am unable to resolve the issue. Help would be appreciated

It sounds like you don't have anything listening for and terminating TLS traffic. So even though you have port 443 open, there's nothing on your EC2 instance handling the traffic (assuming "only using PM2 or nodemon").

Even if you're using nginx - ACM issued certs aren't exportable so that can't be configured to terminate your TLS traffic using an ACM issued cert.

To use an ACM issued cert you'll need to integrate with a compatible service. For example, you could deploy an Application Load Balancer, have that terminate your TLS traffic, and forward web traffic on to your EC2 instance. You'll also then be able to move your EC2 instance into a private subnet rather than exposing it directly to the internet.