Sardar Syed Lal Darwaish was killed in the volatile Orangi Town while he was returning home from office, police said.
Darwaish was a close relative of Senator Shahi Syed who heads the ANP in Karachi, a party spokesperson said.
In the past also, several ANP leaders have been targeted in the city which has a big Pashtun speaking population as many of them migrated from the northern areas or Khyber Pakhtunkhwa province due to the rising incidents of terrorism and religious intolerance.
Sharif returned from Karachi after ordering the provincial Sindh government and paramilitary Rangers to carry out effective operations in troubled areas of the city hit by criminal gangs and terrorists.
During different raids conducted by the security forces today, a total of 25 people were arrested, including seven target killers, four extortionists and a few members of political parties and banned outfits.