The tomb was ransacked at the start of the Palestinian uprising in 2000
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Seven Israelis were injured when Palestinian gunmen opened fire on their car near the West Bank city of Nablus, Israeli military sources said.
One of the wounded was in a critical condition and all were evacuated for treatment, the sources added.
The shooting reportedly happened near the disputed holy site Joseph's Tomb.
The army has banned Jewish pilgrims from visiting the tomb - which they say is the burial site of a biblical patriarch - for security reasons.
"All the wounded have been evacuated to hospital and the defence forces are carrying out a search of the area," a security source was quoted by Reuters as saying.
"They had not asked for permission to visit the site".
Palestinian residents in Nablus said the Israeli army had sealed off the area where the shooting took place.
Military escort
A Jewish seminary was built at Joseph's tomb in the 1980s but it was evacuated by the Israeli army in October 2000, following heavy fighting in the early weeks of the Palestinian uprising.
It was later rebuilt by the Palestinians as a mosque.
Many Jews believe the site to be the final resting place of the biblical patriarch Joseph.
Muslims hold that an Islamic cleric, Sheikh Yousef Dawiqat, was buried at the site two centuries ago.
Jewish settlers now need a military escort to visit the site, although some still try to make it by themselves to pray there.