diff --git a/ontobio/io/qc.py b/ontobio/io/qc.py
index 14cd685d..1e98761c 100644
--- a/ontobio/io/qc.py
+++ b/ontobio/io/qc.py
@@ -33,7 +33,9 @@
 iba_eco = ecomapping.coderef_to_ecoclass("IBA")
 iep_eco = ecomapping.coderef_to_ecoclass("IEP")
 hep_eco = ecomapping.coderef_to_ecoclass("HEP")
-
+iss_eco = ecomapping.coderef_to_ecoclass("ISS")
+isa_eco = ecomapping.coderef_to_ecoclass("ISA")
+iso_eco = ecomapping.coderef_to_ecoclass("ISO")
 
 # TestResult = collections.namedtuple("TestResult", ["result_type", "message", "result"])
 class TestResult(object):
@@ -896,6 +898,21 @@ def test(self, annotation: association.GoAssociation, config: assocparser.AssocP
         return TestResult(repair_result(repair_state, self.fail_mode), "{}: {} should be one of {}. Repaired to {}".format(self.message(repair_state), relation, allowed_str, repaired_str), repaired_annotation)
 
 
+class GoRule63(GoRule):
+
+    def __init__(self):
+        super().__init__("GORULE:0000063", "Annotations using ISS/ISA/ISO evidence should refer to a gene product (in the 'with' column)", FailMode.HARD)
+
+    def test(self, annotation: association.GoAssociation, config: assocparser.AssocParserConfig, group=None) -> TestResult:
+        evidence = str(annotation.evidence.type)
+        withfrom = annotation.evidence.with_support_from
+
+
+        if evidence in [iss_eco, isa_eco, iso_eco] and (withfrom is None or len(withfrom) == 0):
+            return self._result(False)
+
+        return self._result(True)
+
 GoRules = enum.Enum("GoRules", {
     "GoRule02": GoRule02(),
     "GoRule06": GoRule06(),
@@ -920,6 +937,7 @@ def test(self, annotation: association.GoAssociation, config: assocparser.AssocP
     "GoRule55": GoRule55(),
     "GoRule58": GoRule58(),
     "GoRule61": GoRule61(),
+    "GoRule63": GoRule63(),
     # GoRule13 at the bottom in order to make all other rules clean up an annotation before reaching 13
     "GoRule13": GoRule13()
 })
diff --git a/tests/test_qc.py b/tests/test_qc.py
index 54d05db8..af02f98c 100644
--- a/tests/test_qc.py
+++ b/tests/test_qc.py
@@ -722,7 +722,37 @@ def test_gorule61():
                             version="2.2")
     test_result = qc.GoRule61().test(assoc.associations[0], config)
     assert test_result.result_type == qc.ResultType.PASS
+        
+def test_go_rule_63():
+    # ISS with anything in withfrom
+    assoc = make_annotation(evidence="ISS", withfrom="BLAH:12345").associations[0]
+    test_result = qc.GoRule63().test(assoc, all_rules_config())
+    assert test_result.result_type == qc.ResultType.PASS
+
+    # ISA with anything in withfrom
+    assoc = make_annotation(evidence="ISA", withfrom="BLAH:12345").associations[0]
+    test_result = qc.GoRule63().test(assoc, all_rules_config())
+    assert test_result.result_type == qc.ResultType.PASS
+    
+    # ISO with anything in withfrom
+    assoc = make_annotation(evidence="ISO", withfrom="BLAH:12345").associations[0]
+    test_result = qc.GoRule63().test(assoc, all_rules_config())
+    assert test_result.result_type == qc.ResultType.PASS    
 
+    # ISS with nothing in withfrom
+    assoc = make_annotation(evidence="ISS", withfrom="").associations[0]
+    test_result = qc.GoRule63().test(assoc, all_rules_config())
+    assert test_result.result_type == qc.ResultType.ERROR
+
+    # ISA with  with nothing in withfrom
+    assoc = make_annotation(evidence="ISA", withfrom="").associations[0]
+    test_result = qc.GoRule63().test(assoc, all_rules_config())
+    assert test_result.result_type == qc.ResultType.ERROR
+    
+    # ISO with  with nothing in withfrom
+    assoc = make_annotation(evidence="ISO", withfrom="").associations[0]
+    test_result = qc.GoRule63().test(assoc, all_rules_config())
+    assert test_result.result_type == qc.ResultType.ERROR
 
 def test_all_rules():
     # pass
@@ -739,7 +769,7 @@ def test_all_rules():
     assoc = gafparser.to_association(a).associations[0]
 
     test_results = qc.test_go_rules(assoc, config).all_results
-    assert len(test_results.keys()) == 23
+    assert len(test_results.keys()) == 24
     assert test_results[qc.GoRules.GoRule26.value].result_type == qc.ResultType.PASS
     assert test_results[qc.GoRules.GoRule29.value].result_type == qc.ResultType.PASS