diff --git a/go/test/endtoend/vtgate/lookup_test.go b/go/test/endtoend/vtgate/lookup_test.go
index 444b7fb150b..c34ac6de527 100644
--- a/go/test/endtoend/vtgate/lookup_test.go
+++ b/go/test/endtoend/vtgate/lookup_test.go
@@ -21,9 +21,9 @@ import (
 	"fmt"
 	"testing"
 
-	"github.com/stretchr/testify/assert"
+	"github.com/google/go-cmp/cmp"
 
-	"vitess.io/vitess/go/test/utils"
+	"github.com/stretchr/testify/assert"
 
 	"github.com/stretchr/testify/require"
 
@@ -516,19 +516,33 @@ func TestSelectNull(t *testing.T) {
 	exec(t, conn, "begin")
 	exec(t, conn, "insert into t5_null_vindex(id, idx) values(1, 'a'), (2, 'b'), (3, null)")
 	exec(t, conn, "commit")
-	qr := exec(t, conn, "select id, idx from t5_null_vindex order by id")
-	utils.MustMatch(t, fmt.Sprintf("%v", qr.Rows), "[[INT64(1) VARCHAR(\"a\")] [INT64(2) VARCHAR(\"b\")] [INT64(3) NULL]]", "")
 
-	qr = exec(t, conn, "select id, idx from t5_null_vindex where idx = null")
-	require.Empty(t, qr.Rows)
+	assertMatches(t, conn, "select id, idx from t5_null_vindex order by id", "[[INT64(1) VARCHAR(\"a\")] [INT64(2) VARCHAR(\"b\")] [INT64(3) NULL]]")
+	assertIsEmpty(t, conn, "select id, idx from t5_null_vindex where idx = null")
+	assertMatches(t, conn, "select id, idx from t5_null_vindex where idx is null", "[[INT64(3) NULL]]")
+	assertMatches(t, conn, "select id, idx from t5_null_vindex where idx is not null order by id", "[[INT64(1) VARCHAR(\"a\")] [INT64(2) VARCHAR(\"b\")]]")
+	assertIsEmpty(t, conn, "select id, idx from t5_null_vindex where id IN (null)")
+	assertMatches(t, conn, "select id, idx from t5_null_vindex where id IN (1,2,null) order by id", "[[INT64(1) VARCHAR(\"a\")] [INT64(2) VARCHAR(\"b\")]]")
+	assertIsEmpty(t, conn, "select id, idx from t5_null_vindex where id NOT IN (1,null) order by id")
+	assertMatches(t, conn, "select id, idx from t5_null_vindex where id NOT IN (1,3)", "[[INT64(2) VARCHAR(\"b\")]]")
 
-	qr = exec(t, conn, "select id, idx from t5_null_vindex where idx is null")
-	utils.MustMatch(t, fmt.Sprintf("%v", qr.Rows), "[[INT64(3) NULL]]", "")
+	exec(t, conn, "delete from t5_null_vindex")
+}
 
-	qr = exec(t, conn, "select id, idx from t5_null_vindex where idx is not null order by id")
-	utils.MustMatch(t, fmt.Sprintf("%v", qr.Rows), "[[INT64(1) VARCHAR(\"a\")] [INT64(2) VARCHAR(\"b\")]]", "")
+func assertMatches(t *testing.T, conn *mysql.Conn, query, expected string) {
+	t.Helper()
+	qr := exec(t, conn, query)
+	got := fmt.Sprintf("%v", qr.Rows)
+	diff := cmp.Diff(expected, got)
+	if diff != "" {
+		t.Errorf("Query: %s (-want +got):\n%s", query, diff)
+	}
+}
 
-	exec(t, conn, "delete from t5_null_vindex")
+func assertIsEmpty(t *testing.T, conn *mysql.Conn, query string) {
+	t.Helper()
+	qr := exec(t, conn, query)
+	assert.Empty(t, qr.Rows)
 }
 
 func exec(t *testing.T, conn *mysql.Conn, query string) *sqltypes.Result {
diff --git a/go/vt/vtgate/planbuilder/route_option.go b/go/vt/vtgate/planbuilder/route_option.go
index c38c163231e..4543f065f8a 100644
--- a/go/vt/vtgate/planbuilder/route_option.go
+++ b/go/vt/vtgate/planbuilder/route_option.go
@@ -258,6 +258,8 @@ func (ro *routeOption) computePlan(pb *primitiveBuilder, filter sqlparser.Expr)
 			return ro.computeEqualPlan(pb, node)
 		case sqlparser.InStr:
 			return ro.computeINPlan(pb, node)
+		case sqlparser.NotInStr:
+			return ro.computeNotInPlan(node.Right), nil, nil
 		}
 	case *sqlparser.IsExpr:
 		return ro.computeISPlan(pb, node)
@@ -316,6 +318,10 @@ func (ro *routeOption) computeINPlan(pb *primitiveBuilder, comparison *sqlparser
 	}
 	switch node := comparison.Right.(type) {
 	case sqlparser.ValTuple:
+		if len(node) == 1 && sqlparser.IsNull(node[0]) {
+			return engine.SelectNone, nil, nil
+		}
+
 		for _, n := range node {
 			if !ro.exprIsValue(n) {
 				return engine.SelectScatter, nil, nil
@@ -328,6 +334,20 @@ func (ro *routeOption) computeINPlan(pb *primitiveBuilder, comparison *sqlparser
 	return engine.SelectScatter, nil, nil
 }
 
+// computeNotInPlan looks for null values to produce a SelectNone if found
+func (*routeOption) computeNotInPlan(right sqlparser.Expr) engine.RouteOpcode {
+	switch node := right.(type) {
+	case sqlparser.ValTuple:
+		for _, n := range node {
+			if sqlparser.IsNull(n) {
+				return engine.SelectNone
+			}
+		}
+	}
+
+	return engine.SelectScatter
+}
+
 var planCost = map[engine.RouteOpcode]int{
 	engine.SelectUnsharded:   0,
 	engine.SelectNext:        0,
diff --git a/go/vt/vtgate/planbuilder/testdata/filter_cases.txt b/go/vt/vtgate/planbuilder/testdata/filter_cases.txt
index 74a3c7fa9a2..6ad9e9fc09c 100644
--- a/go/vt/vtgate/planbuilder/testdata/filter_cases.txt
+++ b/go/vt/vtgate/planbuilder/testdata/filter_cases.txt
@@ -1351,3 +1351,61 @@
     "Table": "music"
   }
 }
+
+# Single table with unique vindex match and IN (null)
+"select id from music where user_id = 4 and id IN (null)"
+{
+  "QueryType": "SELECT",
+  "Original": "select id from music where user_id = 4 and id IN (null)",
+  "Instructions": {
+    "OperatorType": "Route",
+    "Variant": "SelectNone",
+    "Keyspace": {
+      "Name": "user",
+      "Sharded": true
+    },
+    "FieldQuery": "select id from music where 1 != 1",
+    "Query": "select id from music where user_id = 4 and id in (null)",
+    "Table": "music"
+  }
+}
+
+# Single table with unique vindex match and IN (null, 1, 2)
+"select id from music where user_id = 4 and id IN (null, 1, 2)"
+{
+  "QueryType": "SELECT",
+  "Original": "select id from music where user_id = 4 and id IN (null, 1, 2)",
+  "Instructions": {
+    "OperatorType": "Route",
+    "Variant": "SelectEqualUnique",
+    "Keyspace": {
+      "Name": "user",
+      "Sharded": true
+    },
+    "FieldQuery": "select id from music where 1 != 1",
+    "Query": "select id from music where user_id = 4 and id in (null, 1, 2)",
+    "Table": "music",
+    "Values": [
+      4
+    ],
+    "Vindex": "user_index"
+  }
+}
+
+# Single table with unique vindex match and NOT IN (null, 1, 2)
+"select id from music where user_id = 4 and id NOT IN (null, 1, 2)"
+{
+  "QueryType": "SELECT",
+  "Original": "select id from music where user_id = 4 and id NOT IN (null, 1, 2)",
+  "Instructions": {
+    "OperatorType": "Route",
+    "Variant": "SelectNone",
+    "Keyspace": {
+      "Name": "user",
+      "Sharded": true
+    },
+    "FieldQuery": "select id from music where 1 != 1",
+    "Query": "select id from music where user_id = 4 and id not in (null, 1, 2)",
+    "Table": "music"
+  }
+}