Full data view for gene KNG1

Information The variants shown are described using the NM_001102416.2 transcript reference sequence.

40 entries on 1 page. Showing entries 1 - 40.
Legend   How to query  

Effect     
Exon     
AscendingDNA change (cDNA)     
RNA change     
Protein     
Allele     
Classification method     
Clinical classification     
DNA change (genomic) (hg19)     
DNA change (hg38)     
Published as     
ISCN     
DB-ID     
Variant remarks     
Reference     
ClinVar ID     
dbSNP ID     
Origin     
Segregation     
Frequency     
Re-site     
VIP     
Methylation     
Template     
Technique     
Tissue     
Remarks     
Disease     
ID_report     
Reference     
Remarks     
Gender     
Consanguinity     
Country     
Population     
Age at death     
VIP     
Data_av     
Treatment     
Panel size     
Owner     
?/. _1 c.-85T>A r.(=) p.(=) Unknown - VUS g.186435247T>A g.186717458T>A - - KNG1_000002 - Journal: Loules 2020 ClinVar-VCV000827589.1 rs1579107719 Germline - - - - - DNA SEQ-NG-IT - - HAE6 - Journal: Loules 2020 - - - - - - - - - 1 Christian Drouet
?/. 1 c.166T>G r.(?) p.(Leu56Val) Unknown - VUS g.186435497T>G g.186717708T>G - - KNG1_000019 Introduced in ClinVar as VUS by Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein - ClinVar-SCV003807556.1 - Germline - - - - - DNA ? blood - HAE6 - - - - - Brazil - - - - - 1 Christian Drouet
+/. 2i c.306+2T>A r.spl p.? Both (homozygous) - pathogenic (recessive) g.186438006T>A g.186720217T>A c.[306+2T>A];[306+2T>A] - KNG1_000009 His daughter and his son display a normal aPTT. Laboratory analyses show normal or increased levels of the intrinsic pathway factors, and decreased PK and HK. Introduced in ClinVar as pathogenic by Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Germany Journal: Adenaeuer 2023 ClinVar-SCV004031439.1 - Germline - - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Adenaeuer 2023 - - - Italy - - - - - 3 Christian Drouet
?/. 4 c.421G>A r.(?) p.(Asp141Asn) Unknown - VUS g.186442906G>A g.186725117G>A - - KNG1_000003 - Journal: Loules 2020 ClinVar-VCV000827590.1 rs1579116763 Germline - 0.0 (0/10680; ALFA Project) - - - DNA SEQ-NG-IT - - HAE6 - Journal: Loules 2020 - - - - - - - - - 1 Christian Drouet
+/. 4 c.460C>A r.(?) p.(Pro154Thr) Both (homozygous) - pathogenic (recessive) g.186442945C>A g.186725156C>A - - KNG1_000023 - Journal: Chen 2024 - - Germline yes - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Chen 2024 - F - China - - - - - 6 Christian Drouet
+/. 4 c.488del r.(?) p.(Gly163Alafs*20) Parent #1 - pathogenic g.186442973del g.186725184del c.[488del];[1165C>T] - KNG1_000012 Compound c.[488del];[1165C>T] variants abolish expression of HK and LK and function of HK Journal: Jeung 2020 Journal: Adenaeuer 2022 - - Germline - - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Jeung 2020 - M - Korea - - - - - 1 Christian Drouet
+/. 4 c.523_524dup r.(?) p.(Leu176Profs*8) Both (homozygous) - pathogenic g.186443008_186443009dup g.186725219_186725220dup c.[523_524dup];[523_524dup] - KNG1_000013 Proband homozygous carrier of c.[523_524dup];[523_524dup] variants does not express both HK and LK proteins HK activity is also reduced in the plasma of proband's three heterozygous children Journal: Fukushima 2014 Journal: Adenaeuer 2022 - - Germline yes - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Fukushima 2022 Homozygous proband with his three heterozygous children M - Japan - - - - - 4 Christian Drouet
+/. 5 c.586C>T r.(?) p.(Arg196*) Both (homozygous) - pathogenic (recessive) g.186445047C>T g.186727258C>T c.[c.586C>T];[c.586C>T] - KNG1_000010 Intrinsic coagulation factors were within the reference range except for a borderline decreased FXI:C and PK:C, and a strongly decreased HK:C, indicating total HK deficiency. c.586C>T variant affects HK and LK expression. Considered pathogenic by Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Germany Journal: Nazir 2019 Journal: Adenaeuer 2022 ClinVar-VCV000000572.1 rs121918131 Germline - 0.00001061 (gnomAD) - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Nazir 2019 - F - Oman - - - - - 1 Christian Drouet
+/. 5 c.586C>T r.(?) p.(Arg196*) Both (homozygous) - pathogenic (recessive) g.186445047C>T g.186727258C>T c.[c.586C>T];[c.586C>T] - KNG1_000010 Proband sample displays normal levels of intrinsic coagulation factors, except for a slightly decreased FXI:C and PK:C, and a strongly decreased HK:C, indicating total HK deficiency. c.586C>T variant affects HK and LK expression. Journal: Hayashi 1990 Journal: Adenaeuer 2022 ClinVar-VCV000000572.1 rs121918131 Germline - 0.00001061 (gnomAD) - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Hayashi 1990 Undetectable plasma antigenic HK F likely Japan - - - - - 4 Christian Drouet
+/. 5 c.586C>T r.(?) p.(Arg196*) Both (homozygous) - pathogenic g.186445047C>T g.186727258C>T c.[586C>T];[586C>T] - KNG1_000010 Proband plasma presenting with a complete deficit of HK and LK PubMed: Ishimaru 1999 Journal: Adenaeuer 2022 ClinVar-VCV000000572.1 rs121918131 Germline - 0.00001061 (gnomAD) - - - DNA SEQ blood - high molecular weight kininogen deficiency - PubMed: Ishimaru 1999 - F - Japan - - - - - 1 Christian Drouet
-/. 5 c.587G>A r.(?) p.(Arg196Gln) Unknown - likely benign (!) g.186445048G>A g.186727259G>A - - KNG1_000008 p.(Arg196Gln) variant in the cystatin kininogen-type 2 (151-254) Introduced as likely benign with the following ACMG criteria PM1, PM1, BP1, BP2 - - rs144123648 Unknown - 0.0004597 - - - DNA ? - - Healthy/Control - - - - - - - - - - - 1 Christian Drouet
-?/. - c.587G>A r.(?) p.(Arg196Gln) Unknown - likely benign g.186445048G>A - KNG1(NM_001102416.3):c.587G>A (p.R196Q) - KNG1_000008 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. 5 c.618T>G r.(?) p.(Cys206Trp) Parent #1 ACMG likely pathogenic g.186445079T>G g.186727290T>G c.[618T>G](;)[1165C>T] - KNG1_000024 Compound heterozygous female carrier both c.618T>G and c.1165C>T. c.618T>G variant disrupts the disulfide bond between Cys206 and Cys218; c.1165C>T is a non-sense variant with truncation of the D5 domain of the protein. Journal: Lv 2025 - - Germline - - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Lv 2025 Single family with a compound heterozygous affected individual F no China - - - - - 1 Christian Drouet
+?/. 5 c.654C>A r.(?) p.(Cys218*) Unknown - VUS (!) g.186445115C>A g.186727326C>A - - KNG1_000020 Variant provisionally introduced; position must be confirmed by authors. Variant provisionally introduced as VUS pending a demonstration as causative for HAE-nC1-INH Journal: Dias de Castro 2024 - - Germline - - - - - DNA SEQ blood - HAE3 - Journal: Dias de Castro 2024 - - no Portugal - - - - - 38 Christian Drouet
+/. 6 c.718C>T r.(?) p.(Arg240*) Paternal (confirmed) - pathogenic (recessive) g.186449379C>T g.186731590C>T c.[718C>T];[1038+1G>A] - KNG1_000011 A German kindred with a female symptomatic carrier of compound variants c.[718C>T];[1038+1G>A], with abolished expression of HK and LK, and her asymptomatic heterozygous parents Journal: Adenaeuer 2022 ClinVar-SCV004031437.1 rs761496908 Germline - 0.000006206 - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Adenaeuer 2022 - F - Germany - - - - - 3 Christian Drouet
+?/. - c.744T>A r.(?) p.(Cys248*) Unknown ACMG likely benign g.186449405T>A g.186731616T>A - - KNG1_000027 Asymptomatic parents, suggesting a possible de novo case. Journal: Dias de Castro 2024 - - Germline/De novo (untested) - - - - - DNA SEQ blood - HAE6 - Journal: Dias de Castro 2024 - F no Portugal - - - - - 1 Christian Drouet
+/. 8i c.1038+1G>A r.spl p.? Maternal (confirmed) - pathogenic (recessive) g.186456996G>A g.186739207G>A c.[718C>T];[1038+1G>A] - KNG1_000007 A German kindred with a female symptomatic carrier of compound variants c.[718C>T];[1038+1G>A], with abolished expression of HK and LK, and her asymptomatic parents Journal: Adenaeuer 2022 ClinVar-SCV004031440.1 rs377594184 Germline - 0.000009311 - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Adenaeuer 2022 - F - Germany - - - - - 3 Christian Drouet
+?/. 8i c.1038+1G>A r.spl p.? Parent #2 - pathogenic (recessive) g.186456996G>A g.186739207G>A c.[1038+1G>A](;)[1165C>T] - KNG1_000007 compound variants c.[1038+1G>A](;)[1165C>T] abolished expression of both HK and LK The female compound heterozygous proband has been originally described as being prekallikrein (PK) deficient due to low PK activity (7%) Variant c.1038+1G>A introduced in ClinVar as pathogenic by Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Germany PubMed: Barco 2020, Journal: Barco 2020 Journal: Adenaeuer 2022 ClinVar-SCV004031440.1 rs377594184 Germline - 0.000009311 - - - DNA SEQ-NG blood - high molecular weight kininogen deficiency Pat5 PubMed: Barco 2020, Journal: Barco 2020 - F no Switzerland - - - - - 1 Christian Drouet
+?/. 10 c.1136T>A r.(?) p.(Met379Lys) Unknown ACMG pathogenic g.186459321T>A g.186741532T>A - - KNG1_000004 c.1136T>A introduced as Class 4 variant (ACMG classification). p.(Met379Lys) variant changes the N-terminal cleavage site of bradykinin from HK and Lys-bradykinin from LK. This might lead to a functionally active but abnormal bradykinin or Lys-bradykinin in HAE-KNG1, with putative change of the inactivation process by enzymes, e.g. aminopeptidase P, angiotensin-I converting enzyme, and others, possibly resulting in a prolonged half-life time and a higher than normal activity of this mutant peptide ligand. It has been demonstrated that the Met379Lys substitution increases HK and LK susceptibility to cleavage by plasmin, resulting in release of Lys-bradykinin (kallidin). This is the second example of a mutation that could cause HAE independently of plasma kallikrein, and the first described that involves Lys-bradykinin production. Introduced as pathogenic in ClinVar by OMIM; angioedema, hereditary, 6; HAE6 PubMed: Bork 2019 Journal: Bork 2019 Journal: Dickeson 2023 ClinVar-SCV001712268.1 rs752411996 Germline yes 6.860E-7 - - - DNA SEQ-NG - - HAE6 - PubMed: Bork 2019 Journal: Bork 2019 - - no Germany - - - - - 6 Christian Drouet
+/. 10 c.1136T>A r.(?) p.(Met379Lys) Unknown ACMG pathogenic g.186459321T>A g.186741532T>A - - KNG1_000004 This variant (class 4 ACMG) changes the N-terminal cleavage site of bradykinin from both high molecular weight (HMWK) and low molecular weight (LMWK) kininogens.The patient's kininogen immunoblot shows a majority of uncleaved kininogen, with a molecular weight of 120 KDa, and a minority of cleaved kininogen at 45 KDa. Introduced in ClinVar as a pathogenic variant by OMIM; ascribed to hereditary angioedema type 6, HAE6 Journal: Hardy 2023 ClinVar-SCV001712268 rs752411996 Germline yes 6.860E-7 - - - DNA SEQ blood - HAE6 - - - F - France - - - - - 1 Christian Drouet
?/. 10 c.1143G>C r.(?) p.(Arg381Ser) Unknown - VUS g.186459328G>C g.186741539G>C - - KNG1_000029 no family data, considered VUS in line with ACMG criterion PM2 PubMed: Gao 2025, Journal: Gao 2025 - rs759225480 Germline/De novo (untested) - - - - - DNA SEQ-NG - - HAE6 - PubMed: Gao 2025, Journal: Gao 2025 A single male individual in a Chinese family M no China - - - - - 1 Christian Drouet
+?/. 10 c.1165C>T r.(?) p.(Arg389*) Parent #1 - pathogenic (recessive) g.186459350C>T g.186741561C>T c.[1038+1G>A];[1165C>T] - KNG1_000006 compound variant c.[1038+1G>A](;)[1165C>T] c.1165C>T has been introduced as pathogenic in ClinVar by University Medical Center Mainz Germany PubMed: Barco 2020, Journal: Barco 2020 Journal: Adenaeuer 2022 ClinVar-VCV001803726.1 rs752411996 Germline - 0.000006211 - - - DNA SEQ-NG blood - high molecular weight kininogen deficiency Pat5 PubMed: Barco 2020, Journal: Barco 2020 - F no Switzerland - - - - - 1 Christian Drouet
+/. 10 c.1165C>T r.(?) p.(Arg389*) Parent #2 - pathogenic (recessive) g.186459350C>T g.186741561C>T c.[488delG];[1165C>T] - KNG1_000006 Compound c.[488delG];[1165C>T] variants abolish expression of Hk and LK and function of HK c.1165C>T has been introduced as pathogenic in ClinVar by University Medical Center Mainz Germany Journal: Jeung 2020 Journal: Adenaeuer 2022 ClinVar-VCV001803726.1 rs752411996 Germline - 0.000006211 - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Jeung 2020 - M - Korea - - - - - 1 Christian Drouet
+/. 10 c.1165C>T r.(?) p.(Arg389*) Parent #2 ACMG pathogenic (recessive) g.186459350C>T g.186741561C>T c.[618T>G](;)[1165C>T] - KNG1_000006 Compound heterozygous female carrier both c.618T>G and c.1165C>T. c.618T>G variant disrupts the disulfide bond between Cys206 and Cys218; c.1165C>T is a non-sense variant with truncation of the D5 domain of the protein. Journal: Lv 2025 - - Germline - - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Lv 2025 Single family with a compound heterozygous affected individual F no China - - - - - 1 Christian Drouet
+/. 10 c.1216dup r.(?) p.(His406Profs*10) Both (homozygous) - pathogenic (recessive) g.186459401dup g.186741612dup c.[1216dup];[1216dup] - KNG1_000014 A family with 1 homozygous symptomatic proband and 5 heterozygous asymptomatic carriers Journal: Shigekiyo 2007 Journal: Adenaeuer 2022 ClinVar-VCV000000575.1 rs797044430 Germline - - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Shigekiyo 2007 - F yes Japan - - - - - 6 Christian Drouet
-?/. - c.1311A>C r.(?) p.(Arg437Ser) Unknown - likely benign g.186459496A>C - KNG1(NM_001102416.3):c.1311A>C (p.R437S) - KNG1_000017 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. 10 c.1404G>C r.(1404G>C) p.(Gln468His) Unknown ACMG pathogenic g.186459589G>C g.186741800G>C - - KNG1_000026 - Journal: Chen 2025 - rs377185225 Germline/De novo (untested) yes - - - - DNA SEQ - - HAE6 - Journal: Chen 2025 Single individual; no relevant family history. Lanadelumab did not significantly improve the frequency and severity of HAE attacks. F no China - - - - - 1 Christian Drouet
+/. 10 c.1456C>T r.(?) p.(Gln486*) Both (homozygous) - pathogenic (recessive) g.186459641C>T g.186741852C>T c.[1456C>T];[1456C>T] - KNG1_000015 Male homozygous proband and his two homozygous sisters are presenting with a prolonged aPTT and a decreased HK expression Journal: Yang 2020 Journal: Adenaeuer 2022 - - Germline yes - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Yang 2020 - M yes China - - - - - 7 Christian Drouet
+/. 10 c.1493del r.(?) p.(Lys498Serfs*54) Both (homozygous) - pathogenic g.186459678del g.186741889del c.[1493del];[1493del] - KNG1_000016 Homozygous c.[1493del];[1493del] variants abolish HK expression. The KNG1 gene was present in the proband to direct the expression of LK of apparent normal size. Heterozygous carriers exhibit reduced antigenic HK. Truncation or frameshift at or before position 480 of the mature HK prevents biosynthesis, processing, and/or HK secretion Journal: Krijanovski 2003 Journal: Adenaeuer 2022 ClinVar-VCV000000573.1 rs797044429 Germline - - - - - DNA SEQ blood - high molecular weight kininogen deficiency - Journal: Krijanovski 2003 Proband homozygous carrier presenting with a markedly prolonged APTT with a normal prothrombin time, thrombin time, and clottable fibrinogen. No antigenic HK detected M yes France - - - - - 4 Christian Drouet
?/. - c.1609_1610del r.(?) p.(Gln537Aspfs*25) Unknown - VUS g.186459794_186459795del - KNG1(NM_001102416.3):c.1609_1610del (p.(Gln537Aspfs*25)) - KNG1_000025 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1643T>C r.(?) p.(Ile548Thr) Unknown - likely benign g.186459828T>C - KNG1(NM_001102416.2):c.1643T>C (p.(Ile548Thr)), KNG1(NM_001102416.3):c.1643T>C (p.I548T) - KNG1_000018 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.1643T>C r.(?) p.(Ile548Thr) Unknown - VUS g.186459828T>C - KNG1(NM_001102416.2):c.1643T>C (p.(Ile548Thr)), KNG1(NM_001102416.3):c.1643T>C (p.I548T) - KNG1_000018 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. 10 c.1690C>T r.(?) p.(Gln564*) Unknown ACMG likely pathogenic g.186459875C>T g.186742086C>T - - KNG1_000028 no family data, considered likely pathogenic according to ACMG criteria PVS1+PM2 PubMed: Gao 2025, Journal: Gao 2025 - rs768876869 Germline/De novo (untested) - - - - - DNA SEQ-NG - - HAE6 - PubMed: Gao 2025, Journal: Gao 2025 A single affected individual in a Chinese family M no China - - - - - 1 Christian Drouet
+/. 10 c.1720C>G r.(?) p.(Pro574Ala) Paternal (confirmed) ACMG pathogenic (recessive) g.186459905C>G g.186742116C>G - - KNG1_000005 Incomplete penetrance: 1 family, 2 patients had recurrent attacks, also heterozygous for a ACE gene c.1459C>T;p.(Arg487Cys) variant, a third patient, had only one attack during his lifetime and did not carry the ACE variant. Introduced as pathogenic in ClinVar; Angioedema, Hereditary, 6; HAE6 PubMed: Loules 2020 Journal: Loules 2020 ClinVar-SCV001712269.1 rs1369253342 Germline yes 0.000003181 - - - DNA SEQ-NG-IT - - HAE6 family PubMed: Loules 2020, Journal: Loules 2020 3-generation family, 4 carriers (4 males), 3 affected individuals The son of the proband had only one attack during his lifetime, he is carrier of KNG1 c.1720C>G variant, but not of the ACE c.1459C>T variant. M - Italy - - - - - 3 Christian Drouet
+?/. 10 c.1742T>C r.(?) p.(Ile581Thr) Unknown - association g.186459927T>C g.186742138T>C - - KNG1_000021 SNP associated with with a shortening of the activated partial thromboplastin time and increased susceptibility to venous thrombosis Journal: Houlihan 2010 Journal: Morange 2011 Journal: Li 2023 - rs710446 Germline - 0.416246 - - - DNA SEQ - - ? - Journal: Houlihan 2010 Journal: Morange 2011 Journal: Li 2023 - - - - - - - - - 1 Christian Drouet
?/. - c.1744C>T r.(?) p.(Gln582*) Unknown - VUS g.186459929C>T - KNG1(NM_001102416.3):c.1744C>T (p.Q582*) - KNG1_000022 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
./. - c.*1404C>T r.(=) p.(=) Both (homozygous) - pathogenic g.186461524C>T g.186743735C>T - - KNG1_000001 association variant/phenotype uncertain PubMed: DDDS 2015, Journal: DDDS 2015 - - Germline - - - - - DNA SEQ, SEQ-NG-I - - ? - PubMed: DDDS 2015, Journal: DDDS 2015 proband - - United Kingdom (Great Britain) - - - - - 1 Johan den Dunnen
./. - c.*1404C>T r.(=) p.(=) Both (homozygous) - pathogenic g.186461524C>T g.186743735C>T - - KNG1_000001 association variant/phenotype uncertain PubMed: DDDS 2015, Journal: DDDS 2015 - - Germline - - - - - DNA SEQ, SEQ-NG-I - - ? - PubMed: DDDS 2015, Journal: DDDS 2015 uninherited diplotypes - - United Kingdom (Great Britain) - - - - - 1 Johan den Dunnen
./. - c.*1404C>T r.(=) p.(=) Both (homozygous) - pathogenic g.186461524C>T g.186743735C>T - - KNG1_000001 association variant/phenotype uncertain PubMed: DDDS 2015, Journal: DDDS 2015 - - Germline - - - - - DNA SEQ, SEQ-NG-I - - ? - PubMed: DDDS 2015, Journal: DDDS 2015 uninherited diplotypes - - United Kingdom (Great Britain) - - - - - 1 Johan den Dunnen
-?/. - c.*1404C>T r.(?) p.(=) Unknown - benign g.186461524C>T g.186743735C>T NM_000893.4:c.1234C>T - KNG1_000001 The stop variant c.*1404C>T identified by Mathey 2022 is located in exon 11, and downstream of both the bradykinin sequence and its cleavage sites. Exon 11 of KNG1 encodes the unique light chain of LK, whose exact function has yet to be determined. The consequences of the stop variant p.(Arg412Ter) are unclear. Additionally, the variant c.*1404C>T has been shown as a risk allele that increases the stability of KNG1 mRNA, leading to increased susceptibility to HBV infection. Considered benign by Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, Cambridge MA Journal: Mathey 2022 Journal: Zhang 2023 ClinVar-VCV000403021.3 rs76438938 Germline - 0.03019 (gnomAD) - - - DNA SEQ-NG-I - - HAE - - - - - - - - - - - 1 Christian Drouet
Legend   How to query  

Screenscraping/webscraping (downloading large amounts of data using scripts) is strictly prohibited.
Use our APIs to retrieve data.
  Powered by LOVD v.3.0 Build 30b
LOVD software ©2004-2024 Leiden University Medical Center
Database contents © by their respective submitters and curators
 There are currently no updates.