Neonatal cholestasis

Gene: HNF1B

Green List (high evidence)

HNF1B (HNF1 homeobox B)
EnsemblGeneIds (GRCh38): ENSG00000275410
EnsemblGeneIds (GRCh37): ENSG00000108753
OMIM: 189907, Gene2Phenotype
HNF1B is in 22 panels

5 reviews

Anna de Burca (Genomics England Curator)

Comment on mode of inheritance: There are no reports of biallelic variants in this gene in patients with cholestasis.
Created: 25 Jul 2018, 11 a.m.
Comment on list classification: Although this gene is not associated with cholestasis in OMIM or Gene2phenotype, 3 unrelated cases of cholestasis have been reported with SNVs in HNF1B (note HNF1B is within the common 17q12 microdeletion syndrome region, and some cases cited in 25741167 are associated with deletions rather than SNVs).
Created: 25 Jul 2018, 10:59 a.m.

Jane Hartley (Birmingham Women and Children's Hospital)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cholestasis; renal cysts; diabetes; ciliopathy

Rachel Jones (GSTT)

Green List (high evidence)

PMID: 25741167 provides a review of the evidence of the role of HNF1B in neonatal and adult onset jaundice and cholestasis, in addition to the more widely known renal cysts and diabetes phenotype.

Has been seen in at least 7 unrelated patients with cholestasis arising at a wide range of ages. One child reported with non-hepatic biliary atresia as well as others with a paucity of intrahepatic bile ducts and some patients (later onset cholestasis) with what they designate a ciliopathy of cholangiocytes.

Mouse model of HNF1B demonstrates HNF1B important in development of biliary system, and knockouts have severe neonatal cholestasis. PMID: 11934849

Not currently listed as a phenotype of HNF1B in OMIM.
Created: 11 Jun 2018, 9:46 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

Thalia Antoniadi (West Midlands Regional Genetics Laboratory)

Red List (low evidence)

This is a diabetes gene; we have not included it in our cholestasis panel becuase it doesnt have an OMIM entry associated to cholestasis or liver abnomral function.
Created: 4 Jun 2018, 11:33 a.m.

Phenotypes
diabetes mellitus; renal cysts and diabetes

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Promoted to green, as there are more than 3 families reported with heterozygous variants in this gene for Renal cysts and diabetes syndrome.
Created: 22 May 2018, 2:10 p.m.

History Filter Activity

3 Sep 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been subjected to extensive internal and external review.

25 Jul 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: HNF1B were set to Cholestasis; neonatal and adult onset jaundice and cholestasis

25 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Anna de Burca (Genomics England Curator)

Gene: hnf1b has been classified as Green List (High Evidence).

25 Jul 2018, Gel status: 3

Set mode of inheritance

Anna de Burca (Genomics England Curator)

Mode of inheritance for gene: HNF1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

25 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Anna de Burca (Genomics England Curator)

Gene: hnf1b has been classified as Green List (High Evidence).

25 Jul 2018, Gel status: 4

Set Phenotypes

Anna de Burca (Genomics England Curator)

Phenotypes for gene: HNF1B were set to Cholestasis

25 Jul 2018, Gel status: 4

Set publications

Anna de Burca (Genomics England Curator)

Publications for gene: HNF1B were set to 25741167; 9398836; 10484768; 10720943; 12161522; 11562418; 11317673; 11085914; 15001636; 17307554; 22706971

25 Jul 2018, Gel status: 4

Set publications

Anna de Burca (Genomics England Curator)

Publications for gene: HNF1B were set to 25741167; 9398836; 10484768; 10720943; 12161522; 11562418; 11317673; 11085914; 15001636; 17307554

21 Jun 2018, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Victorian Clinical Genetics Services was added to HNF1B. Panel: Cholestasis

22 May 2018, Gel status: 3

Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for HNF1B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

22 May 2018, Gel status: 3

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

22 May 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HNF1B were set to 25741167; 9398836; 10484768; 10720943; 12161522; 11562418; 11317673; 11085914

22 May 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HNF1B were set to 25741167; 9398836; 10484768; 10720943; 12161522; 11562418; 11317673

22 May 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HNF1B were set to 25741167; 9398836; 10484768; 10720943; 12161522

22 May 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HNF1B were set to 25741167; 9398836; 10484768; 10720943

22 May 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HNF1B were set to 25741167; 9398836; 10484768

22 May 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HNF1B were set to 25741167; 9398836

22 May 2018, Gel status: 1

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for HNF1B were set to Renal cysts and diabetes syndrome 137920

22 May 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HNF1B were set to 25741167

18 May 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

HNF1B was added to Cholestasis panel. Sources: Emory Genetics Laboratory

18 May 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

HNF1B was created by Ellen McDonagh