HSD11B2

hydroxysteroid 11-beta dehydrogenase 2, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 16:67430652-67437553

Links

ENSG00000176387 ∙ NCBI:3291 ∙ OMIM:614232 ∙ HGNC:5209 ∙ Uniprot:P80365 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• apparent mineralocorticoid excess (Strong), mode of inheritance: AR
• apparent mineralocorticoid excess (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cortisol 11-beta-ketoreductase deficiency	AR	Renal	There is a broad range of severity, including potentially lethal early chidlhood disease, and medical treatment (eg, with spironolactone) can be beneficial	Endocrine; Renal	870517; 1740492; 3460996; 3164727; 8370690; 7670488; 9683587; 9707624; 10536001; 10523339; 17314322; 19909806

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD11B2 gene.

• Apparent_mineralocorticoid_excess (88 variants)
• not_provided (78 variants)
• Inborn_genetic_diseases (41 variants)
• not_specified (7 variants)
• HSD11B2-related_disorder (4 variants)
• Apparent_mineralocorticoid_excess,_mild (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD11B2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000196.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	26	3	32
missense	5	7	96	7	1	116
nonsense						0
start loss						0
frameshift	5	2	1			8
splice donor/acceptor (+/-2bp)		2				2
Total	10	11	100	33	4

Highest pathogenic variant AF is 0.0000123933

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD11B2	protein_coding	protein_coding	ENST00000326152	5	6902

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.118	0.859	125723	0	9	125732	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	162	203	0.798	0.0000146	2520
Missense in Polyphen		43	72.565	0.59258		1024
Synonymous	-0.0639	89	88.2	1.01	0.00000620	929
Loss of Function	1.95	3	9.47	0.317	4.14e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.0000999	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000445	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the conversion of cortisol to the inactive metabolite cortisone. Modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Steroidogenesis;Apparent mineralocorticoid excess syndrome;3-Beta-Hydroxysteroid Dehydrogenase Deficiency;21-hydroxylase deficiency (CYP21);Corticosterone methyl oxidase I deficiency (CMO I);Corticosterone methyl oxidase II deficiency - CMO II;Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency;Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency;Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH;17-alpha-hydroxylase deficiency (CYP17);11-beta-hydroxylase deficiency (CYP11B1);Glucocorticoid and Mineralcorticoid Metabolism;Prostaglandin Synthesis and Regulation;Metabolism of lipids;Androgen and estrogen biosynthesis and metabolism;Metabolism;Metabolism of steroid hormones;Metabolism of steroids;C21-steroid hormone biosynthesis and metabolism;Glucocorticoid biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.644

Intolerance Scores

• loftool: 0.130
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.25

Haploinsufficiency Scores

• pHI: 0.726
• hipred: Y
• hipred_score: 0.713
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hsd11b2
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; neoplasm; digestive/alimentary phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: response to hypoxia;regulation of blood volume by renal aldosterone;glucocorticoid biosynthetic process;female pregnancy;response to food;response to insulin;response to drug;response to glucocorticoid;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane
• Molecular function: 11-beta-hydroxysteroid dehydrogenase [NAD(P)] activity;steroid binding;NAD binding