HSD11B1

hydroxysteroid 11-beta dehydrogenase 1, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 1:209686177-209734949

Previous symbols: [ "HSD11B", "HSD11" ]

Links

ENSG00000117594 ∙ NCBI:3290 ∙ OMIM:600713 ∙ HGNC:5208 ∙ Uniprot:P28845 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cortisone reductase deficiency (Supportive), mode of inheritance: AD
• cortisone reductase deficiency 2 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cortisone reductase deficiency 2	AD/AR (Triallelic)	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine	3990293; 8923828; 10522997; 12858176; 21325058

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD11B1 gene.

• Inborn genetic diseases (6 variants)
• not provided (4 variants)
• Cortisone reductase deficiency 2 (2 variants)
• not specified (1 variants)
• Exstrophy-epispadias complex (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD11B1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			6			6
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding					3	3
Total	0	0	7	1	4

Variants in HSD11B1

This is a list of pathogenic ClinVar variants found in the HSD11B1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-209704971-C-T		not specified	Uncertain significance (Feb 14, 2023)
1-209705839-C-T			Benign (Dec 31, 2019)
1-209705887-G-A		HSD11B1-related disorder	Benign (Dec 16, 2019)
1-209706751-T-C		not specified	Uncertain significance (Nov 06, 2023)
1-209706778-A-T		not specified	Uncertain significance (Feb 17, 2024)
1-209706809-G-C		not specified	Uncertain significance (May 31, 2023)
1-209706871-C-CA		Cortisone reductase deficiency 2	Benign (Jan 23, 2024)
1-209706914-T-G		Cortisone reductase deficiency 2	Benign (-)
1-209707018-T-A		not specified	Uncertain significance (Dec 21, 2023)
1-209707020-C-T		Cortisone reductase deficiency 2	Pathogenic (Mar 08, 2011)
1-209707093-G-A		not specified	Uncertain significance (Aug 08, 2022)
1-209707113-G-A		not specified	Uncertain significance (Jul 20, 2021)
1-209707136-G-A			Uncertain significance (May 05, 2020)
1-209732427-G-A			Benign (Dec 31, 2019)
1-209732479-G-T		Cortisone reductase deficiency 2	Pathogenic (Mar 08, 2011)
1-209732565-G-C		not specified	Uncertain significance (Jun 29, 2023)
1-209734320-A-AT		Exstrophy-epispadias complex	Uncertain significance (-)
1-209734349-C-T		not specified	Uncertain significance (Jun 10, 2022)
1-209734386-G-C		not specified • HSD11B1-related disorder	Benign/Likely benign (Dec 31, 2019)
1-209734487-C-T		not specified	Uncertain significance (Dec 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD11B1	protein_coding	protein_coding	ENST00000367028	6	48786

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.417	0.576	125717	0	9	125726	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.959	120	153	0.782	0.00000794	1916
Missense in Polyphen		31	45.016	0.68864		523
Synonymous	0.0414	55	55.4	0.993	0.00000305	568
Loss of Function	2.26	2	9.51	0.210	4.11e-7	134

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000528
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7- ketocholesterol to 7-beta-hydroxycholesterol (By similarity). {ECO:0000250}.
• Disease: DISEASE: Cortisone reductase deficiency 2 (CORTRD2) [MIM:614662]: An autosomal dominant error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic- pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo- amenorrhea, and infertility in females and premature pseudopuberty in males. {ECO:0000269|PubMed:12858176}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Chemical carcinogenesis - 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;visceral fat deposits and the metabolic syndrome;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: 0.632

Intolerance Scores

• loftool: 0.223
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.381
• hipred: N
• hipred_score: 0.452
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.971

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hsd11b1
• Phenotype: liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype

Gene ontology

• Biological process: glucocorticoid biosynthetic process;lung development;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: 11-beta-hydroxysteroid dehydrogenase [NAD(P)] activity;steroid binding;11-beta-hydroxysteroid dehydrogenase (NADP+) activity