HSD11B1

protein-coding

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

Gene summary

The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Mutations in this gene and H6PD (hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)) are the cause of cortisone reductase deficiency. Alternate splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, May 2011]

Previous symbols:

HSD11B
HSD11

MANE transcript

NM_005525.4

Inheritance

AD, AR (Triallelic)

ClinVar variants

P:2U:21B:6

Top phenotype

Cortisone reductase deficiency 2

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr1:209,686,178-209,734,949

External References & Databases

Ensembl (ENSG00000117594)

Transcript & Mutation Effects

hg38 • Region Span ~48.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cortisone reductase deficiency 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0013842

Submitter: PanelApp Australia

cortisone reductase deficiency 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013842

Submitter: Labcorp Genetics (formerly Invitae)

cortisone reductase deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000193

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cortisone reductase deficiency 2AD/AR (Triallelic)

Manifestation: Endocrine

Intervention: General

Rationale: 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

Refs: 3990293; 8923828; 10522997; 12858176; 21325058

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSD11B1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 4

HSD11B1-related disorderTotal: 3

Cortisone reductase deficiency 2Total: 3

Exstrophy-epispadias complexTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005525.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	2 clinvar	5
missense	2 clinvar		20 clinvar	1 clinvar		23
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	2	0	21	4	2	29

Highest pathogenic variant AF is 0.000010534495

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005525.4	RefSeq	NP_005516.1	6	MANE Select
ENST00000367027.5	Ensembl	ENSP00000355994.3	6	MANE Select
NM_001206741.2	RefSeq	NP_001193670.1	6	Standard
NM_181755.3	RefSeq	NP_861420.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

glucocorticoid biosynthetic process
lung development
oxidation-reduction process

Molecular Function

11-beta-hydroxysteroid dehydrogenase [NAD(P)] activity
steroid binding
11-beta-hydroxysteroid dehydrogenase (NADP+) activity

Cellular Component

endoplasmic reticulum membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367028
Coding exons: 6
Length: 48786
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125726
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.959	120	153	0.782	0.00000794	1916
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.632

Intolerance Scores

LoFtool: 0.223
RVIS EVS: -0.43
RVIS percentile EVS: 25.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.971

Gene Damage Prediction

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