HSD11B1L

Summary

HSD11B1L (hydroxysteroid 11-beta dehydrogenase 1 like, HGNC:30419) is a protein-coding gene on chromosome 19p13.3, encoding Hydroxysteroid 11-beta-dehydrogenase 1-like protein (Q7Z5J1). Unidirectional NADP(+)-dependent cortisol dehydrogenase (in vitro).

This gene is a member of the hydroxysteroid dehydrogenase family. The encoded protein is similar to an enzyme that catalyzes the interconversion of inactive to active glucocorticoids (e.g. cortisone). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 374875 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_198706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30419
Approved symbol	HSD11B1L
Name	hydroxysteroid 11-beta dehydrogenase 1 like
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SCDR10, SDR26C2, HSD1L
Ensembl gene	ENSG00000167733
Ensembl biotype	protein_coding
Entrez	374875

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 23 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000301382, ENST00000339423, ENST00000342970, ENST00000411793, ENST00000422535, ENST00000423665, ENST00000577257, ENST00000577701, ENST00000577917, ENST00000577920, ENST00000578046, ENST00000578167, ENST00000578832, ENST00000579559, ENST00000579562, ENST00000581423, ENST00000581521, ENST00000581773, ENST00000581893, ENST00000582346, ENST00000583928, ENST00000584904, ENST00000616276, ENST00000889039, ENST00000889040, ENST00000889041, ENST00000889042, ENST00000928620, ENST00000928621, ENST00000928622, ENST00000971819

RefSeq mRNA: 10 — MANE Select: NM_198706 NM_001267868, NM_001267869, NM_001267870, NM_001267871, NM_198533, NM_198704, NM_198705, NM_198706, NM_198707, NM_198708

CCDS: CCDS12144, CCDS12145, CCDS12146, CCDS45931, CCDS45932, CCDS58641, CCDS58642, CCDS74266

Canonical transcript exons

ENST00000339423 — 8 exons

Exon	Start	End
ENSE00001371394	5681027	5681271
ENSE00001791973	5684989	5685119
ENSE00002324380	5684819	5684905
ENSE00003476462	5687282	5687375
ENSE00003572447	5686416	5686527
ENSE00003610267	5687753	5688522
ENSE00003636818	5687503	5687668
ENSE00003656530	5686900	5686991

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 96.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7325 / max 54.2742, expressed in 1081 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173415	3.3874	1178
173417	1.2278	514
173419	0.6659	373
173416	0.5008	252
173420	0.2959	136
173418	0.0420	15

Top tissues by expression

249 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
anterior cingulate cortex	UBERON:0009835	96.33	gold quality
right frontal lobe	UBERON:0002810	96.23	gold quality
amygdala	UBERON:0001876	96.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.86	gold quality
prefrontal cortex	UBERON:0000451	95.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.24	gold quality
nucleus accumbens	UBERON:0001882	93.30	gold quality
putamen	UBERON:0001874	93.17	gold quality
hypothalamus	UBERON:0001898	93.12	gold quality
neocortex	UBERON:0001950	92.73	gold quality
frontal cortex	UBERON:0001870	92.45	gold quality
frontal lobe	UBERON:0016525	92.45	gold quality
caudate nucleus	UBERON:0001873	92.35	gold quality
cerebral cortex	UBERON:0000956	91.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.12	gold quality
forebrain	UBERON:0001890	90.76	gold quality
cerebellar hemisphere	UBERON:0002245	90.49	gold quality
cerebellar cortex	UBERON:0002129	90.36	gold quality
brain	UBERON:0000955	90.08	gold quality
temporal lobe	UBERON:0001871	89.23	gold quality
cerebellum	UBERON:0002037	89.04	gold quality
adenohypophysis	UBERON:0002196	88.72	gold quality
Ammon’s horn	UBERON:0001954	88.70	gold quality
left testis	UBERON:0004533	88.35	gold quality
right testis	UBERON:0004534	88.32	gold quality
right uterine tube	UBERON:0001302	88.13	gold quality
cortical plate	UBERON:0005343	88.10	gold quality
pituitary gland	UBERON:0000007	87.90	gold quality
substantia nigra	UBERON:0002038	87.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.21	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting HSD11B1L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-4484	96.35	64.08	382

Literature-anchored findings (GeneRIF, showing 2)

• cloning, purification, and characterization of SCDR10B; highly expressed in brain (especially in hippocampal neurons); up-regulated in lung cancer cell lines and lung cancer tissue (PMID:19436836)
• Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction. (PMID:36980235)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsd11b1la	ENSDARG00000071377
danio_rerio	hsd11b1lb	ENSDARG00000110341
drosophila_melanogaster	CG7601	FBGN0027583
drosophila_melanogaster	CG31546	FBGN0051546
drosophila_melanogaster	CG31548	FBGN0051548
caenorhabditis_elegans		WBGENE00000970
caenorhabditis_elegans		WBGENE00000975
caenorhabditis_elegans		WBGENE00000981
caenorhabditis_elegans		WBGENE00000993
caenorhabditis_elegans		WBGENE00008985
caenorhabditis_elegans		WBGENE00008986
caenorhabditis_elegans		WBGENE00011424
caenorhabditis_elegans		WBGENE00022809
caenorhabditis_elegans		WBGENE00219274

Paralogs (13): RDH8 (ENSG00000080511), DHRS7 (ENSG00000100612), DHRS2 (ENSG00000100867), DHRS7B (ENSG00000109016), HSD11B1 (ENSG00000117594), HSDL2 (ENSG00000119471), DHRS4 (ENSG00000157326), DHRS1 (ENSG00000157379), CBR1 (ENSG00000159228), CBR3 (ENSG00000159231), DHRS7C (ENSG00000184544), DHRS4L2 (ENSG00000187630), DHRS11 (ENSG00000278535)

Protein

Protein identifiers

Hydroxysteroid 11-beta-dehydrogenase 1-like protein — Q7Z5J1 (reviewed: Q7Z5J1)

Alternative names: 11-beta-hydroxysteroid dehydrogenase type 3, Short chain dehydrogenase/reductase family 26C member 2, Short-chain dehydrogenase/reductase 10B

All UniProt accessions (8): A0A087WWR3, Q7Z5J1, J3KRL3, J3KTC8, J3QKQ3, J3QKX1, J3QS77, J3QSE6

UniProt curated annotations — full annotation on UniProt →

Function. Unidirectional NADP(+)-dependent cortisol dehydrogenase (in vitro).

Subcellular location. Secreted.

Tissue specificity. Highly expressed in the brain.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q7Z5J1-1	1	yes
Q7Z5J1-2	2, B
Q7Z5J1-3	3, G
Q7Z5J1-4	4, F
Q7Z5J1-5	5, C
Q7Z5J1-6	6, A
Q7Z5J1-7	7, D
Q7Z5J1-8	8

RefSeq proteins (10): NP_001254797, NP_001254798, NP_001254799, NP_001254800, NP_940935, NP_941993, NP_941994, NP_941995, NP_941996, NP_941997 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR051253	11-beta-HSD	Family

Pfam: PF00106

Catalyzed reactions (Rhea), 1 shown:

• cortisone + NADPH + H(+) = cortisol + NADP(+) (RHEA:68616)

UniProt features (18 total): splice variant 7, binding site 6, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z5J1-F1	71.56	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 178 (proton acceptor)

Ligand- & substrate-binding residues (6): 211–217; 36–62; 87–88; 114–116; 165; 178–182

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, RFX1_02, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, chr19p13, STAT1_02, ZF5_01, DODD_NASOPHARYNGEAL_CARCINOMA_DN, LU_EZH2_TARGETS_UP, STAT1_03, BARX1_TARGET_GENES, DIDO1_TARGET_GENES, FEV_TARGET_GENES, FOXG1_TARGET_GENES, HES4_TARGET_GENES, KAT5_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): oxidoreductase activity (GO:0016491), cortisol dehydrogenase (NADP+) activity (GO:0102196)

GO Cellular Component (2): extracellular region (GO:0005576), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
catalytic activity	1
11-beta-hydroxysteroid dehydrogenase (NADP+) activity	1
nuclear lumen	1

Protein interactions and networks

STRING

2489 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSD11B1L	MICOS13	Q5XKP0	436
HSD11B1L	LONP1	P36776	343
HSD11B1L	CAT	P04040	341
HSD11B1L	CABS1	Q96KC9	328
HSD11B1L	TMEM134	Q9H6X4	326
HSD11B1L	ARRDC5	A6NEK1	310
HSD11B1L	SAFB2	Q14151	306
HSD11B1L	ROGDI	Q9GZN7	306
HSD11B1L	CELF5	Q8N6W0	301
HSD11B1L	HSD17B1	P14061	296
HSD11B1L	HSD11B2	P80365	293
HSD11B1L	BTBD8	Q5XKL5	293
HSD11B1L	SLC33A2	Q96ES6	281
HSD11B1L	TMEM53	Q6P2H8	281
HSD11B1L	HSD3B2	P26439	270

IntAct

3 interactions, top by confidence:

A	B	Type	Score
HSD11B1L	rep	psi-mi:“MI:0915”(physical association)	0.370
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): HSD11B1L (Positive Genetic), HSD11B1L (Affinity Capture-RNA), HSD11B1L (Negative Genetic), HSD11B1L (Two-hybrid), HSD11B1L (Positive Genetic), PARK2 (Two-hybrid), HSD11B1L (Two-hybrid), PARK2 (Affinity Capture-Western), HSD11B1L (Affinity Capture-Western), HSD11B1L (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A2A6C4, A4FUG7, A5PK74, A6H751, F7E727, O43304, O95382, O95398, P0C025, P35523, P48760, P50168, P51657, P54265, P54777, Q05932, Q08CY5, Q09013, Q13938, Q15477, Q16549, Q1L5Z9, Q3U5Q7, Q4KLY6, Q5MFW3, Q5RER0, Q62849, Q63ZY6, Q643R3, Q6NVG1, Q75NR7, Q76MJ5, Q7Z5J1, Q8CJI3, Q8IUH8, Q8N6F8, Q8NFF5, Q8R2S1, Q8WWF5

Diamond homologs: A0A0B4GT47, A0A0B4GU97, A0A0B4HVU2, A0A140FAN3, A0A8I6GJ95, A0AAT9JA24, A7LB59, A7LB60, D3U1D9, E9EHG1, E9Q3D4, F1QWW8, M2WJF1, M2ZIX7, O31680, O32291, P0A0H9, P0A0I0, P0A2C9, P0A2D0, P0AEK2, P0AEK3, P0DKC5, P0DKC6, P0DKC7, P0DX40, P16232, P25145, P28643, P37959, P40397, P43713, P50172, P50941, P51975, P54554, P69935, P69936, P70385, P72220

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

52 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1665 predictions. Top by Δscore:

Variant	Effect	Δscore
19:5686523:GCTGG:G	donor_gain	1.0000
19:5686524:C:G	donor_gain	1.0000
19:5687500:CAG:C	acceptor_loss	1.0000
19:5687501:A:AG	acceptor_gain	1.0000
19:5687502:G:A	acceptor_loss	1.0000
19:5687502:G:GG	acceptor_gain	1.0000
19:5687502:GGCC:G	acceptor_gain	1.0000
19:5687533:A:AG	acceptor_gain	1.0000
19:5687533:ACTC:A	acceptor_gain	1.0000
19:5687536:C:A	acceptor_gain	1.0000
19:5687664:GTCAG:G	donor_gain	1.0000
19:5687665:TCAGG:T	donor_loss	1.0000
19:5687666:CAGGT:C	donor_loss	1.0000
19:5687667:AGGT:A	donor_loss	1.0000
19:5687667:AGGTG:A	donor_loss	1.0000
19:5687668:GG:G	donor_loss	1.0000
19:5687669:G:C	donor_loss	1.0000
19:5687669:G:GA	donor_loss	1.0000
19:5687669:G:GG	donor_gain	1.0000
19:5687670:T:A	donor_loss	1.0000
19:5688295:GCCTT:G	donor_gain	1.0000
19:5688299:T:G	donor_gain	1.0000
19:5681268:GCGG:G	donor_gain	0.9900
19:5681270:GG:G	donor_gain	0.9900
19:5681271:GG:G	donor_gain	0.9900
19:5681272:G:GC	donor_loss	0.9900
19:5684904:AGGT:A	donor_loss	0.9900
19:5684906:G:A	donor_loss	0.9900
19:5684906:G:C	donor_loss	0.9900
19:5684907:T:A	donor_loss	0.9900

AlphaMissense

1797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5687294:A:C	S141R	0.989
19:5687296:C:A	S141R	0.989
19:5687296:C:G	S141R	0.989
19:5687547:T:C	F183L	0.985
19:5687549:T:A	F183L	0.985
19:5687549:T:G	F183L	0.985
19:5686430:C:G	C73W	0.983
19:5685052:C:A	A46D	0.980
19:5685064:C:A	A50E	0.977
19:5687562:T:C	F188L	0.976
19:5687564:C:A	F188L	0.976
19:5687564:C:G	F188L	0.976
19:5687287:C:A	N138K	0.975
19:5687287:C:G	N138K	0.975
19:5686429:G:A	C73Y	0.973
19:5686513:C:A	A101E	0.972
19:5685088:T:A	L58H	0.971
19:5686915:T:A	L111H	0.971
19:5686428:T:C	C73R	0.969
19:5687295:G:T	S141I	0.964
19:5686915:T:C	L111P	0.963
19:5687358:T:A	V162E	0.960
19:5685010:T:A	V32E	0.959
19:5685085:T:A	V57E	0.959
19:5685063:G:C	A50P	0.958
19:5687565:T:C	F189L	0.956
19:5687567:C:A	F189L	0.956
19:5687567:C:G	F189L	0.956
19:5686909:A:T	D109V	0.954
19:5685013:T:C	L33P	0.951

dbSNP variants (sampled 300 via entrez): RS1000284436 (19:5682605 G>A), RS1000335820 (19:5687964 C>A,T), RS1000668176 (19:5686698 C>A,G), RS1000919098 (19:5682248 A>G), RS1001067229 (19:5687819 C>T), RS1001098231 (19:5688025 A>C,G), RS1001427927 (19:5679458 C>A,T), RS1001555579 (19:5681339 C>T), RS1001876063 (19:5679993 G>A,C), RS1001901704 (19:5681078 T>A,C), RS1002071399 (19:5689016 T>C), RS1002340269 (19:5685341 C>A,T), RS1002561713 (19:5685762 G>A), RS1002725502 (19:5684405 A>C), RS1002771968 (19:5680482 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	4
Particulate Matter	affects expression, decreases reaction, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects expression, decreases reaction	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	affects expression, decreases reaction	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Lead	affects expression	1
NADP	affects binding, increases activity	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

11 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery