HSDL1

Summary

HSDL1 (hydroxysteroid dehydrogenase like 1, HGNC:16475) is a protein-coding gene on chromosome 16q24.1, encoding Inactive hydroxysteroid dehydrogenase-like protein 1 (Q3SXM5).

Located in intermediate filament cytoskeleton and mitochondrion.

Source: NCBI Gene 83693 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total — 1 pathogenic
• MANE Select transcript: NM_031463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16475
Approved symbol	HSDL1
Name	hydroxysteroid dehydrogenase like 1
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	SDR12C3
Ensembl gene	ENSG00000103160
Ensembl biotype	protein_coding
OMIM	619067
Entrez	83693

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000219439, ENST00000434463, ENST00000562224, ENST00000564998, ENST00000565275, ENST00000567294, ENST00000568857, ENST00000619773, ENST00000860767, ENST00000860768, ENST00000934215, ENST00000934216, ENST00000950802, ENST00000950803, ENST00000950804, ENST00000950805

RefSeq mRNA: 2 — MANE Select: NM_031463 NM_001146051, NM_031463

CCDS: CCDS10942, CCDS54046

Canonical transcript exons

ENST00000219439 — 6 exons

Exon	Start	End
ENSE00000695373	84129986	84130431
ENSE00000920963	84129548	84129775
ENSE00001174789	84131102	84131327
ENSE00001191075	84135544	84135605
ENSE00002590467	84122141	84124728
ENSE00002619307	84145080	84145177

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7693 / max 69.9433, expressed in 1649 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158336	4.7693	1649

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.14	gold quality
ganglionic eminence	UBERON:0004023	97.34	gold quality
embryo	UBERON:0000922	97.33	gold quality
ventricular zone	UBERON:0003053	95.31	gold quality
adrenal tissue	UBERON:0018303	95.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.10	gold quality
oviduct epithelium	UBERON:0004804	90.49	gold quality
hypothalamus	UBERON:0001898	89.88	gold quality
left lobe of thyroid gland	UBERON:0001120	89.82	gold quality
nucleus accumbens	UBERON:0001882	89.60	gold quality
right lobe of thyroid gland	UBERON:0001119	89.51	gold quality
thyroid gland	UBERON:0002046	89.45	gold quality
prefrontal cortex	UBERON:0000451	88.94	gold quality
anterior cingulate cortex	UBERON:0009835	88.83	gold quality
islet of Langerhans	UBERON:0000006	88.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.60	gold quality
pituitary gland	UBERON:0000007	88.46	gold quality
adenohypophysis	UBERON:0002196	88.45	gold quality
dorsal root ganglion	UBERON:0000044	88.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.30	gold quality
tendon of biceps brachii	UBERON:0008188	88.30	silver quality
right adrenal gland cortex	UBERON:0035827	88.25	gold quality
cerebellar cortex	UBERON:0002129	88.10	gold quality
cerebellar hemisphere	UBERON:0002245	88.05	gold quality
right adrenal gland	UBERON:0001233	88.04	gold quality
buccal mucosa cell	CL:0002336	87.98	silver quality
left adrenal gland	UBERON:0001234	87.84	gold quality
adrenal gland	UBERON:0002369	87.71	gold quality
cerebellum	UBERON:0002037	87.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.77
E-GEOD-124858	no	269.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting HSDL1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929

Literature-anchored findings (GeneRIF, showing 2)

• novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) located on human chromosome 16q24.2 is highly expressed in reproductive tissues [HSDL1] (PMID:12153137)
• characterized the subcellular localization as well as the tissue distribution and performed a screen for putative substrates of HSDL1 enzymes (PMID:19026618)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsdl1	ENSDARG00000041736
mus_musculus	Hsdl1	ENSMUSG00000034189
rattus_norvegicus	Hsdl1	ENSRNOG00000015576
drosophila_melanogaster	CG13284	FBGN0032614
drosophila_melanogaster	CG6012	FBGN0032615
drosophila_melanogaster	CG31809	FBGN0051809
drosophila_melanogaster	CG31810	FBGN0051810
caenorhabditis_elegans		WBGENE00000990

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH16 (ENSG00000139547), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), SDR9C7 (ENSG00000170426), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), WWOX (ENSG00000186153), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

Inactive hydroxysteroid dehydrogenase-like protein 1 — Q3SXM5 (reviewed: Q3SXM5)

Alternative names: Short chain dehydrogenase/reductase family 12C member 3

All UniProt accessions (4): Q3SXM5, H3BNH5, H3BQI7, H3BT52

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with STYXL1.

Subcellular location. Mitochondrion.

Tissue specificity. Highly expressed in testis and ovary. Also detected in thyroid, spinal cord, adrenal gland, heart, placenta, skeletal muscle, small intestine, colon, spleen, prostate and pancreas.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3SXM5-1	1	yes
Q3SXM5-2	2

RefSeq proteins (2): NP_001139523, NP_113651* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR052149	17-beta-HSD3-like	Family

Pfam: PF00106

UniProt features (13 total): binding site 3, sequence conflict 2, sequence variant 2, initiator methionine 1, chain 1, mutagenesis site 1, region of interest 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3SXM5-F1	92.42	0.80

Functional residue map

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

Ligand- & substrate-binding residues (3): 74–80; 125; 222

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
218	restores the oxidoreductase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, RFX1_02, YAMAZAKI_TCEB3_TARGETS_UP, YGCGYRCGC_UNKNOWN, AHR_Q5, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, NRF1_Q6, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_DN, FOXN3_TARGET_GENES, HAND1_TARGET_GENES, NAB2_TARGET_GENES, SKIL_TARGET_GENES, TFEB_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), intermediate filament cytoskeleton (GO:0045111)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cytoskeleton	1

Protein interactions and networks

STRING

2038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSDL1	SPRYD7	Q5W111	472
HSDL1	ABITRAM	Q9NX38	443
HSDL1	SMIM15	Q7Z3B0	418
HSDL1	GINS2	Q9Y248	416
HSDL1	NIPAL3	Q6P499	415
HSDL1	NHERF4	Q86UT5	403
HSDL1	C15orf61	A6NNL5	400
HSDL1	IFFO2	Q5TF58	397
HSDL1	FBXO41	Q8TF61	396
HSDL1	SERAC1	Q96JX3	392
HSDL1	AMZ2	Q86W34	391
HSDL1	NIPAL1	Q6NVV3	389
HSDL1	HSDL2	Q6YN16	389
HSDL1	ZACN	Q401N2	383
HSDL1	SCP2	P22307	381

IntAct

91 interactions, top by confidence:

A	B	Type	Score
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
TSPAN2	TSPAN3	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
EDA2R	ICAM1	psi-mi:“MI:0914”(association)	0.530
PPTC7	UBB	psi-mi:“MI:0914”(association)	0.530
CD63	LGALS8	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
	ESYT2	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
VIPR2	C15orf61	psi-mi:“MI:0914”(association)	0.350
LYPD3	CLASP2	psi-mi:“MI:0914”(association)	0.350
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
FPR2	GPR89A	psi-mi:“MI:0914”(association)	0.350
TRABD	NME2	psi-mi:“MI:0914”(association)	0.350
RNF19B		psi-mi:“MI:0914”(association)	0.350
MGRN1	ATRN	psi-mi:“MI:0914”(association)	0.350
PPTC7	AIFM1	psi-mi:“MI:0914”(association)	0.350
EDA2R	TK1	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140FAN3, A1L1W4, A5PJF6, A5PJJ7, A7LB59, A7LB60, F1QLP1, O16881, P0DKC5, P0DKC6, P0DKC7, P16232, P28845, P50172, P51975, P70385, Q02337, Q02338, Q09851, Q10130, Q29608, Q3SXM5, Q4V8B7, Q5M875, Q5R7K0, Q5XGF7, Q5ZJG8, Q5ZJZ5, Q6AYS8, Q6DCT3, Q6NRV4, Q6P3L6, Q6QA32, Q6QLL4, Q6R0J2, Q7T2D1, Q80XN0, Q80ZF7, Q8BTX9, Q8HZJ8

Diamond homologs: A0A1U8QWA2, A1C6J8, A1DH66, A2QCH3, A3LXZ3, A4QTE3, A5DND6, A5E0R1, A5PJF6, A6RBW9, A6SG70, A6ZLA1, A7F8T1, A7IQF2, A7TMJ2, A8N6B4, A8Q1U2, B0D8R3, B0XSI3, B2B3L4, B2WMJ3, B3LN00, G0RNA2, O16925, O17795, O31767, O54939, O57314, O70503, P0CR34, P0CR35, P14802, P37058, P38286, P41177, P51831, P70385, Q09517, Q0CY11, Q0IH28

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of nucleotides	5	19.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	54
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1076225	NC_000016.9:g.(?84005756)(84164926_?)del	Pathogenic

SpliceAI

1057 predictions. Top by Δscore:

Variant	Effect	Δscore
16:84131121:T:TA	donor_gain	1.0000
16:84130431:CCTAG:C	acceptor_loss	0.9900
16:84130432:C:CC	acceptor_gain	0.9900
16:84130433:T:G	acceptor_loss	0.9900
16:84130437:A:AC	acceptor_gain	0.9900
16:84131101:CCG:C	donor_gain	0.9900
16:84131126:A:AC	donor_gain	0.9900
16:84131127:C:CC	donor_gain	0.9900
16:84131127:CTG:C	donor_gain	0.9900
16:84145074:CGGTA:C	donor_loss	0.9900
16:84145075:GGTAC:G	donor_loss	0.9900
16:84145076:GTAC:G	donor_loss	0.9900
16:84145077:TA:T	donor_loss	0.9900
16:84145079:C:CG	donor_loss	0.9900
16:84124729:C:CC	acceptor_gain	0.9800
16:84130429:CAC:C	acceptor_gain	0.9800
16:84131329:T:A	acceptor_loss	0.9800
16:84135538:TCTTA:T	donor_loss	0.9800
16:84135539:CTTA:C	donor_loss	0.9800
16:84135540:TTAC:T	donor_loss	0.9800
16:84135541:TACCT:T	donor_loss	0.9800
16:84135542:ACCTT:A	donor_loss	0.9800
16:84135543:C:A	donor_loss	0.9800
16:84129542:TCCTA:T	donor_loss	0.9700
16:84129543:CCTAC:C	donor_loss	0.9700
16:84129544:CTACC:C	donor_loss	0.9700
16:84129545:TA:T	donor_loss	0.9700
16:84129546:A:T	donor_loss	0.9700
16:84129547:CCTGA:C	donor_loss	0.9700
16:84131324:CAAC:C	acceptor_gain	0.9700

AlphaMissense

2158 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:84129607:C:G	A279P	0.992
16:84130050:A:T	V201D	0.991
16:84129707:A:C	S245R	0.988
16:84129707:A:T	S245R	0.988
16:84129709:T:G	S245R	0.988
16:84129606:G:T	A279D	0.986
16:84129755:G:C	S229R	0.986
16:84129755:G:T	S229R	0.986
16:84129757:T:G	S229R	0.986
16:84130389:G:T	A88E	0.984
16:84129570:C:T	G291E	0.982
16:84129993:G:T	A220D	0.982
16:84131237:C:G	G29R	0.981
16:84131237:C:T	G29R	0.981
16:84129603:A:T	V280D	0.980
16:84130106:A:C	S182R	0.979
16:84130106:A:T	S182R	0.979
16:84130108:T:G	S182R	0.979
16:84131107:A:T	V72D	0.979
16:84131110:A:T	V71D	0.979
16:84131113:G:T	A70D	0.979
16:84131211:G:C	S37R	0.979
16:84131211:G:T	S37R	0.979
16:84131213:T:G	S37R	0.979
16:84131236:C:T	G29E	0.979
16:84130057:C:G	A199P	0.977
16:84130392:A:G	L87S	0.977
16:84129751:C:G	A231P	0.976
16:84130402:C:G	A84P	0.976
16:84129565:A:G	W293R	0.974

dbSNP variants (sampled 300 via entrez): RS1000028233 (16:84144293 G>C), RS1000122902 (16:84128008 C>T), RS1000203766 (16:84138061 C>G,T), RS1000318181 (16:84132529 C>G,T), RS1000321871 (16:84145881 C>G,T), RS1000367900 (16:84123724 A>C,G), RS1000404368 (16:84128208 G>A), RS1000526907 (16:84129728 A>G), RS1000544994 (16:84141402 A>G), RS1000574127 (16:84138233 T>G), RS1000815246 (16:84136810 G>C), RS1000962732 (16:84129471 T>C), RS1000971704 (16:84125034 CCCA>C), RS1000994173 (16:84141245 T>A), RS1001065837 (16:84132354 T>C)

Disease associations

OMIM: gene MIM:619067 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004097_3	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	3.000000e-06
GCST007393_9	Mitochondrial DNA copy number	5.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007943	response to platinum-based neoadjuvant chemotherapy
EFO:0006312	mitochondrial DNA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Tretinoin	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
potassium perchlorate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
fipronil	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
DEET	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
NADP	increases activity, affects binding	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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