DHRS7C

Summary

DHRS7C (dehydrogenase/reductase 7C, HGNC:32423) is a protein-coding gene on chromosome 17p13.1, encoding Dehydrogenase/reductase SDR family member 7C (A6NNS2). NADH-dependent oxidoreductase which catalyzes the oxidation of all-trans-retinol to all-trans-retinal.

Predicted to enable all-trans-retinol dehydrogenase (NAD+) activity. Predicted to be involved in D-glucose import; intracellular calcium ion homeostasis; and regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum. Predicted to be located in longitudinal sarcoplasmic reticulum and sarcoplasmic reticulum membrane.

Source: NCBI Gene 201140 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_001105571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32423
Approved symbol	DHRS7C
Name	dehydrogenase/reductase 7C
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	SDR32C2
Ensembl gene	ENSG00000184544
Ensembl biotype	protein_coding
OMIM	616161
Entrez	201140

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000330255, ENST00000571134, ENST00000571771

RefSeq mRNA: 2 — MANE Select: NM_001105571 NM_001105571, NM_001220493

CCDS: CCDS56020, CCDS58517

Canonical transcript exons

ENST00000571134 — 6 exons

Exon	Start	End
ENSE00001299396	9772767	9772922
ENSE00001309783	9771438	9771696
ENSE00001316112	9777193	9777285
ENSE00001320148	9781482	9781594
ENSE00002681802	9779825	9780035
ENSE00003907828	9791131	9791592

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 97.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3330 / max 82.3654, expressed in 39 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164498	0.3330	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	97.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.62	gold quality
biceps brachii	UBERON:0001507	97.41	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.30	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.21	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.88	gold quality
quadriceps femoris	UBERON:0001377	96.86	gold quality
right atrium auricular region	UBERON:0006631	96.53	gold quality
cardiac atrium	UBERON:0002081	96.24	gold quality
skeletal muscle tissue	UBERON:0001134	95.48	gold quality
gastrocnemius	UBERON:0001388	93.50	gold quality
apex of heart	UBERON:0002098	93.27	gold quality
myocardium	UBERON:0002349	92.52	gold quality
muscle of leg	UBERON:0001383	91.97	gold quality
deltoid	UBERON:0001476	91.14	gold quality
muscle tissue	UBERON:0002385	90.99	gold quality
left ventricle myocardium	UBERON:0006566	90.21	gold quality
tibialis anterior	UBERON:0001385	87.15	silver quality
body of tongue	UBERON:0011876	86.64	gold quality
heart left ventricle	UBERON:0002084	85.41	gold quality
cardiac ventricle	UBERON:0002082	85.11	gold quality
heart	UBERON:0000948	82.63	gold quality
heart right ventricle	UBERON:0002080	82.31	gold quality
tongue	UBERON:0001723	77.41	gold quality
vena cava	UBERON:0004087	77.30	gold quality
kidney epithelium	UBERON:0004819	69.64	gold quality
superior surface of tongue	UBERON:0007371	67.40	gold quality
gingival epithelium	UBERON:0001949	66.31	gold quality
pharyngeal mucosa	UBERON:0000355	65.67	gold quality
nasal cavity epithelium	UBERON:0005384	63.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.46

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• The expression of DHRS7c, a novel endo/sarcoplasmic reticulum-localized a short chain dehydrogenase/reductase, is inversely correlated with adrenergic stimulation and heart failure development. (PMID:22143674)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhrs7ca	ENSDARG00000039453
danio_rerio	dhrs7cb	ENSDARG00000071877
mus_musculus	Dhrs7c	ENSMUSG00000033044
rattus_norvegicus	Dhrs7c	ENSRNOG00000026548
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), HSD11B1L (ENSG00000167733), DHRS4L2 (ENSG00000187630), DHRS11 (ENSG00000278535)

Protein

Protein identifiers

Dehydrogenase/reductase SDR family member 7C — A6NNS2 (reviewed: A6NNS2)

Alternative names: Sarcoplasmic reticulum protein of 35 kDa, Short-chain dehydrogenase/reductase family 32C member 2

All UniProt accessions (2): A6NNS2, I3NI52

UniProt curated annotations — full annotation on UniProt →

Function. NADH-dependent oxidoreductase which catalyzes the oxidation of all-trans-retinol to all-trans-retinal. Plays a role in the regulation of cardiac and skeletal muscle metabolic functions. Maintains Ca(2+) intracellular homeostasis by repressing Ca(2+) release from the sarcoplasmic reticulum (SR) in myotubes, possibly through local alternations in NAD/NADH or retinol/retinal. Also plays a role in Ca(2+) homeostasis by controlling Ca(2+) overload in the cytosol and the SR in myotubes. Involved in glucose uptake into skeletal muscles and muscle performance by activating PI3K and mTORC2-mediated AKT1 phosphorylation signaling pathways, possibly through the action of its downstream catalytic product all-trans-retinoic acid.

Subcellular location. Sarcoplasmic reticulum membrane.

Domain organisation. The N-terminus region encompasses a short hydrophobic sequence bound to the sarcoplasmic reticulum membrane, whereas the C-terminus catalytic domain faces the myoplasm.

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

Isoforms (2)

UniProt ID	Names	Canonical?
A6NNS2-1	1	yes
A6NNS2-2	2

RefSeq proteins (2): NP_001099041, NP_001207422 (=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
IPR052148	SDR_family_member_7C	Family

Pfam: PF00106

Catalyzed reactions (Rhea), 1 shown:

• all-trans-retinol + NAD(+) = all-trans-retinal + NADH + H(+) (RHEA:21284)

UniProt features (10 total): binding site 5, signal peptide 1, chain 1, active site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NNS2-F1	87.11	0.67

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): 192 (proton acceptor)

Ligand- & substrate-binding residues (5): 47; 49; 192; 196; 227

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (3): intracellular calcium ion homeostasis (GO:0006874), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), obsolete D-glucose import (GO:0046323)

GO Molecular Function (3): all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), oxidoreductase activity (GO:0016491)

GO Cellular Component (5): longitudinal sarcoplasmic reticulum (GO:0014801), sarcoplasmic reticulum membrane (GO:0033017), cytoplasm (GO:0005737), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
sarcoplasmic reticulum	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol	1
alcohol dehydrogenase (NAD+) activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
catalytic activity	1
endoplasmic reticulum membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1
endoplasmic reticulum	1
sarcoplasm	1

Protein interactions and networks

STRING

2973 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHRS7C	SAYSD1	Q9NPB0	649
DHRS7C	AKIP1	Q9NQ31	607
DHRS7C	MCRIP1	C9JLW8	607
DHRS7C	DNAH8	Q96JB1	497
DHRS7C	RCVRN	P35243	434
DHRS7C	VSTM5	A8MXK1	420
DHRS7C	GCKR	Q14397	383
DHRS7C	GLP2R	O95838	379
DHRS7C	DPP4	P27487	374
DHRS7C	GIPR	P48546	369
DHRS7C	PRL	P01236	350
DHRS7C	DNAH5	Q8TE73	349
DHRS7C	TLCD1	Q96CP7	341
DHRS7C	GCG	P01275	336
DHRS7C	STX8	Q9UNK0	332

IntAct

0 interactions, top by confidence:

BioGRID (2): DHRS7C (Synthetic Lethality), DHRS7C (Affinity Capture-MS)

ESM2 similar proteins: A1YER2, A1YFX9, A2T7G9, A6NNS2, B0BN93, B0BNF8, O22718, O35331, O35678, O75911, O77769, O80526, O88876, O95154, P11172, P14755, P15904, P84169, Q06136, Q15738, Q1RMJ5, Q28DS0, Q2KIJ5, Q2QNG7, Q2QZ86, Q3SZM9, Q3T067, Q3ZBE9, Q5E964, Q5I0K3, Q5PPL3, Q5R514, Q5R5C9, Q5RDZ2, Q6AY30, Q6UWP2, Q811X6, Q86WA6, Q8JGT5, Q8K183

Diamond homologs: A0A017SEY2, A0A078ISJ6, A0A0C6DRT7, A0A0U5CNP2, A0A140FAN3, A0A1B7YCL6, A0A1J0HSL5, A0A1U8QWA2, A0A1V0QS34, A0A2H3CZZ2, A0A2H3D905, A0A4P8W851, A0PJE2, A2RVM0, A6NNS2, A7AZH2, B2X050, D3ZGP9, D7UQ42, D7UTD0, E3VWI6, G9FRD7, I1RL15, K2RU68, M2ZIX7, O05730, O06413, O32229, O74959, O86034, P0DKC7, P16152, P16542, P23102, P35320, P41177, P47727, P50199, P50200, P50203

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

917 predictions. Top by Δscore:

Variant	Effect	Δscore
17:9772751:C:A	donor_gain	1.0000
17:9772765:A:AC	donor_gain	1.0000
17:9772766:C:CC	donor_gain	1.0000
17:9772766:CATTT:C	donor_gain	1.0000
17:9772784:T:TA	donor_gain	1.0000
17:9772785:C:A	donor_gain	1.0000
17:9773493:C:CT	acceptor_gain	1.0000
17:9777191:A:AC	donor_gain	1.0000
17:9777192:C:CC	donor_gain	1.0000
17:9777192:CAAGT:C	donor_gain	1.0000
17:9779818:A:AC	donor_gain	1.0000
17:9779819:C:CC	donor_gain	1.0000
17:9779819:CGAGA:C	donor_gain	1.0000
17:9780045:C:CT	acceptor_gain	1.0000
17:9780046:A:T	acceptor_gain	1.0000
17:9791127:TTACC:T	donor_loss	1.0000
17:9791129:A:AC	donor_gain	1.0000
17:9791129:AC:A	donor_gain	1.0000
17:9791129:ACCCT:A	donor_loss	1.0000
17:9791130:C:CC	donor_gain	1.0000
17:9791130:C:G	donor_loss	1.0000
17:9791130:CC:C	donor_gain	1.0000
17:9771692:AAAGA:A	acceptor_gain	0.9900
17:9771693:AAGA:A	acceptor_gain	0.9900
17:9771694:AGA:A	acceptor_gain	0.9900
17:9772750:T:TA	donor_gain	0.9900
17:9772761:TCTCA:T	donor_loss	0.9900
17:9772762:CTCAC:C	donor_loss	0.9900
17:9772763:TCA:T	donor_loss	0.9900
17:9772764:CACAT:C	donor_loss	0.9900

AlphaMissense

2031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:9772913:G:A	S195F	0.991
17:9772916:G:T	A194D	0.991
17:9772913:G:T	S195Y	0.990
17:9779935:A:G	L124P	0.989
17:9791166:A:T	V40E	0.987
17:9771567:C:G	R287P	0.986
17:9772877:C:G	R207P	0.985
17:9772880:A:G	L206P	0.985
17:9772882:G:C	C205W	0.985
17:9781592:A:G	C53R	0.983
17:9791163:A:T	V41E	0.983
17:9772891:G:C	F202L	0.982
17:9772891:G:T	F202L	0.982
17:9772893:A:G	F202L	0.982
17:9772904:G:T	A198E	0.982
17:9779941:T:A	D122V	0.982
17:9772905:C:G	A198P	0.980
17:9777279:A:G	L163P	0.980
17:9772843:G:C	S218R	0.978
17:9772843:G:T	S218R	0.978
17:9772845:T:G	S218R	0.978
17:9781588:G:T	A54D	0.978
17:9781550:A:G	C67R	0.977
17:9781555:A:T	V65E	0.976
17:9771579:G:T	A283D	0.975
17:9779853:A:C	N151K	0.975
17:9779853:A:T	N151K	0.975
17:9779845:C:T	G154D	0.974
17:9772880:A:T	L206H	0.973
17:9777243:A:T	V175E	0.973

dbSNP variants (sampled 300 via entrez): RS1000113368 (17:9778195 T>C), RS1000272721 (17:9772586 G>A), RS1000311905 (17:9783159 T>C), RS1000371908 (17:9789049 G>A), RS1000557956 (17:9784735 T>C), RS1000708587 (17:9790097 A>C), RS1000901299 (17:9783242 C>G,T), RS1000950129 (17:9782683 C>T), RS1000963411 (17:9772548 C>A,T), RS1001037593 (17:9778043 A>G,T), RS1001052990 (17:9784494 CAG>C), RS1001099006 (17:9776905 C>T), RS1001109903 (17:9778400 A>G), RS1001304593 (17:9791272 C>T), RS1001356469 (17:9791600 T>C,G)

Disease associations

OMIM: gene MIM:616161 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	decreases methylation	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Folic Acid	decreases expression	1
NADP	affects binding, increases activity	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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