DEGS2

Summary

DEGS2 (delta 4-desaturase, sphingolipid 2, HGNC:20113) is a protein-coding gene on chromosome 14q32.2, encoding Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 (Q6QHC5). Bifunctional enzyme which acts both as a sphingolipid delta(4)-desaturase and a sphingolipid C4-monooxygenase.

This gene encodes a bifunctional enzyme that is involved in the biosynthesis of phytosphingolipids in human skin and in other phytosphingolipid-containing tissues. This enzyme can act as a sphingolipid delta(4)-desaturase, and also as a sphingolipid C4-hydroxylase.

Source: NCBI Gene 123099 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_206918

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20113
Approved symbol	DEGS2
Name	delta 4-desaturase, sphingolipid 2
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	DES2, FADS8
Ensembl gene	ENSG00000168350
Ensembl biotype	protein_coding
OMIM	610862
Entrez	123099

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000305631, ENST00000553834, ENST00000557117

RefSeq mRNA: 1 — MANE Select: NM_206918 NM_206918

CCDS: CCDS9956

Canonical transcript exons

ENST00000305631 — 3 exons

Exon	Start	End
ENSE00003994192	100159506	100159645
ENSE00003994194	100143957	100146907
ENSE00003994199	100148968	100149710

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 95.57.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9212 / max 141.0391, expressed in 340 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144900	5.3518	306
144901	0.5694	234

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	95.57	gold quality
skin of leg	UBERON:0001511	94.52	gold quality
lower esophagus mucosa	UBERON:0035834	94.49	gold quality
skin of abdomen	UBERON:0001416	93.92	gold quality
zone of skin	UBERON:0000014	92.64	gold quality
bronchial epithelial cell	CL:0002328	92.48	gold quality
bronchus	UBERON:0002185	91.71	gold quality
esophagus mucosa	UBERON:0002469	91.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.41	gold quality
mucosa of transverse colon	UBERON:0004991	89.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.93	gold quality
cerebellar cortex	UBERON:0002129	87.89	gold quality
cerebellar hemisphere	UBERON:0002245	87.85	gold quality
cerebellum	UBERON:0002037	87.26	gold quality
nasal cavity epithelium	UBERON:0005384	86.61	silver quality
duodenum	UBERON:0002114	86.58	gold quality
pancreatic ductal cell	CL:0002079	86.09	silver quality
oocyte	CL:0000023	85.04	gold quality
nipple	UBERON:0002030	84.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.77	gold quality
small intestine	UBERON:0002108	83.04	gold quality
esophagus squamous epithelium	UBERON:0006920	82.98	gold quality
vena cava	UBERON:0004087	82.23	gold quality
jejunal mucosa	UBERON:0000399	82.07	gold quality
mammalian vulva	UBERON:0000997	81.64	gold quality
nasal cavity mucosa	UBERON:0001826	81.17	gold quality
body of stomach	UBERON:0001161	81.02	gold quality
penis	UBERON:0000989	80.68	gold quality
cerebellar vermis	UBERON:0004720	80.56	silver quality
kidney epithelium	UBERON:0004819	80.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	16.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting DEGS2, 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-4533	100.00	69.48	2758
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-6736-3P	96.98	65.22	1342

Literature-anchored findings (GeneRIF, showing 4)

• DES2 was identified and its up-regulation followed during keratinocyte differentiation. (PMID:15063729)
• overexpression of DEGS1 or DEGS2 attenuates the DHC accumulation and increased cell proliferation during hypoxia (PMID:21914808)
• Findings demonstrate that a SNP showing genome-wide association study significant association with cognition in schizophrenia is also associated with regulation of DEGS2 expression, implicating a molecular mechanism for the clinical association. (PMID:25871975)
• Bifunctional DEGS2 has higher hydroxylase activity toward substrates with very-long-chain fatty acids in the production of phytosphingosine ceramides. (PMID:36907437)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	degs2	ENSDARG00000042544
mus_musculus	Degs2	ENSMUSG00000021263
rattus_norvegicus	Degs2	ENSRNOG00000011716
drosophila_melanogaster	ifc	FBGN0001941
caenorhabditis_elegans	ttm-5	WBGENE00013197
caenorhabditis_elegans		WBGENE00017996

Paralogs (1): DEGS1 (ENSG00000143753)

Protein

Protein identifiers

Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 — Q6QHC5 (reviewed: Q6QHC5)

Alternative names: Degenerative spermatocyte homolog 2, Sphingolipid 4-desaturase, Sphingolipid C4-monooxygenase

All UniProt accessions (2): G3V2F9, Q6QHC5

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme which acts both as a sphingolipid delta(4)-desaturase and a sphingolipid C4-monooxygenase.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in skin, intestine and kidney.

Induction. Up-regulated during keratinocyte differentiation. Not expressed at the beginning or day 3 after differentiation, detected on day 6 and increases by day 9.

Pathway. Membrane lipid metabolism; sphingolipid biosynthesis.

Similarity. Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.

RefSeq proteins (1): NP_996801* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005804	FA_desaturase_dom	Domain
IPR011388	DES1/DES2	Family
IPR013866	Sphingolipid_d4-desaturase_N	Domain

Pfam: PF00487, PF08557

Enzyme classification (BRENDA):

• EC 1.14.18.5 — sphingolipid C4-monooxygenase (BRENDA: 11 organisms, 18 substrates, 0 inhibitors, 3 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-ERYTHRO-SPHINGANINE	0.06	1
NADH	0.058	1
NADPH	0.033	1

Catalyzed reactions (Rhea), 4 shown:

• N-octanoylsphinganine + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = N-octanoyl-4-hydroxysphinganine + 2 Fe(III)-[cytochrome b5] + H2O (RHEA:43116)
• an N-acylsphinganine + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = an N-acyl-(4R)-4-hydroxysphinganine + 2 Fe(III)-[cytochrome b5] + H2O (RHEA:46364)
• an N-acylsphinganine + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = an N-acylsphing-4-enine + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:46544)
• a dihydroceramide + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = a phytoceramide + 2 Fe(III)-[cytochrome b5] + H2O (RHEA:55808)

UniProt features (12 total): transmembrane region 3, short sequence motif 3, sequence variant 2, initiator methionine 1, chain 1, region of interest 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6QHC5-F1	96.52	0.96

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis

MSigDB gene sets: 94 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOZGIT_ESR1_TARGETS_DN, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOID_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_DIOL_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_METABOLIC_PROCESS, REACTOME_SPHINGOLIPID_METABOLISM, GOBP_SPHINGOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (4): sphinganine metabolic process (GO:0006667), sphingolipid biosynthetic process (GO:0030148), ceramide biosynthetic process (GO:0046513), lipid metabolic process (GO:0006629)

GO Molecular Function (3): sphingolipid delta-4 desaturase activity (GO:0042284), sphingolipid C4-monooxygenase activity (GO:0102772), oxidoreductase activity (GO:0016491)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Sphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
diol metabolic process	1
sphingoid metabolic process	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
primary metabolic process	1
oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEGS2	RIC3	Q7Z5B4	870
DEGS2	HTR3A	P46098	767
DEGS2	SPTLC1	O15269	717
DEGS2	CERS4	Q9HA82	682
DEGS2	SPTLC3	Q9NUV7	676
DEGS2	SPTLC2	O15270	671
DEGS2	CERS6	Q6ZMG9	639
DEGS2	CHRNA4	P43681	633
DEGS2	CERS5	Q8N5B7	632
DEGS2	UGCG	Q16739	625
DEGS2	KDSR	Q06136	612
DEGS2	CHRNB4	P30926	608
DEGS2	CERS2	Q96G23	582
DEGS2	CERS3	Q8IU89	577
DEGS2	CHRNA3	P32297	570

IntAct

0 interactions, top by confidence:

BioGRID (2): DEGS2 (Affinity Capture-MS), DEGS2 (Protein-peptide)

ESM2 similar proteins: A2XX73, A3F5L3, A5PJS2, C8VRV0, O05883, O12947, O18765, O60725, O88455, P18405, P24008, P31214, Q08388, Q0II71, Q28891, Q41131, Q4KLV1, Q4V7R2, Q564G3, Q5PRC0, Q61907, Q66H21, Q68FF9, Q6NV38, Q6QHC5, Q6RS95, Q71KT5, Q7S5W9, Q7SXF1, Q7XSR9, Q7YRH6, Q7ZW02, Q7ZXH1, Q84UB8, Q84UB9, Q84UC0, Q8C025, Q8GZC2, Q8L586, Q8R2F2

Diamond homologs: C4R613, G5EC63, O09005, O15121, O44186, O59715, Q0II71, Q3ZBY7, Q564G3, Q5AJX2, Q5F3C1, Q5RE51, Q5XIF5, Q68FB8, Q6H5U3, Q6QHC5, Q6UQ04, Q8R2F2, Q94515, Q9ZPH4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

583 predictions. Top by Δscore:

Variant	Effect	Δscore
14:100148963:CATA:C	donor_loss	1.0000
14:100148964:ATAC:A	donor_loss	1.0000
14:100148965:TACCA:T	donor_loss	1.0000
14:100148966:A:AC	donor_gain	1.0000
14:100148966:ACC:A	donor_loss	1.0000
14:100148967:C:CC	donor_gain	1.0000
14:100148967:CCAG:C	donor_gain	1.0000
14:100149706:CTTGG:C	acceptor_gain	1.0000
14:100149708:TGG:T	acceptor_gain	1.0000
14:100149710:GCTG:G	acceptor_loss	1.0000
14:100149711:C:CC	acceptor_gain	1.0000
14:100149711:C:T	acceptor_loss	1.0000
14:100148961:CACAT:C	donor_loss	0.9900
14:100148962:ACATA:A	donor_loss	0.9900
14:100148967:CCA:C	donor_gain	0.9900
14:100149707:TTGG:T	acceptor_gain	0.9900
14:100149709:GG:G	acceptor_gain	0.9900
14:100158929:A:C	acceptor_gain	0.9900
14:100159504:AC:A	donor_gain	0.9900
14:100159505:CC:C	donor_gain	0.9900
14:100146905:CACCT:C	acceptor_loss	0.9800
14:100146906:ACCT:A	acceptor_loss	0.9800
14:100146907:CCTG:C	acceptor_loss	0.9800
14:100146908:C:CC	acceptor_gain	0.9800
14:100146908:C:T	acceptor_loss	0.9800
14:100146909:T:G	acceptor_loss	0.9800
14:100148966:AC:A	donor_gain	0.9800
14:100148967:CC:C	donor_gain	0.9800
14:100149714:C:CT	acceptor_gain	0.9800
14:100159504:A:AC	donor_gain	0.9800

AlphaMissense

2084 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:100149003:C:G	D264H	0.996
14:100149399:G:C	H132D	0.996
14:100149402:G:C	H131D	0.996
14:100149421:G:C	F124L	0.996
14:100149421:G:T	F124L	0.996
14:100149423:A:G	F124L	0.996
14:100148999:A:G	F265S	0.995
14:100149002:T:A	D264V	0.995
14:100149002:T:C	D264G	0.995
14:100149005:T:G	H263P	0.995
14:100149006:G:C	H263D	0.995
14:100149062:G:A	S244F	0.995
14:100149400:G:C	H131Q	0.995
14:100149400:G:T	H131Q	0.995
14:100149002:T:G	D264A	0.994
14:100149004:G:C	H263Q	0.994
14:100149004:G:T	H263Q	0.994
14:100149094:G:C	H233Q	0.994
14:100149094:G:T	H233Q	0.994
14:100149411:G:C	H128D	0.994
14:100149454:G:C	N113K	0.994
14:100149454:G:T	N113K	0.994
14:100159520:C:G	R23P	0.994
14:100149007:G:C	H262Q	0.993
14:100149007:G:T	H262Q	0.993
14:100149009:G:C	H262D	0.993
14:100149043:G:C	N250K	0.993
14:100149043:G:T	N250K	0.993
14:100149095:T:A	H233L	0.993
14:100149148:G:C	S215R	0.993

dbSNP variants (sampled 300 via entrez): RS1000060117 (14:100165324 A>G), RS1000061358 (14:100151082 G>C), RS1000171444 (14:100147245 G>A), RS1000275783 (14:100154182 T>C), RS1000435517 (14:100149397 G>A), RS1000609144 (14:100152657 C>T), RS1000618963 (14:100152842 A>G), RS1000624952 (14:100155871 A>C), RS1000673527 (14:100144091 C>T), RS1000698436 (14:100154463 C>T), RS1000701020 (14:100162012 A>G,T), RS1000736408 (14:100159787 T>G), RS1000767414 (14:100165265 A>C), RS1000773323 (14:100162302 C>T), RS1000800995 (14:100164985 T>C)

Disease associations

OMIM: gene MIM:610862 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001104_2	Sudden cardiac arrest	1.000000e-07
GCST010101_12	White matter hyperintensities	6.000000e-13
GCST010726_60	Periventricular white matter hyperintensities	2.000000e-06
GCST011946_43	White matter hyperintensity volume	1.000000e-08
GCST011947_38	White matter hyperintensity volume	3.000000e-08
GCST011949_13	White matter hyperintensity volume (adjusted for hypertension)	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Sphingolipid Δ⁴-desaturase

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Estradiol	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1
Genistein	increases expression	1

Clinical trials (associated diseases)

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