SCD5

Summary

SCD5 (stearoyl-CoA desaturase 5, HGNC:21088) is a protein-coding gene on chromosome 4q21.22, encoding Stearoyl-CoA desaturase 5 (Q86SK9). Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates.

Stearoyl-CoA desaturase (SCD; EC 1.14.99.5) is an integral membrane protein of the endoplasmic reticulum that catalyzes the formation of monounsaturated fatty acids from saturated fatty acids. SCD may be a key regulator of energy metabolism with a role in obesity and dislipidemia. Four SCD isoforms, Scd1 through Scd4, have been identified in mouse. In contrast, only 2 SCD isoforms, SCD1 (MIM 604031) and SCD5, have been identified in human. SCD1 shares about 85% amino acid identity with all 4 mouse SCD isoforms, as well as with rat Scd1 and Scd2. In contrast, SCD5 shares limited homology with the rodent SCDs and appears to be unique to primates (Wang et al., 2005 [PubMed 15907797]).

Source: NCBI Gene 79966 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal dominant 79 (Limited, GenCC)
• GWAS associations: 26
• Clinical variants (ClinVar): 55 total — 1 pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes
• MANE Select transcript: NM_001037582

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21088
Approved symbol	SCD5
Name	stearoyl-CoA desaturase 5
Location	4q21.22
Locus type	gene with protein product
Status	Approved
Aliases	ACOD4, FLJ21032, FADS4, HSCD5
Ensembl gene	ENSG00000145284
Ensembl biotype	protein_coding
OMIM	608370
Entrez	79966

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000273908, ENST00000319540

RefSeq mRNA: 2 — MANE Select: NM_001037582 NM_001037582, NM_024906

CCDS: CCDS34024, CCDS3595

Canonical transcript exons

ENST00000319540 — 5 exons

Exon	Start	End
ENSE00000969769	82705283	82705413
ENSE00000969770	82680707	82680912
ENSE00001259847	82636591	82636823
ENSE00001259896	82629539	82631517
ENSE00001384661	82798306	82798796

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5794 / max 743.1998, expressed in 1497 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52880	23.8203	1479
52881	4.3437	956
52871	0.2279	105
52872	0.1085	32
52882	0.0381	23
52879	0.0258	7
52873	0.0149	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	99.72	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.70	gold quality
globus pallidus	UBERON:0001875	99.69	gold quality
medial globus pallidus	UBERON:0002477	99.68	gold quality
substantia nigra pars compacta	UBERON:0001965	99.64	gold quality
subthalamic nucleus	UBERON:0001906	99.61	gold quality
postcentral gyrus	UBERON:0002581	99.60	gold quality
inferior vagus X ganglion	UBERON:0005363	99.56	gold quality
superior vestibular nucleus	UBERON:0007227	99.54	gold quality
cortical plate	UBERON:0005343	99.48	gold quality
parietal lobe	UBERON:0001872	99.46	gold quality
ventral tegmental area	UBERON:0002691	99.31	gold quality
pons	UBERON:0000988	99.20	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.07	gold quality
entorhinal cortex	UBERON:0002728	98.88	gold quality
caudate nucleus	UBERON:0001873	98.86	gold quality
nucleus accumbens	UBERON:0001882	98.86	gold quality
cerebellar vermis	UBERON:0004720	98.81	gold quality
temporal lobe	UBERON:0001871	98.75	gold quality
amygdala	UBERON:0001876	98.68	gold quality
spinal cord	UBERON:0002240	98.63	gold quality
adult organism	UBERON:0007023	98.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.57	gold quality
superior frontal gyrus	UBERON:0002661	98.55	gold quality
anterior cingulate cortex	UBERON:0009835	98.49	gold quality
primary visual cortex	UBERON:0002436	98.46	gold quality
Ammon’s horn	UBERON:0001954	98.43	gold quality
cingulate cortex	UBERON:0003027	98.40	gold quality
prefrontal cortex	UBERON:0000451	98.27	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	1870.91
E-HCAD-35	yes	60.79
E-CURD-119	yes	45.43
E-HCAD-25	yes	22.35
E-GEOD-81608	yes	21.38
E-HCAD-31	yes	18.95
E-MTAB-5061	yes	17.75
E-GEOD-81547	yes	11.70
E-ANND-3	yes	8.28
E-GEOD-93593	yes	6.04
E-ENAD-27	no	11.82

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
EGR2	Unknown

Upstream regulators (CollecTRI, top): EGR2, NFYA, NR1H3, SREBF1

miRNA regulators (miRDB)

44 targeting SCD5, 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-3613-3P	100.00	76.36	7965
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-1288-5P	98.85	67.01	734

Literature-anchored findings (GeneRIF, showing 12)

• The identification and characterization of SCD2, and its relationship to human SCD1 and mouse SCD2, are reported. (PMID:15610069)
• In this paper, we describe for the first time a second SCD isoform in cattle, which appears to be an ortholog of human SCD5 rather than a homolog of bovine SCD1 or any of the described murine SCD isoforms (PMID:17468887)
• Data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation. (PMID:22745828)
• The protective effect of TO901317 was lost after gene silencing of Scd-1/-2, thereby confirming that the protective effect of TO901317 is mediated by Scd-1/-2. (PMID:23867797)
• SCD5 appears to functionally connect tumour cells and the surrounding stroma toward modification of the tumour microenvironment, with consequences on tumour spread and resistance to treatment. (PMID:25802234)
• SCD5 genotype TC, GA, AG, and CG of rs6840, rs1065403, rs3821974, and rs3733230, respectively were higher in control group than hepatocellular carcinoma (HCC). these genotype decreased the risk (rs6840; OR 0.55, rs1065403; OR 0.46, rs3821974; OR 0.56, rs3821974; OR 0.56) of HCC. Our results indicate that polymorphisms in the 3’-UTR of the SCD5 gene may associated with HCC in the Korean male population. (PMID:30168096)
• Whole exome sequencing identifies SCD5 as a novel causative gene for autosomal dominant nonsyndromic deafness. (PMID:31972369)
• Stearoyl-CoA desaturase 5 (SCD5), a Delta-9 fatty acyl desaturase in search of a function. (PMID:33049404)
• SCD5 expression correlates with prognosis and response to neoadjuvant chemotherapy in breast cancer. (PMID:33903614)
• SCD2-mediated cooperative activation of IRF3-IRF9 regulatory circuit controls type I interferon transcriptome in CD4(+) T cells. (PMID:36059459)
• A Single Nucleotide Polymorphism (rs3811792) Affecting Human SCD5 Promoter Activity Is Associated with Diabetes Mellitus. (PMID:36292669)
• Molecular Basis of Unequal Alternative Splicing of Human SCD5 and Its Alteration by Natural Genetic Variations. (PMID:37047490)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Fad2	FBGN0029172
drosophila_melanogaster	CG8630	FBGN0038130
drosophila_melanogaster	Desat2	FBGN0043043
drosophila_melanogaster	Desat1	FBGN0086687
caenorhabditis_elegans		WBGENE00001397
caenorhabditis_elegans		WBGENE00001398
caenorhabditis_elegans		WBGENE00001399

Paralogs (1): SCD (ENSG00000099194)

Protein

Protein identifiers

Stearoyl-CoA desaturase 5 — Q86SK9 (reviewed: Q86SK9)

Alternative names: Acyl-CoA-desaturase 4, HSCD5, Stearoyl-CoA 9-desaturase, Stearoyl-CoA desaturase 2

All UniProt accessions (1): Q86SK9

UniProt curated annotations — full annotation on UniProt →

Function. Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA. Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids. Involved in neuronal cell proliferation and differentiation through down-regulation of EGFR/AKT/MAPK and Wnt signaling pathways.

Subunit / interactions. May self-associate and form homodimers.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Detected in fetal brain, and at lower levels in fetal kidney. Detected in adult brain and pancreas, and at lower levels in kidney and lung. Expressed in spiral ganglion cells and the organ of Corti of fetal cochlea.

Disease relevance. Deafness, autosomal dominant, 79 (DFNA79) [MIM:619086] A form of non-syndromic, progressive sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA79 affected females appear to have milder hearing loss than males. The disease may be caused by variants affecting the gene represented in this entry.

Cofactor. Expected to bind 2 Fe(2+) ions per subunit.

Domain organisation. The histidine box domains are involved in binding the catalytic metal ions.

Miscellaneous. This protein has no ortholog in rodents.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q86SK9-1	1	yes
Q86SK9-2	2

RefSeq proteins (2): NP_001032671, NP_079182 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001522	FADS-1_CS	Conserved_site
IPR005804	FA_desaturase_dom	Domain
IPR015876	Acyl-CoA_DS	Family

Pfam: PF00487

Enzyme classification (BRENDA):

• EC 1.14.19.1 — stearoyl-CoA 9-desaturase (BRENDA: 38 organisms, 111 substrates, 740 inhibitors, 12 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
STEAROYL-COA	0.0033–0.0566	4
NADH	0.003–0.089	2
NADPH	0.038–0.8	2
FAD	0.001	1
FMN	0.0025	1
N-HYDROXY-BENZENECARBOXIMIDAMIDE	—	0
STEAROYL-ACYL-CARRIER PROTEIN	—	0

Catalyzed reactions (Rhea), 2 shown:

• octadecanoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (9Z)-octadecenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:19721)
• hexadecanoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (9Z)-hexadecenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:36931)

UniProt features (33 total): binding site 16, topological domain 5, transmembrane region 4, short sequence motif 3, sequence conflict 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SK9-F1	89.99	0.84

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 (16): 49; 94; 99; 122; 129; 130; 131; 134; 135; 162; 163; 236 …

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-556833	Metabolism of lipids
R-HSA-74160	Gene expression (Transcription)
R-HSA-8978868	Fatty acid metabolism
R-HSA-9675108	Nervous system development
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 128 (showing top): GCM_MAP4K4, BENPORATH_ES_WITH_H3K27ME3, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOZGIT_ESR1_TARGETS_DN, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, KEGG_PPAR_SIGNALING_PATHWAY, GOBP_FATTY_ACID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (4): unsaturated fatty acid biosynthetic process (GO:0006636), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633)

GO Molecular Function (7): stearoyl-CoA 9-desaturase activity (GO:0004768), iron ion binding (GO:0005506), oxidoreductase activity (GO:0016491), palmitoyl-CoA 9-desaturase activity (GO:0032896), acyl-CoA desaturase activity (GO:0016215), 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 (GO:0016717), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Fatty acid metabolism	1
Nervous system development	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Gene expression (Transcription)	1
Metabolism	1
Metabolism of lipids	1
Developmental Biology	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acyl-CoA desaturase activity	2
fatty acid biosynthetic process	1
unsaturated fatty acid metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
transition metal ion binding	1
catalytic activity	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	1
cation binding	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

1648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCD5	ITIH4	Q14624	997
SCD5	GPAM	Q9HCL2	859
SCD5	CD4	P01730	804
SCD5	ERVW-1	Q9UQF0	778
SCD5	CCR5	P51681	727
SCD5	PCK1	P35558	675
SCD5	ELOVL6	Q9H5J4	661
SCD5	FASN	P49327	627
SCD5	ELOVL5	Q9NYP7	604
SCD5	G6PC1	P35575	601
SCD5	NR1H3	Q13133	596
SCD5	FADS2	O95864	587
SCD5	SREBF1	P36956	585
SCD5	ENPEP	Q07075	575
SCD5	FADS1	O60427	550

IntAct

32 interactions, top by confidence:

A	B	Type	Score
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
SCD5	UBE3B	psi-mi:“MI:0915”(physical association)	0.400
	TSPO	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GP9	ESYT2	psi-mi:“MI:0914”(association)	0.350
CHRNA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC22A9	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ATP2A3	UBXN8	psi-mi:“MI:0914”(association)	0.350
VSIG4	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
MPC2	TMBIM6	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC19A2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A14	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A8	CEBPZOS	psi-mi:“MI:0914”(association)	0.350
SLC6A11	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC7A3	ILVBL	psi-mi:“MI:0914”(association)	0.350
	ILVBL	psi-mi:“MI:0914”(association)	0.350
gE	TBC1D8	psi-mi:“MI:0914”(association)	0.350
ATF3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CASP3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CTNNA1	MYO1G	psi-mi:“MI:0914”(association)	0.350
FOS	TMEM223	psi-mi:“MI:0914”(association)	0.350
GATA2	C11orf98	psi-mi:“MI:0914”(association)	0.350
CEBPA	HAX1	psi-mi:“MI:0914”(association)	0.350
TCTN3	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270
TCTN2	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (77): SCD5 (Affinity Capture-MS), SCD5 (Co-fractionation), SCD5 (Co-fractionation), SCD5 (Proximity Label-MS), SCD5 (Proximity Label-MS), SCD5 (Affinity Capture-MS), SCD5 (Proximity Label-MS), SCD5 (Two-hybrid), SCD5 (Proximity Label-MS), SCD5 (Proximity Label-MS), SCD5 (Proximity Label-MS), SCD5 (Proximity Label-MS), SCD5 (Proximity Label-MS), SCD5 (Proximity Label-MS), SCD5 (Proximity Label-MS)

ESM2 similar proteins: A0A0C5PRW9, A0A0C5Q309, A4FV48, A4IFP3, A4UVI1, A8MWK0, A9SIZ6, B2KKL4, B7SB91, B8R1K0, D8X2C5, G5ED44, G5EG11, G5EGN2, O04353, O44390, O60427, O74212, O95864, P07308, P13011, P13516, P32291, Q0VAX3, Q23221, Q3EBF7, Q43469, Q4R749, Q5REA7, Q64420, Q6DDK2, Q6P7B9, Q6T707, Q79EF1, Q86SK9, Q8ISS3, Q8K1P9, Q8S3C1, Q92038, Q920L1

Diamond homologs: A0A0C5Q309, B7SB91, B7SB92, G5ED44, G5EGH6, G5EGN2, O00767, O02858, O44390, O62849, O94523, P07308, P0DOW2, P0DOW3, P13011, P13516, P21147, Q12618, Q2KIA4, Q64420, Q6P7B9, Q6T707, Q6US81, Q704E9, Q75PL7, Q79F73, Q86SK9, Q8ISS3, Q92038, Q95MI7, Q99PL7, Q9BH41, Q9FPD5, Q9LMI4, Q9LVZ3, Q9TT94, Q55406, Q949X0, Q9LMI3, Q9LND8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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.

GO biological processes:

GO term	Partners	Fold	FDR
response to xenobiotic stimulus	6	10.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	45
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
984674	NM_001037582.3(SCD5):c.626G>C (p.Trp209Ser)	Pathogenic

SpliceAI

1614 predictions. Top by Δscore:

Variant	Effect	Δscore
4:82636589:A:AC	donor_gain	1.0000
4:82636590:C:CC	donor_gain	1.0000
4:82637356:A:T	acceptor_gain	1.0000
4:82680703:TTACT:T	donor_loss	1.0000
4:82680704:TAC:T	donor_loss	1.0000
4:82680705:A:AC	donor_gain	1.0000
4:82680705:A:C	donor_loss	1.0000
4:82680706:C:A	donor_loss	1.0000
4:82680706:C:CC	donor_gain	1.0000
4:82680706:CT:C	donor_gain	1.0000
4:82680706:CTTT:C	donor_gain	1.0000
4:82680908:TCATT:T	acceptor_gain	1.0000
4:82680909:CATT:C	acceptor_gain	1.0000
4:82680909:CATTC:C	acceptor_gain	1.0000
4:82680910:ATT:A	acceptor_gain	1.0000
4:82680911:TT:T	acceptor_gain	1.0000
4:82680913:C:CC	acceptor_gain	1.0000
4:82680913:CTGC:C	acceptor_loss	1.0000
4:82705277:CCTCA:C	donor_loss	1.0000
4:82705278:CTCA:C	donor_loss	1.0000
4:82705279:TCAC:T	donor_loss	1.0000
4:82705280:CAC:C	donor_loss	1.0000
4:82705281:A:C	donor_loss	1.0000
4:82705409:GTAGG:G	acceptor_gain	1.0000
4:82705410:TAGG:T	acceptor_gain	1.0000
4:82705411:AGG:A	acceptor_gain	1.0000
4:82705412:GG:G	acceptor_gain	1.0000
4:82705413:GCTG:G	acceptor_loss	1.0000
4:82705414:C:CC	acceptor_gain	1.0000
4:82705414:CTGCA:C	acceptor_loss	1.0000

AlphaMissense

2169 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:82631501:A:C	N273K	0.997
4:82631501:A:T	N273K	0.997
4:82680804:A:G	W158R	0.997
4:82680804:A:T	W158R	0.997
4:82680873:G:C	H135D	0.997
4:82680885:G:C	H131D	0.996
4:82680897:A:G	W127R	0.996
4:82680897:A:T	W127R	0.996
4:82705357:A:G	W97R	0.996
4:82705357:A:T	W97R	0.996
4:82680722:A:T	V185D	0.995
4:82680817:G:C	F153L	0.995
4:82680817:G:T	F153L	0.995
4:82680819:A:G	F153L	0.995
4:82680881:C:G	R132P	0.995
4:82636673:G:C	S240R	0.994
4:82636673:G:T	S240R	0.994
4:82636675:T:G	S240R	0.994
4:82680876:G:C	H134D	0.994
4:82705362:C:G	R95P	0.994
4:82705374:G:T	A91D	0.994
4:82631486:A:C	F278L	0.993
4:82631486:A:T	F278L	0.993
4:82631488:A:G	F278L	0.993
4:82631497:G:C	H275D	0.993
4:82680813:G:C	H155D	0.993
4:82680883:G:C	H131Q	0.993
4:82680883:G:T	H131Q	0.993
4:82680895:C:A	W127C	0.993
4:82680895:C:G	W127C	0.993

dbSNP variants (sampled 300 via entrez): RS1000002400 (4:82748053 G>A), RS1000007850 (4:82740761 T>A), RS1000011584 (4:82766651 G>A,T), RS1000020587 (4:82680219 C>G,T), RS10000393 (4:82726037 T>A,C,G), RS1000051218 (4:82716203 C>A), RS1000073536 (4:82667865 A>C), RS1000079153 (4:82728997 A>C), RS1000088496 (4:82641489 G>T), RS1000110758 (4:82754227 G>A,T), RS1000121085 (4:82672987 G>A), RS1000121220 (4:82715987 C>T), RS1000130743 (4:82787061 ATTGT>A), RS1000147608 (4:82710529 G>A,C), RS1000244613 (4:82790045 TC>T)

Disease associations

OMIM: gene MIM:608370 | disease phenotypes: MIM:619086

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal dominant 79	Limited	Unknown

Mondo (1): hearing loss, autosomal dominant 79 (MONDO:0033668)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000408	Progressive sensorineural hearing impairment
HP:0001751	Abnormal vestibular function
HP:0003581	Adult onset

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST004068_67	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	4.000000e-06
GCST004600_150	Eosinophil percentage of white cells	1.000000e-22
GCST004606_118	Eosinophil count	1.000000e-35
GCST004613_132	Sum neutrophil eosinophil counts	5.000000e-10
GCST004614_151	Granulocyte count	3.000000e-10
GCST004617_96	Eosinophil percentage of granulocytes	9.000000e-23
GCST004618_7	White blood cell count (basophil)	4.000000e-09
GCST004623_2	Neutrophil percentage of granulocytes	2.000000e-20
GCST004624_77	Sum eosinophil basophil counts	2.000000e-35
GCST004627_59	Lymphocyte count	7.000000e-20
GCST005973_27	White blood cell count	1.000000e-13
GCST005977_33	Monocyte count	3.000000e-17
GCST006218_53	Erosive tooth wear (severe vs non-severe)	7.000000e-10
GCST006867_33	Type 2 diabetes	5.000000e-10
GCST009379_261	Type 2 diabetes	4.000000e-10
GCST90002379_47	Basophil count	2.000000e-12
GCST90002381_206	Eosinophil count	2.000000e-83
GCST90002382_598	Eosinophil percentage of white cells	6.000000e-44
GCST90002385_252	High light scatter reticulocyte count	7.000000e-12
GCST90002386_581	High light scatter reticulocyte percentage of red cells	1.000000e-13
GCST90002387_93	Immature fraction of reticulocytes	6.000000e-17
GCST90002388_345	Lymphocyte count	2.000000e-61
GCST90002393_131	Monocyte count	1.000000e-71
GCST90002394_58	Monocyte percentage of white cells	1.000000e-11
GCST90002399_377	Neutrophil percentage of white cells	2.000000e-10
GCST90002407_438	White blood cell count	4.000000e-62

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0007986	reticulocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1275210 (SINGLE PROTEIN)

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

ChEMBL bioactivities

146 potent at pChembl≥5 of 242 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.89	Kd	1.275	nM	CHEMBL5653589
8.89	ED50	1.275	nM	CHEMBL5653589
8.40	IC50	4	nM	CHEMBL1950397
8.00	IC50	10	nM	CHEMBL5842076
7.70	IC50	20	nM	CHEMBL6023405
7.52	IC50	30	nM	CHEMBL5911338
7.52	IC50	30	nM	CHEMBL5902146
7.52	IC50	30	nM	CHEMBL5798346
7.50	IC50	32	nM	CHEMBL1950546
7.40	IC50	40	nM	CHEMBL5839703
7.33	IC50	47	nM	CHEMBL5857575
7.30	IC50	50	nM	CHEMBL6025083
7.28	IC50	52	nM	CHEMBL5813475
7.24	IC50	58	nM	CHEMBL5907436
7.16	IC50	70	nM	CHEMBL5078082
7.14	IC50	73	nM	CHEMBL6021739
7.10	IC50	80	nM	CHEMBL1352938
7.10	IC50	80	nM	CHEMBL6048967
7.05	IC50	90	nM	CHEMBL5874619
7.05	IC50	90	nM	CHEMBL5780505
7.05	IC50	90	nM	CHEMBL5973632
7.05	IC50	90	nM	CHEMBL6043767
6.82	IC50	150	nM	CHEMBL5867189
6.80	IC50	160	nM	CHEMBL5743565
6.70	IC50	200	nM	CHEMBL5872462
6.62	IC50	242	nM	CHEMBL1938871
6.56	IC50	276	nM	CHEMBL5821681
6.52	IC50	305	nM	CHEMBL5799086
6.50	IC50	320	nM	CHEMBL6061054
6.49	IC50	327	nM	CHEMBL5926244
6.46	IC50	350	nM	CHEMBL5836676
6.46	IC50	345	nM	CHEMBL6029085
6.41	IC50	386	nM	CHEMBL5976318
6.38	IC50	420	nM	CHEMBL6005795
6.34	IC50	460	nM	CHEMBL5745753
6.32	IC50	480	nM	CHEMBL5893783
6.32	IC50	480	nM	CHEMBL5903438
6.31	IC50	490	nM	CHEMBL5870256
6.26	IC50	550	nM	CHEMBL5859735
6.24	IC50	580	nM	CHEMBL5793785
6.20	IC50	630	nM	CHEMBL6052832
6.20	IC50	629	nM	CHEMBL5883578
6.19	IC50	650	nM	CHEMBL6045405
6.16	IC50	688	nM	CHEMBL5966357
6.16	IC50	696	nM	CHEMBL6029311
6.16	IC50	700	nM	CHEMBL5843630
6.15	IC50	710	nM	CHEMBL5968890
6.15	IC50	710	nM	CHEMBL5910753
6.11	IC50	770	nM	CHEMBL5826518
6.09	IC50	810	nM	CHEMBL5851121

PubChem BioAssay actives

4 with measured affinity, of 24 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149350: Binding affinity to human SCD5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0013	uM
5-[6-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyridazin-3-yl]pyridine-3-carboxylic acid	647138: Inhibition of human SCD5	ic50	0.0040	uM
2-[5-[3-[3-(2-bromo-5-fluorophenoxy)propoxy]-1,2-oxazol-5-yl]tetrazol-2-yl]acetic acid	647863: Inhibition of human SCD5	ic50	0.0320	uM
2-[5-[3-[2-(2-chloro-5-fluorophenyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-1,2-oxazol-5-yl]tetrazol-2-yl]acetic acid	640653: Inhibition of human SCD-5	ic50	0.2420	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	6
trichostatin A	affects cotreatment, decreases expression, affects expression, increases expression	4
sodium arsenite	increases abundance, increases expression, decreases expression	3
Nickel	decreases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
arsenite	increases methylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
ganoderic acid A	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Demecolcine	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1272960	Binding	Inhibition of human SCD5	2-Aryl benzimidazoles: human SCD1-specific stearoyl coenzyme-A desaturase inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2EQ	Abcam HeLa SCD5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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