SCD5

protein-coding

stearoyl-CoA desaturase 5, the group of Fatty acid desaturases|MicroRNA protein coding host genes

Gene summary

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]).[supplied by OMIM, Mar 2008]

Previous symbols:

SCD4

MANE transcript

NM_001037582.3

Inheritance

ClinVar variants

P:1U:45B:5

Top phenotype

Deafness, autosomal dominant 79

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr4:82,629,539-82,798,796

External References & Databases

Ensembl (ENSG00000145284)

Transcript & Mutation Effects

hg38 • Region Span ~169.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss, autosomal dominant 79LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0033668

Submitter: PanelApp Australia

autosomal dominant nonsyndromic hearing lossLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: ClinGen

SCD5 was first reported in relation to autosomal dominant nonsyndromic hearing loss in 2020 (Lu X et al., PMID:31972369). Two missense variants c.626G>C (p.Trp209Ser), c.452T>G (p.Phe151Cys) have been reported in two probands in two publications (PMID: 31972369, 40121402). One family was reported with eight segregations. The mechanism of pathogenicity appears to be dominant negative. The age of onset of HL varied from 20 to 65 years old and the audiometric profiles were highly asymmetric (PMID: 31972369). This gene-disease relationship is also supported by experimental evidence. SCD5 is primarily expressed in the human fetal and adult brain (GTEx Portal), and protein expression was also observed within the inner ear of guinea pig cochlea and human fetal cochlea (IHC based expression data, PMID: 31972369). Guinea pig cochlea was used as mice lack a true SCD5 orthologue due to rodent-specific gene loss, limiting their suitability as models for human SCD5-associated disease. In summary, there is limited evidence to support this gene-disease relationship and more evidence is needed to support a causal role. Simultaneously, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Hearing Loss GCEP on the meeting date 8/19/2026 (SOP Version 12).

hearing loss, autosomal dominant 79LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033668

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Deafness, autosomal dominant 79AD

Manifestation: Audiologic/Otolaryngologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31972369

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SCD5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 5

Hearing loss, autosomal dominant 79Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001037582.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar		4
missense	1 clinvar		45 clinvar	1 clinvar		47
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	45	5	0	51

Highest pathogenic variant AF is 0.000034072564

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001037582.3	RefSeq	NP_001032671.2	5	MANE Select
ENST00000319540.9	Ensembl	ENSP00000316329.4	5	MANE Select
NM_024906.3	RefSeq	NP_079182.2	4	Standard
ENST00000273908.4	Ensembl	ENSP00000273908.4	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Biosynthesis of unsaturated fatty acids - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
Metabolism of lipids
Fatty acyl-CoA biosynthesis

Biological Process

unsaturated fatty acid biosynthetic process
fatty-acyl-CoA biosynthetic process
oxidation-reduction process
monounsaturated fatty acid biosynthetic process

Molecular Function

stearoyl-CoA 9-desaturase activity
iron ion binding
oxidoreductase activity

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000319540
Coding exons: 5
Length: 169319
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.917	172	209	0.822	0.0000124	2155
Missense (PolyPhen)		47	67.628	0.69498		750
Synonymous	-0.500	90	84.2	1.07	0.00000474	674
Loss of Function	1.77	7	14.2	0.494	7.56e-7	144

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stearyl-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 (PubMed:15907797, PubMed:15610069). Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids. {ECO:0000269|PubMed:15610069, ECO:0000269|PubMed:15907797}.;

Recessive Scores

pRec: 0.295

Intolerance Scores

LoFtool: 0.225
RVIS EVS: 0.15
RVIS percentile EVS: 64.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.955

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium