DEGS1

delta 4-desaturase, sphingolipid 1, the group of Fatty acid desaturases

Basic information

Region (hg38): 1:224175756-224193441

Links

ENSG00000143753 ∙ NCBI:8560 ∙ OMIM:615843 ∙ HGNC:13709 ∙ Uniprot:O15121 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukodystrophy, hypomyelinating, 18 (Moderate), mode of inheritance: AR
• leukodystrophy, hypomyelinating, 18 (Strong), mode of inheritance: AR
• leukodystrophy, hypomyelinating, 18 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 18	AR	General	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	Neurologic	30620337; 30620338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DEGS1 gene.

• not provided (5 variants)
• Leukodystrophy (1 variants)
• Leukodystrophy, hypomyelinating, 18 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DEGS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				12	2	14
missense	1	4	38	3	3	49
nonsense	2	2	1			5
start loss		1	1			2
frameshift	1	2				3
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region	1		1			2
non coding				1	3	4
Total	4	11	40	16	8

Highest pathogenic variant AF is 0.0000197

Variants in DEGS1

This is a list of pathogenic ClinVar variants found in the DEGS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-224183111-C-T			Benign (May 12, 2021)
1-224183338-T-C		Leukodystrophy, hypomyelinating, 18	Likely pathogenic (-)
1-224183339-G-A			Uncertain significance (Nov 04, 2021)
1-224183357-G-A			Likely benign (Apr 16, 2024)
1-224183358-G-T			Pathogenic (Nov 06, 2023)
1-224183363-C-A		Inborn genetic diseases • DEGS1-related disorder	Benign/Likely benign (Jan 18, 2025)
1-224183385-C-T			Pathogenic (Oct 19, 2022)
1-224183396-C-T			Likely benign (Sep 01, 2022)
1-224183397-G-C			Uncertain significance (Oct 25, 2024)
1-224183400-C-G			Uncertain significance (Aug 01, 2024)
1-224183419-G-C			Likely pathogenic (Aug 09, 2022)
1-224183424-G-A			Uncertain significance (Oct 13, 2021)
1-224183438-C-A			Likely benign (Mar 26, 2024)
1-224189593-A-G		DEGS1-related disorder	Uncertain significance (Sep 12, 2022)
1-224189595-A-G		Inborn genetic diseases	Uncertain significance (Apr 20, 2024)
1-224189604-T-C		Leukodystrophy, hypomyelinating, 18	Conflicting classifications of pathogenicity (Mar 25, 2024)
1-224189613-A-T		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
1-224189629-G-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
1-224189641-G-C		Inborn genetic diseases	Uncertain significance (Sep 26, 2024)
1-224189652-C-T		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
1-224189663-G-A			Uncertain significance (Aug 21, 2022)
1-224189672-A-G		Leukodystrophy, hypomyelinating, 18	Uncertain significance (Aug 28, 2020)
1-224189675-G-A			Uncertain significance (Feb 10, 2022)
1-224189677-A-C			Likely benign (Oct 01, 2023)
1-224189677-A-G			Likely benign (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DEGS1	protein_coding	protein_coding	ENST00000323699	3	17686

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.139	0.843	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.804	137	166	0.824	0.00000810	2143
Missense in Polyphen		35	51.073	0.6853		676
Synonymous	0.663	52	58.4	0.890	0.00000315	588
Loss of Function	2.04	3	9.95	0.301	4.83e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000554	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.0000554	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has sphingolipid-delta-4-desaturase activity. Converts D-erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine). {ECO:0000269|PubMed:11937514}.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Neutrophil degranulation;Metabolism of lipids;Innate Immune System;Immune System;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.324

Intolerance Scores

• loftool: 0.276
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.478
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Degs1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: unsaturated fatty acid biosynthetic process;electron transport chain;sphingolipid biosynthetic process;neutrophil degranulation;ceramide biosynthetic process
• Cellular component: mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;membrane;specific granule membrane
• Molecular function: electron transfer activity;sphingolipid delta-4 desaturase activity