KDSR

3-ketodihydrosphingosine reductase, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 18:63327726-63367228

Previous symbols: [ "FVT1" ]

Links

ENSG00000119537 ∙ NCBI:2531 ∙ OMIM:136440 ∙ HGNC:4021 ∙ Uniprot:Q06136 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• erythrokeratodermia variabilis et progressiva 4 (Strong), mode of inheritance: AR
• erythrokeratodermia variabilis et progressiva 4 (Strong), mode of inheritance: AR
• erythrokeratodermia variabilis (Supportive), mode of inheritance: AD
• erythrokeratodermia variabilis (Supportive), mode of inheritance: AD
• erythrokeratodermia variabilis et progressiva 4 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Erythrokeratodermia variabilis et progressiva 4	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	Dermatologic	28575652

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDSR 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					2	2
missense		1	14	1		16
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				2	1	3
Total	0	2	14	3	3

Variants in KDSR

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

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

Position	Type	Phenotype	Significance	ClinVar
18-63331816-C-G		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
18-63331825-A-G		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
18-63331829-A-G		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
18-63331831-C-T		Inborn genetic diseases	Uncertain significance (Jun 28, 2024)
18-63331834-C-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2024)
18-63331895-T-A		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
18-63335257-C-T		Erythrokeratodermia variabilis et progressiva 4	Likely pathogenic (-)
18-63335342-C-A		Inborn genetic diseases	Uncertain significance (Oct 19, 2024)
18-63338803-G-A			Benign (Oct 02, 2018)
18-63338838-G-C			Uncertain significance (Jul 17, 2021)
18-63338864-A-G		Inborn genetic diseases	Uncertain significance (Jun 30, 2024)
18-63338903-T-A			Likely benign (Dec 31, 2021)
18-63350940-T-A		Erythrokeratodermia variabilis et progressiva 4	Pathogenic (Jun 13, 2017)
18-63350953-C-T		Erythrokeratodermia variabilis et progressiva 4	Likely pathogenic (-)
18-63350976-T-A		Inborn genetic diseases	Uncertain significance (Mar 19, 2024)
18-63350985-A-G			Uncertain significance (Oct 25, 2022)
18-63351049-C-T		Inborn genetic diseases	Uncertain significance (Aug 30, 2021)
18-63355190-A-C			Likely benign (Aug 04, 2023)
18-63355208-A-C			Likely pathogenic (Feb 14, 2024)
18-63355214-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
18-63355225-A-T		Inborn genetic diseases	Uncertain significance (May 04, 2022)
18-63355245-C-G		Inborn genetic diseases	Likely benign (Mar 14, 2023)
18-63355558-C-T		Erythrokeratodermia variabilis et progressiva 4	Benign (Jan 29, 2024)
18-63355565-T-G		Erythrokeratodermia variabilis et progressiva 4	Pathogenic (Jun 13, 2017)
18-63362764-A-G			Benign (May 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDSR	protein_coding	protein_coding	ENST00000406396	10	39785

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.117	0.882	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.938	146	182	0.804	0.00000955	2154
Missense in Polyphen		46	69.519	0.66169		719
Synonymous	0.582	59	65.0	0.908	0.00000342	659
Loss of Function	2.87	5	18.2	0.275	9.32e-7	216

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000979	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.000101	0.0000980
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reduction of 3-ketodihydrosphingosine (KDS) to dihydrosphingosine (DHS). {ECO:0000269|PubMed:28575652}.
• Disease: DISEASE: Erythrokeratodermia variabilis et progressiva 4 (EKVP4) [MIM:617526]: A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. {ECO:0000269|PubMed:28575652}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Sphingolipid Metabolism;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;ceramide <i>de novo</i> biosynthesis;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.306
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.718
• hipred: Y
• hipred_score: 0.595
• ghis: 0.639

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.686

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kdsr

Gene ontology

• Biological process: 3-keto-sphinganine metabolic process;sphingolipid biosynthetic process;oxidation-reduction process
• Cellular component: extracellular space;endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: 3-dehydrosphinganine reductase activity