ORMDL3

ORMDL sphingolipid biosynthesis regulator 3

Basic information

Region (hg38): 17:39921040-39927601

Links

ENSG00000172057 ∙ NCBI:94103 ∙ OMIM:610075 ∙ HGNC:16038 ∙ Uniprot:Q8N138 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ORMDL3 gene.

• Inborn genetic diseases (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ORMDL3 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						0
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	0

Variants in ORMDL3

This is a list of pathogenic ClinVar variants found in the ORMDL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-39922663-T-G		not specified	Uncertain significance (Nov 03, 2022)
17-39923125-T-A		not specified	Uncertain significance (May 09, 2023)
17-39924082-G-A		not specified	Uncertain significance (Mar 02, 2023)
17-39924098-C-T		not specified	Uncertain significance (Oct 29, 2021)
17-39924130-G-A		not specified	Uncertain significance (Jan 31, 2022)
17-39924131-A-G		not specified	Uncertain significance (Jul 26, 2022)
17-39924143-C-T		not specified	Uncertain significance (Dec 19, 2022)
17-39924179-C-T		not specified	Uncertain significance (Jul 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ORMDL3	protein_coding	protein_coding	ENST00000394169	3	6561

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.783	0.211	125736	0	5	125741	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	64	101	0.632	0.00000652	1008
Missense in Polyphen		21	31.686	0.66275		375
Synonymous	-1.19	56	45.7	1.22	0.00000341	310
Loss of Function	2.09	0	5.06	0.00	2.16e-7	55

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of sphingolipid synthesis. May indirectly regulate endoplasmic reticulum-mediated Ca(+2) signaling. {ECO:0000269|PubMed:20182505}.
• Pathway: Neutrophil degranulation;Metabolism of lipids;Innate Immune System;Immune System;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.254
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.632
• hipred: Y
• hipred_score: 0.619
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.949

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ormdl3

Gene ontology

• Biological process: ceramide metabolic process;neutrophil degranulation;cellular sphingolipid homeostasis;negative regulation of ceramide biosynthetic process
• Cellular component: endoplasmic reticulum;plasma membrane;integral component of membrane;secretory granule membrane;SPOTS complex;specific granule membrane
• Molecular function: protein binding