ORMDL2

protein-coding

ORMDL sphingolipid biosynthesis regulator 2

Gene summary

Involved in ceramide metabolic process. Acts upstream of or within negative regulation of ceramide biosynthetic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014182.5

Inheritance

—

ClinVar variants

U:21B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr12:55,818,041-55,821,879

External References & Databases

Ensembl (ENSG00000123353)

Transcript & Mutation Effects

hg38 • Region Span ~3.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ORMDL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 20

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014182.5. 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						0
missense			19 clinvar	1 clinvar	1 clinvar	21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	21	1	1	23

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014182.5	RefSeq	NP_054901.1	3	MANE Select
ENST00000243045.10	Ensembl	ENSP00000243045.5	3	MANE Select
ENST00000548974.1	Ensembl	ENSP00000448788.1	3	Standard
ENST00000548974.2	Ensembl	ENSP00000448788.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Sphingolipid de novo biosynthesis
Sphingolipid metabolism

Biological Process

ceramide metabolic process
cellular sphingolipid homeostasis
negative regulation of ceramide biosynthetic process

Cellular Component

endoplasmic reticulum
integral component of membrane
SPOTS complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000243045
Coding exons: 3
Length: 3961
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125747
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.462	78	90.3	0.863	0.00000499	992
Missense (PolyPhen)		21	24.894	0.84357		307
Synonymous	0.185	36	37.4	0.962	0.00000214	313
Loss of Function	1.68	2	6.71	0.298	4.56e-7	62

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negative regulator of sphingolipid synthesis. {ECO:0000269|PubMed:20182505}.;

Recessive Scores

pRec: 0.0790

Intolerance Scores

LoFtool: 0.240
RVIS EVS: -0.14
RVIS percentile EVS: 42.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.545

Gene Damage Prediction

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