ORMDL1

protein-coding

ORMDL sphingolipid biosynthesis regulator 1

Gene summary

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

MANE transcript

NM_016467.5

Inheritance

—

ClinVar variants

U:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr2:189,766,012-189,784,364

External References & Databases

Ensembl (ENSG00000128699)

Transcript & Mutation Effects

hg38 • Region Span ~18.4 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 ORMDL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 16

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016467.5. 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			17 clinvar			17
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	17	0	0	17

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 107 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016467.5	RefSeq	NP_057551.1	3	MANE Select
ENST00000392349.9	Ensembl	ENSP00000376160.4	3	MANE Select
NM_001128150.2	RefSeq	NP_001121622.1	3	Standard
NM_001371384.1	RefSeq	NP_001358313.1	4	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
endoplasmic reticulum membrane
integral component of membrane
SPOTS complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325795
Coding exons: 3
Length: 14049
Individuals with no LoFs: 125649
Homozygous LoFs: 0
Heterozygous LoFs: 98
Defined: 125747
p: 0.000390

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.777	66	86.3	0.765	0.00000467	998
Missense (PolyPhen)		34	45.849	0.74157		556
Synonymous	0.597	25	29.1	0.859	0.00000145	305
Loss of Function	1.36	2	5.41	0.370	2.29e-7	67

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.0028	0.0028	notable
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00023	0.00023	rare
Other	0.00083	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.459
RVIS EVS: -0.05
RVIS percentile EVS: 49.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.645

Gene Damage Prediction

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