LYPLAL1

protein-coding

lysophospholipase like 1

Gene summary

Enables palmitoyl-(protein) hydrolase activity. Involved in negative regulation of cGAS/STING signaling pathway. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_138794.5

Inheritance

—

ClinVar variants

U:50B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr1:219,173,869-219,212,865

External References & Databases

Ensembl (ENSG00000143353)

Transcript & Mutation Effects

hg38 • Region Span ~39.0 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 LYPLAL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138794.5. 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			1 clinvar	1 clinvar		2
missense			45 clinvar	3 clinvar	1 clinvar	49
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	50	4	1	55

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138794.5	RefSeq	NP_620149.2	5	MANE Select
ENST00000366928.10	Ensembl	ENSP00000355895.5	5	MANE Select
NM_001300769.2	RefSeq	NP_001287698.1	4	Standard
NM_001300770.2	RefSeq	NP_001287699.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein depalmitoylation
biological_process

Molecular Function

lysophospholipase activity
palmitoyl-(protein) hydrolase activity
carboxylic ester hydrolase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366928
Coding exons: 5
Length: 39022
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125748
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.23	159	121	1.31	0.00000526	1537
Missense (PolyPhen)		48	40.606	1.1821		509
Synonymous	-0.483	48	43.9	1.09	0.00000198	439
Loss of Function	0.656	8	10.3	0.779	4.32e-7	137

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000093	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.0010	0.0010	notable
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has depalmitoylating activity toward KCNMA1. Does not exhibit phospholipase nor triacylglycerol lipase activity, able to hydrolyze only short chain substrates due to its shallow active site. {ECO:0000269|PubMed:22052940, ECO:0000269|PubMed:22399288}.;

Recessive Scores

pRec: 0.0773

Intolerance Scores

LoFtool: 0.842
RVIS EVS: 0.22
RVIS percentile EVS: 68.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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