LEPROTL1

protein-coding

leptin receptor overlapping transcript like 1

Gene summary

Enables identical protein binding activity. Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway and negative regulation of growth hormone receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_015344.3

Inheritance

—

ClinVar variants

U:9

Top phenotype

Hereditary breast ovarian cancer syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr8:30,095,408-30,177,208

External References & Databases

Ensembl (ENSG00000104660)

Transcript & Mutation Effects

hg38 • Region Span ~81.8 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 LEPROTL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 7

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015344.3. 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
missense			8 clinvar			8
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	9	0	0	9

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015344.3	RefSeq	NP_056159.2	4	MANE Select
ENST00000321250.13	Ensembl	ENSP00000314625.8	4	MANE Select
NM_001128208.2	RefSeq	NP_001121680.1	4	Standard
ENST00000442880.6	Ensembl	ENSP00000412803.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

late endosome to vacuole transport via multivesicular body sorting pathway
negative regulation of protein localization to cell surface

Molecular Function

protein binding

Cellular Component

endosome
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000523116
Coding exons: 4
Length: 81811
Individuals with no LoFs: 116475
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 116476
p: 0.00000429

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.942	65	90.2	0.721	0.00000444	1069
Missense (PolyPhen)		13	29.644	0.43854		358
Synonymous	0.424	32	35.2	0.909	0.00000196	363
Loss of Function	1.90	0	4.21	0.00	1.75e-7	65

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000092	0.0000092	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negatively regulates growth hormone (GH) receptor cell surface expression in liver. May play a role in liver resistance to GH during periods of reduced nutrient availability. {ECO:0000269|PubMed:19907080}.;

Recessive Scores

pRec: 0.0924

Intolerance Scores

LoFtool: 0.454
RVIS EVS: 0.48
RVIS percentile EVS: 79.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.571

Gene Damage Prediction

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