LEPROT

protein-coding

leptin receptor overlapping transcript

Gene summary

LEPROT is associated with the Golgi complex and endosomes and has a role in cell surface expression of growth hormone receptor (GHR; MIM 600946) and leptin receptor (OBR, or LEPR; MIM 601007), thereby altering receptor-mediated cell signaling (Couturier et al., 2007 [PubMed 18042720]; Touvier et al., 2009 [PubMed 19907080]).[supplied by OMIM, Jul 2010]

MANE transcript

NM_017526.5

Inheritance

—

ClinVar variants

U:11B:1

Top phenotype

Obesity due to leptin receptor gene deficiency

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr1:65,420,587-65,436,007

External References & Databases

Ensembl (ENSG00000213625)

Transcript & Mutation Effects

hg38 • Region Span ~15.4 kb

Loading mutation effect viewer...

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 LEPROT variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 11

not providedTotal: 3

Obesity due to leptin receptor gene deficiencyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017526.5. 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
missense			11 clinvar			11
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	11	1	0	12

Loading ClinVar variants...

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_017526.5	RefSeq	NP_059996.1	4	MANE Select
ENST00000371065.9	Ensembl	ENSP00000360104.4	4	MANE Select
NM_001198681.2	RefSeq	NP_001185610.1	4	Standard
NM_001198683.2	RefSeq	NP_001185612.1	3	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 JAK-STAT cascade
negative regulation of growth hormone receptor signaling pathway
positive regulation of protein targeting to mitochondrion
negative regulation of protein localization to cell surface

Molecular Function

signaling receptor binding
protein binding

Cellular Component

Golgi membrane
endosome
Golgi apparatus
endosome membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371065
Coding exons: 4
Length: 15421
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125735
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.708	55	71.9	0.765	0.00000369	835
Missense (PolyPhen)		11	22.436	0.49028		293
Synonymous	0.513	23	26.3	0.873	0.00000137	266
Loss of Function	1.76	1	5.42	0.184	2.28e-7	72

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)	0.000098	0.000097	rare
South Asian	0.000079	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negatively regulates leptin receptor (LEPR) cell surface expression, and thus decreases response to leptin. 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:18042720, ECO:0000269|PubMed:19907080}.;

Recessive Scores

pRec: 0.876

Intolerance Scores

LoFtool: 0.585
RVIS EVS: -0.01
RVIS percentile EVS: 52.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.636

Gene Damage Prediction

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