LEPROT

leptin receptor overlapping transcript

Basic information

Region (hg38): 1:65420586-65436007

Links

ENSG00000213625 ∙ NCBI:54741 ∙ OMIM:613461 ∙ HGNC:29477 ∙ Uniprot:O15243 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LEPROT gene.

• Obesity due to leptin receptor gene deficiency (6 variants)
• Monogenic Non-Syndromic Obesity (4 variants)
• Inborn genetic diseases (4 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LEPROT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			5			5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3		2	5
Total	0	0	8	1	2

Variants in LEPROT

This is a list of pathogenic ClinVar variants found in the LEPROT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-65420651-C-T		Obesity due to leptin receptor gene deficiency	Uncertain significance (Jan 12, 2018)
1-65420675-C-A		Obesity due to leptin receptor gene deficiency	Uncertain significance (Jan 13, 2018)
1-65420676-C-T		Monogenic Non-Syndromic Obesity • Obesity due to leptin receptor gene deficiency	Uncertain significance (Jan 12, 2018)
1-65420715-T-C		Obesity due to leptin receptor gene deficiency • Monogenic Non-Syndromic Obesity	Benign (Jun 14, 2016)
1-65420717-C-T		Monogenic Non-Syndromic Obesity • Obesity due to leptin receptor gene deficiency	Uncertain significance (Jun 14, 2016)
1-65421440-G-A			Likely benign (Jun 02, 2018)
1-65425307-C-T		Obesity due to leptin receptor gene deficiency • Monogenic Non-Syndromic Obesity	Conflicting classifications of pathogenicity (May 20, 2021)
1-65425308-G-A		not specified	Uncertain significance (Nov 10, 2022)
1-65425348-T-G		Obesity due to leptin receptor gene deficiency	Uncertain significance (Jan 13, 2018)
1-65425500-T-A			Benign (May 21, 2021)
1-65429863-G-A		not specified	Uncertain significance (Oct 22, 2021)
1-65429968-C-T		not specified	Uncertain significance (Jun 21, 2023)
1-65429999-T-C		not specified	Uncertain significance (Sep 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LEPROT	protein_coding	protein_coding	ENST00000371065	4	15421

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.438	0.535	125722	0	13	125735	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.708	55	71.9	0.765	0.00000369	835
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000982	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000785	0.0000653
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.232
• hipred: Y
• hipred_score: 0.612
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.636

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Leprot
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype

Gene ontology

• 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
• Cellular component: Golgi membrane;endosome;Golgi apparatus;endosome membrane;integral component of membrane
• Molecular function: signaling receptor binding;protein binding