LSR

protein-coding

lipolysis stimulated lipoprotein receptor, the group of Immunoglobulin like domain containing

Gene summary

Predicted to be involved in several processes, including establishment of skin barrier; protein localization to tricellular tight junction; and tricellular tight junction assembly. Predicted to act upstream of or within maintenance of blood-brain barrier. Located in plasma membrane and tight junction. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_205834.4

Inheritance

ClinVar variants

P:4U:149B:52

Top phenotype

LSR-related condition

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr19:35,248,330-35,267,964

External References & Databases

Ensembl (ENSG00000105699)

Transcript & Mutation Effects

hg38 • Region Span ~19.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intrahepatic cholestasisMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0019072

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LSR variants in ClinVar

8 Conditions Cataloged

not providedTotal: 120

not specifiedTotal: 107

LSR-related conditionTotal: 39

Progressive familial intrahepatic cholestasisTotal: 3

Hepatobiliary disorderTotal: 2

LSR-related disorderTotal: 2

Cholestasis, progressive familial intrahepatic, 6Total: 1

Progressive familial intrahepatic cholestasis type 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_205834.4. 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			2 clinvar	39 clinvar	3 clinvar	44
missense		1 clinvar	138 clinvar	8 clinvar	2 clinvar	149
nonsense			2 clinvar			2
start loss			2 clinvar			2
frameshift		2 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	0	4	149	47	5	205

Highest pathogenic variant AF is 0.000031483818

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_205834.4	RefSeq	NP_991403.2	10	MANE Select
ENST00000605618.6	Ensembl	ENSP00000474797.2	10	MANE Select
NM_001260489.2	RefSeq	NP_001247418.2	9	Standard
NM_001260490.2	RefSeq	NP_001247419.2	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lsr	Danio rerio	Structure: pancreatic B cell Quality: mislocalised abnormal

Gene / Model

Organism

Observed Phenotype

lsr

Danio rerio

Structure: pancreatic B cell

Quality: mislocalised

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

LDL clearance
VLDL clearance
Plasma lipoprotein clearance
Transport of small molecules
EGFR1

Biological Process

liver development
regulation of lipid metabolic process
establishment of blood-brain barrier
tricellular tight junction assembly

Cellular Component

plasma membrane
integral component of membrane
very-low-density lipoprotein particle
low-density lipoprotein particle
chylomicron

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361790
Coding exons: 10
Length: 19635
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.629	444	408	1.09	0.0000244	4125
Missense (PolyPhen)		148	162.52	0.91064		1598
Synonymous	-0.142	181	179	1.01	0.0000113	1355
Loss of Function	2.09	16	27.9	0.573	0.00000140	301

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.199

Intolerance Scores

LoFtool: 0.922
RVIS EVS: -0.86
RVIS percentile EVS: 10.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.985

Gene Damage Prediction

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