LPAR6

protein-coding

lysophosphatidic acid receptor 6, the group of Lysophosphatidic acid receptors

Gene summary

The protein encoded by this gene belongs to the family of G-protein coupled receptors, that are preferentially activated by adenosine and uridine nucleotides. This gene aligns with an internal intron of the retinoblastoma susceptibility gene in the reverse orientation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

Previous symbols:

P2RY5

MANE transcript

NM_001162498.3

Inheritance

AR, AD

ClinVar variants

P:19U:47B:33

Top phenotype

Hypotrichosis 8

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr13:48,389,567-48,444,704

External References & Databases

Ensembl (ENSG00000139679)

Transcript & Mutation Effects

hg38 • Region Span ~55.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypotrichosis 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010206

Submitter: Labcorp Genetics (formerly Invitae)

hypotrichosis simplexSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018914

Submitter: Orphanet

hypotrichosis 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010206

Submitter: G2P

wooly hair, autosomal recessive 1, with or without hypotrichosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0800312

Submitter: PanelApp Australia

isolated familial wooly hair disorderSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008686

Submitter: Orphanet

hypotrichosis 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0010206

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Hypotrichosis 8AR

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 18461368; 18297070; 18297072; 21070332; 21426374

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LPAR6 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 43

not providedTotal: 27

Hypotrichosis 8Total: 21

RetinoblastomaTotal: 12

LPAR6-related disorderTotal: 3

Wooly hair, autosomal recessive 1, with or without hypotrichosisTotal: 3

not specifiedTotal: 2

Wooly hair, autosomal recessive 3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001162498.3. 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				17 clinvar		17
missense		9 clinvar	46 clinvar	7 clinvar	3 clinvar	65
nonsense	1 clinvar	1 clinvar		1 clinvar		3
start loss	1 clinvar					1
frameshift	2 clinvar	5 clinvar	1 clinvar	1 clinvar	4 clinvar	13
splice donor/acceptor (+/-2bp)						0
Total	4	15	47	26	7	99

Highest pathogenic variant AF is 0.000022578368

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001162498.3	RefSeq	NP_001155970.1	1	MANE Select
ENST00000620633.5	Ensembl	ENSP00000482660.1	1	MANE Select
NM_001162497.3	RefSeq	NP_001155969.1	1	Standard
NM_001377316.2	RefSeq	NP_001364245.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lpar6a	Danio rerio	Structure: intersegmental vessel Quality: decreased functionality abnormal

Gene / Model

Organism

Observed Phenotype

lpar6a

Danio rerio

Structure: intersegmental vessel

Quality: decreased functionality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Phospholipase D signaling pathway - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Focal Adhesion-PI3K-Akt-mTOR-signaling pathway

Biological Process

blastocyst hatching
G protein-coupled receptor signaling pathway
positive regulation of Rho protein signal transduction
positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway

Molecular Function

G protein-coupled receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378434
Coding exons: 1
Length: 55134
Individuals with no LoFs: 125680
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125722
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.114	174	178	0.976	0.00000819	2280
Missense (PolyPhen)		69	70.559	0.9779		946
Synonymous	0.727	56	63.4	0.884	0.00000308	656
Loss of Function	1.01	6	9.33	0.643	4.42e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00059	0.00059	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to oleoyl-L-alpha-lysophosphatidic acid (LPA). Intracellular cAMP is involved in the receptor activation. Important for the maintenance of hair growth and texture. {ECO:0000269|PubMed:18297070}.;
Disease: DISEASE: Woolly hair autosomal recessive 1 with or without hypotrichosis (ARWH1) [MIM:278150]: A hair shaft disorder characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, woolly hair grows slowly and stops growing after a few inches. Under light microscopy, woolly hair shows some structural anomalies, including trichorrhexis nodosa and tapered ends. Some individuals exhibit features of hypotrichosis. {ECO:0000269|PubMed:18297072}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypotrichosis 8 (HYPT8) [MIM:278150]: A condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed. {ECO:0000269|PubMed:18297070}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.937
RVIS EVS: 0.02
RVIS percentile EVS: 55.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.192

Gene Damage Prediction

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