LPAR6

Chr 13AR

lysophosphatidic acid receptor 6

Also known as: ARWH1, HYPT8, LAH3, LPA-6, P2RY5, P2Y5

NCBI Gene: 10161 ENSG00000139679 UniProt: P43657 OMIM: 609239

The LPAR6 protein is a G-protein coupled receptor that binds lysophosphatidic acid and is important for maintaining hair growth and texture through cAMP signaling pathways. Mutations cause autosomal recessive hypotrichosis and woolly hair disorders characterized by sparse, abnormally textured hair that is typically apparent from birth or early childhood. These conditions primarily affect hair follicle development and maintenance without significant involvement of other organ systems.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypotrichosis 8MIM #278150

Woolly hair, autosomal recessive 1, with or without hypotrichosisMIM #278150

UniProtWoolly hair autosomal recessive 1 with or without hypotrichosis

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hypotrichosis 8; Woolly hair, autosomal recessive 1, with or without hypotrichosis; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.27

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.001

Z-score 1.01

OE 0.64 (0.35–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.11Z-score

OE missense 0.98 (0.86–1.11)

174 obs / 178.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.35–1.27)

0≤0.351.4

Missense OE?0.98 (0.86–1.11)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 6 / 9.3Missense obs/exp: 174 / 178.3Syn Z: 0.73

Background carrier burden — how many people carry a rare variant somewhere in LPAR6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

412 rare PASS variants

Rare truncating (LoF)

1 in 3,000

63 rare PASS variants

Rare synonymous (reference)

1 in 660

145 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LPAR6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 410	1 in 4,400
South Asian	~43k	1 in 140	1 in 620
Remaining (unassigned)	~30k	1 in 160	1 in 2,200
European (Finnish)	~27k	1 in 470	none seen
Admixed American	~22k	1 in 200	1 in 800
African / African American	~21k	1 in 250	1 in 3,300
East Asian	~20k	1 in 150	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 520	none seen
Middle Eastern	~2,884	1 in 170	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓