C3ORF52

Chr 3AR

chromosome 3 open reading frame 52

Also known as: HYPT15, TTMP

NCBI Gene: 79669 ENSG00000114529 UniProt: Q5BVD1 OMIM: 611956

This protein facilitates LIPH-mediated synthesis of 2-acyl lysophosphatidic acid (LPA), a bioactive lipid mediator necessary for hair formation and growth. Mutations cause hypotrichosis 15, an autosomal recessive condition characterized by sparse hair development. The gene shows low constraint to loss-of-function variation (pLI 0.00009, LOEUF 1.8), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Located in plasma membrane. Implicated in hypotrichosis 15. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypotrichosis 15MIM #620177

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hypotrichosis 15; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.79

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.79LOEUF

pLI 0.000

Z-score -0.06

OE 1.03 (0.55–1.79)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.86Z-score

OE missense 0.78 (0.66–0.93)

97 obs / 123.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.03 (0.55–1.79)

0≤0.351.4

Missense OE?0.78 (0.66–0.93)

0≤0.61.4

Synonymous OE?0.75

0≤1.21.6

LoF obs/exp: 6 / 5.9Missense obs/exp: 97 / 123.8Syn Z: 1.41

Background carrier burden — how many people carry a rare variant somewhere in C3ORF52?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

411 rare PASS variants

Rare truncating (LoF)

1 in 300

88 rare PASS variants

Rare synonymous (reference)

1 in 290

143 rare PASS variants

Rare missense and truncating variants are carried at similar rates in C3ORF52; this gene does not show strong loss-of-function constraint by this measure. 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 170	1 in 320
South Asian	~43k	1 in 100	1 in 2,100
Remaining (unassigned)	~30k	1 in 62	1 in 230
European (Finnish)	~27k	1 in 290	1 in 1,000
Admixed American	~22k	1 in 100	1 in 510
African / African American	~21k	1 in 120	1 in 310
East Asian	~20k	1 in 120	1 in 1,000
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 110	1 in 260

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): 5 of 6 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 6.? see exons ↓