C18ORF54

Chr 18

chromosome 18 open reading frame 54

Also known as: LAS2

NCBI Gene: 162681 ENSG00000166845 UniProt: Q8IYD9 OMIM: 613258

The protein is predicted to negatively regulate cell population proliferation and is located in the extracellular region. Mutations in this gene cause developmental delays and intellectual disability with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 1.11

OE 0.70 (0.44–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.57Z-score

OE missense 1.11 (1.00–1.25)

218 obs / 195.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.70 (0.44–1.16)

0≤0.351.4

Missense OE?1.11 (1.00–1.25)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 11 / 15.8Missense obs/exp: 218 / 195.7Syn Z: 0.35

Background carrier burden — how many people carry a rare variant somewhere in C18ORF54?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

736 rare PASS variants

Rare truncating (LoF)

1 in 420

134 rare PASS variants

Rare synonymous (reference)

1 in 140

230 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C18ORF54. 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 160	1 in 780
South Asian	~43k	1 in 60	1 in 1,100
Remaining (unassigned)	~30k	1 in 55	1 in 410
European (Finnish)	~27k	1 in 620	1 in 2,300
Admixed American	~22k	1 in 58	1 in 400
African / African American	~21k	1 in 100	1 in 670
East Asian	~20k	1 in 69	1 in 680
Ashkenazi Jewish	~13k	1 in 500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 69	1 in 360

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 7 coding exons well covered in gnomAD exomes; exons 6, 8 marginal. Genomes: all 7.? see exons ↓