C11ORF68

Chr 11

chromosome 11 open reading frame 68

Also known as: BLES03, P5326

NCBI Gene: 83638 ENSG00000175573 UniProt: Q9H3H3

The protein encoded by this gene enables RNA binding activity. Mutations cause autosomal recessive spastic paraplegia with intellectual disability, typically presenting in early childhood with progressive spasticity primarily affecting the lower extremities and developmental delays. The gene shows moderate tolerance to loss-of-function variants.

ResearchSummary from RefSeq

Enables RNA binding activity. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.84

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.246

Z-score 1.85

OE 0.27 (0.11–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.33Z-score

OE missense 0.71 (0.62–0.83)

123 obs / 172.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.11–0.84)

0≤0.351.4

Missense OE?0.71 (0.62–0.83)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 2 / 7.5Missense obs/exp: 123 / 172.2Syn Z: 0.58

Background carrier burden — how many people carry a rare variant somewhere in C11ORF68?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

456 rare PASS variants

Rare truncating (LoF)

1 in 4,700

60 rare PASS variants

Rare synonymous (reference)

1 in 470

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C11ORF68. 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 340	1 in 7,000
South Asian	~43k	1 in 170	1 in 8,300
Remaining (unassigned)	~30k	1 in 180	1 in 6,000
European (Finnish)	~27k	1 in 720	1 in 2,300
Admixed American	~22k	1 in 200	≈ 1 in 5,600
African / African American	~21k	1 in 160	≈ 1 in 9,200
East Asian	~20k	1 in 270	1 in 1,100
Ashkenazi Jewish	~13k	1 in 300	none seen
Middle Eastern	~2,884	1 in 130	≈ 1 in 2,900

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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓