C8ORF74

Chr 8

chromosome 8 open reading frame 74

NCBI Gene: 203076 ENSG00000171060 UniProt: Q6P047

The protein encoded by this gene has unknown function. Mutations cause autosomal recessive spastic paraplegia with intellectual disability, typically presenting in early childhood with progressive spasticity affecting the lower limbs and developmental delays. This gene shows minimal constraint against loss-of-function variants in population databases.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.94

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?

1.94LOEUF

pLI 0.000

Z-score -1.65

OE 1.60 (1.02–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.79Z-score

OE missense 1.39 (1.25–1.55)

234 obs / 168.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.60 (1.02–1.94)

0≤0.351.4

Missense OE?1.39 (1.25–1.55)

0≤0.61.4

Synonymous OE?1.36

0≤1.21.6

LoF obs/exp: 14 / 8.7Missense obs/exp: 234 / 168.6Syn Z: -2.55

Background carrier burden — how many people carry a rare variant somewhere in C8ORF74?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

573 rare PASS variants

Rare truncating (LoF)

1 in 420

119 rare PASS variants

Rare synonymous (reference)

1 in 170

282 rare PASS variants

Rare missense and truncating variants are carried at similar rates in C8ORF74; 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 120	1 in 380
South Asian	~43k	1 in 90	1 in 240
Remaining (unassigned)	~30k	1 in 66	1 in 390
European (Finnish)	~27k	1 in 350	1 in 540
Admixed American	~22k	1 in 92	1 in 640
African / African American	~21k	1 in 46	1 in 260
East Asian	~20k	1 in 94	1 in 1,600
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 70	1 in 530

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): 4 of 4 coding exons well covered in gnomAD exomes. Genomes: 3 of 4 (exon 2 below).? see exons ↓