C17ORF78

Chr 17

chromosome 17 open reading frame 78

NCBI Gene: 284099 ENSG00000278505 UniProt: Q8N4C9

The C17ORF78 protein is predicted to be located in cellular membranes, though its specific function remains unclear. Mutations cause autosomal recessive developmental disorders affecting the nervous system. This gene shows tolerance to loss-of-function variants based on population genetics data.

ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.64

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.64LOEUF

pLI 0.000

Z-score -0.16

OE 1.05 (0.68–1.64)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.75Z-score

OE missense 0.82 (0.70–0.96)

111 obs / 135.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.05 (0.68–1.64)

0≤0.351.4

Missense OE?0.82 (0.70–0.96)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 13 / 12.4Missense obs/exp: 111 / 135.5Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in C17ORF78?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

285 rare PASS variants

Rare truncating (LoF)

1 in 1,800

53 rare PASS variants

Rare synonymous (reference)

1 in 550

104 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for C17ORF78. 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 600	1 in 1,800
South Asian	~43k	1 in 200	1 in 1,600
Remaining (unassigned)	~30k	1 in 120	1 in 2,700
European (Finnish)	~27k	1 in 680	≈ 1 in 27,000
Admixed American	~22k	1 in 270	1 in 1,900
African / African American	~21k	1 in 200	1 in 3,100
East Asian	~20k	1 in 240	1 in 3,300
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	1 in 170	1 in 580

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 7.? see exons ↓