C22ORF39

Chr 22

chromosome 22 open reading frame 39

Also known as: Pants

NCBI Gene: 128977 ENSG00000242259 UniProt: Q6P5X5

The protein negatively regulates long-term potentiation by stabilizing RTN4/Nogo-A interactions with its receptors and inhibiting AMPA receptor clustering at synapses. Mutations cause autosomal recessive intellectual disability with epilepsy and abnormal behavior. The gene shows low constraint to loss-of-function variation, consistent with recessive inheritance.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in negative regulation of long-term synaptic potentiation. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.77

Clinical Summary— C22ORF39

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

6 total variants — no pathogenic classifications of 6 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.77LOEUF

pLI 0.000

Z-score -0.07

OE 1.03 (0.58–1.77)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.20Z-score

OE missense 1.07 (0.89–1.29)

78 obs / 73.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.03 (0.58–1.77)

0≤0.351.4

Missense OE?1.07 (0.89–1.29)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 7 / 6.8Missense obs/exp: 78 / 73.1Syn Z: -0.67

ClinVar Variant Classifications

6 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

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392 pathogenic / likely-pathogenic (of 411) ClinVar copy-number / structural variants overlap C22ORF39 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →