C15ORF40

Chr 15

chromosome 15 open reading frame 40

NCBI Gene: 123207 ENSG00000169609 UniProt: Q8WUR7

The protein encoded by this gene localizes to the mitochondrion, though its specific function remains unclear. Mutations cause autosomal recessive intellectual disability with seizures and growth retardation, typically manifesting in early childhood. The gene shows relatively low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq

Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 0.96

Clinical Summary— C15ORF40

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

25 VUS of 44 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?

0.96LOEUF

pLI 0.186

Z-score 1.66

OE 0.30 (0.12–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.63Z-score

OE missense 1.19 (1.01–1.39)

106 obs / 89.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.30 (0.12–0.96)

0≤0.351.4

Missense OE?1.19 (1.01–1.39)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 2 / 6.6Missense obs/exp: 106 / 89.4Syn Z: -1.39

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

VUS25

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	24	25
Likely Benign	0	2	2
Benign	0	0	0
Total	1	26	27

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap C15ORF40 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →