MIX23

Chr 3

mitochondrial matrix import factor 23

Also known as: CCDC58

NCBI Gene: 131076 ENSG00000160124 UniProt: Q4VC31 OMIM: 620713

MIX23 encodes a mitochondrial protein with unknown specific function. Mutations cause autosomal recessive developmental disorders, though the clinical phenotype remains poorly characterized. This gene shows low constraint against loss-of-function variants, suggesting haploinsufficiency may not be the primary disease mechanism.

OMIM ResearchSummary from RefSeq

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

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.14

Clinical Summary— MIX23

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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

15 VUS of 27 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.004

Z-score 1.29

OE 0.54 (0.28–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.90Z-score

OE missense 0.71 (0.57–0.89)

53 obs / 74.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.28–1.14)

0≤0.351.4

Missense OE?0.71 (0.57–0.89)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 5 / 9.2Missense obs/exp: 53 / 74.8Syn Z: -0.54

This gene — mechanism propensity

0.6646th %ile

GOF

0.6346th %ile

LOF

0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

27 submitted variants in ClinVar

ClinVar

Classification Summary

VUS15

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	15	15
Likely Benign	0	0
Benign	0	0
Total	15	15

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap MIX23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →