TIMMDC1

Chr 3AR

translocase of inner mitochondrial membrane domain containing 1

Also known as: C3orf1, MC1DN31

NCBI Gene: 51300ENSG00000113845UniProt: Q9NPL8

Predicted to be involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion and nucleoplasm. Implicated in nuclear type mitochondrial complex I deficiency 31. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 31MIM #618251
AR
154
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TIMMDC1
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 87 VUS of 154 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.27LOEUF
pLI 0.000
Z-score 0.73
OE 0.81 (0.54–1.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.00Z-score
OE missense 1.00 (0.88–1.14)
156 obs / 156.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.81 (0.54–1.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.88–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 14 / 17.3Missense obs/exp: 156 / 156.2Syn Z: -1.01

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic7
VUS87
Likely Benign30
Benign12
Conflicting3
15
Pathogenic
7
Likely Pathogenic
87
VUS
30
Likely Benign
12
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
4
1
2
0
7
VUS
3
70
13
1
87
Likely Benign
0
3
13
14
30
Benign
0
3
7
2
12
Conflicting
—3
Total7775017154

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

View in ClinVar →

Protein Context — Lollipop Plot

TIMMDC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex I deficiency, nuclear type 31

MIM #618251

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Multi-omics characterization of esophageal squamous cell carcinoma identifies molecular subtypes and therapeutic targets.
Zhao D et al.·JCI Insight
2024
Integrated bioinformatics and experiment validation reveal cuproptosis-related biomarkers and therapeutic targets in sepsis-induced myocardial dysfunction.
Shi X et al.·BMC Infect Dis
2025
Deep intronic TIMMDC1 variant delays diagnosis of rapidly progressive complex I deficiency.
Naber M et al.·Eur J Med Genet
2021Case report
Potentially Critical Roles of NDUFB5, TIMMDC1, and VDAC3 in the Progression of Septic Cardiomyopathy Through Integrated Bioinformatics Analysis.
Kang K et al.·DNA Cell Biol
2020
Neuropathological hallmarks of antenatal mitochondrial diseases with a corpus callosum defect.
Boutaud L et al.·Brain
2023
Genetic diagnosis of Mendelian disorders via RNA sequencing.
Kremer LS et al.·Nat Commun
2017
A patient with homozygous nonsense variants in two Leigh syndrome disease genes: Distinguishing a dual diagnosis from a hypomorphic protein-truncating variant.
Lake NJ et al.·Hum Mutat
2019Case report
Comprehensive study of W06A7.4 and TMEM144 mediated pathways in aging: insights from Caenorhabditis elegans to human.
Wang LF et al.·Mol Genet Genomics
2025
Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype.
Alston CL et al.·Am J Hum Genet
2016Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools