MITD1

Chr 2

microtubule interacting and trafficking domain containing 1

The protein regulates ESCRT-III complex activity and is required for efficient abscission during cytokinesis, the final step of cell division where daughter cells separate. Mutations cause mitochondrial DNA depletion syndrome, which typically presents in infancy or early childhood with multisystem involvement including liver dysfunction, muscle weakness, and neurological deterioration, following autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants, consistent with recessive disease manifestation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
37
P/LP submissions
17%
P/LP missense
1.08
LOEUF
DN
Mechanism· predicted
Clinical SummaryMITD1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 102 VUS of 171 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.000
Z-score 1.34
OE 0.64 (0.391.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.57Z-score
OE missense 0.86 (0.731.00)
111 obs / 129.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.391.08)
00.351.4
Missense OE0.86 (0.731.00)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 10 / 15.7Missense obs/exp: 111 / 129.3Syn Z: -0.21
DN
0.6743th %ile
GOF
0.5169th %ile
LOF
0.2969th %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

171 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic10
VUS102
Likely Benign24
Benign9
Conflicting7
13
Pathogenic
10
Likely Pathogenic
102
VUS
24
Likely Benign
9
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
12
0
13
Likely Pathogenic
0
3
7
0
10
VUS
3
92
7
0
102
Likely Benign
0
2
3
19
24
Benign
0
1
4
4
9
Conflicting
7
Total3993323165

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

View in ClinVar →

Protein Context — Lollipop Plot

MITD1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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