MARCHF10

Chr 17

membrane associated ring-CH-type finger 10

Also known as: MARCH-X, MARCH10, RNF190

NCBI Gene: 162333ENSG00000173838UniProt: Q8NA82

MARCHF10 encodes a membrane-bound E3 ubiquitin ligase that transfers ubiquitin to substrate proteins to regulate vesicular transport between cellular membrane compartments. Mutations cause disease through a dominant-negative mechanism, though specific clinical phenotypes associated with MARCHF10 variants have not been clearly established. The gene shows tolerance to loss-of-function variants, suggesting haploinsufficiency may not be the primary disease mechanism.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
0
Pubs (1 yr)
12
P/LP submissions
0%
P/LP missense
1.39
LOEUF
DN
Mechanism· predicted
Clinical Summary— MARCHF10
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 100 VUS of 161 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.39LOEUF
pLI 0.000
Z-score -0.27
OE 1.05 (0.80–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.70Z-score
OE missense 0.90 (0.83–0.98)
374 obs / 414.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.05 (0.80–1.39)
0≤0.351.4
Missense OE0.90 (0.83–0.98)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 35 / 33.3Missense obs/exp: 374 / 414.2Syn Z: -0.76
DN
0.7034th %ile
GOF
0.5170th %ile
LOF
0.3746th %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

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic2
VUS100
Likely Benign22
Benign17
10
Pathogenic
2
Likely Pathogenic
100
VUS
22
Likely Benign
17
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
2
0
2
VUS
0
97
3
0
100
Likely Benign
0
15
2
5
22
Benign
1
9
1
6
17
Total11211811151

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

View in ClinVar →

Protein Context — Lollipop Plot

MARCHF10 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients