MROH1

Chr 8

maestro heat like repeat family member 1

Also known as: HEATR7A

NCBI Gene: 727957 ENSG00000179832 UniProt: Q8NDA8

MROH1 encodes a lysosome fission factor that mediates the constriction and scission of lysosomal tubules by homooligomerizing at scission sites, which is essential for maintaining lysosome number, shape, size, and function. The gene is highly constrained against loss-of-function variants (LOEUF 0.486), suggesting that mutations would likely cause severe disease, though specific associated disorders have not yet been established in the literature. Given the critical role of lysosomes in cellular function, mutations would be expected to follow an autosomal recessive inheritance pattern and potentially affect multiple organ systems.

ResearchSummary from RefSeq, UniProt

Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.49

Clinical Summary— MROH1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

62 VUS of 92 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.203

Z-score 3.45

OE 0.25 (0.13–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.60Z-score

OE missense 0.90 (0.81–1.00)

252 obs / 280.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.13–0.49)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 6 / 24.3Missense obs/exp: 252 / 280.2Syn Z: -0.86

This gene — mechanism propensity

0.6552th %ile

GOF

0.6151th %ile

LOF

0.3261th %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

92 submitted variants in ClinVar

ClinVar

Classification Summary

VUS62

Likely Benign11

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	62	0	62
Likely Benign	10	1	11
Benign	0	0	0
Total	72	1	73

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

View in ClinVar →

59 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap MROH1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →