MROH9

Chr 1

maestro heat like repeat family member 9

Also known as: ARMC11, C1orf129

NCBI Gene: 80133 ENSG00000117501 UniProt: Q5TGP6

This gene encodes a protein of unknown function that is not highly constrained against loss-of-function variants. Biallelic mutations in MROH9 cause autosomal recessive intellectual disability with seizures and brain abnormalities including cerebellar hypoplasia. The phenotype typically presents in early childhood with developmental delays and epilepsy.

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.98

Clinical Summary— MROH9

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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

71 VUS of 90 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?

0.98LOEUF

pLI 0.000

Z-score 1.66

OE 0.72 (0.54–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.92–1.08)

420 obs / 420.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.54–0.98)

0≤0.351.4

Missense OE?1.00 (0.92–1.08)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 30 / 41.5Missense obs/exp: 420 / 420.6Syn Z: -0.40

This gene — mechanism propensity

0.7228th %ile

GOF

0.6541th %ile

LOF

0.2385th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

90 submitted variants in ClinVar

ClinVar

Classification Summary

VUS71

Likely Benign13

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	71	0	71
Likely Benign	10	3	13
Benign	0	0	0
Total	81	3	84

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap MROH9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →