MROH6

Chr 8

maestro heat like repeat family member 6

Also known as: C8orf73

NCBI Gene: 642475 ENSG00000204839 UniProt: A6NGR9

The MROH6 protein is predicted to be active in the cytoplasm, but its specific cellular function remains unclear. Mutations in this gene have been associated with neurodevelopmental disorders, though the clinical phenotype and inheritance pattern are not well-established from current data. This gene appears to tolerate loss-of-function variants well based on constraint metrics.

ResearchSummary from RefSeq

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

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.35

Clinical Summary— MROH6

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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

200 VUS of 239 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?

1.35LOEUF

pLI 0.000

Z-score 0.09

OE 0.98 (0.72–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.66Z-score

OE missense 1.10 (1.01–1.19)

402 obs / 366.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.98 (0.72–1.35)

0≤0.351.4

Missense OE?1.10 (1.01–1.19)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 27 / 27.5Missense obs/exp: 402 / 366.4Syn Z: -1.56

This gene — mechanism propensity

0.6065th %ile

GOF

0.7127th %ile

LOF

0.3453th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

239 submitted variants in ClinVar

ClinVar

Classification Summary

VUS200

Likely Benign15

200

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	200	0	200
Likely Benign	14	1	15
Benign	0	0	0
Total	214	1	215

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

View in ClinVar →

60 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap MROH6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →