MYRF

Chr 11AD

myelin regulatory factor

Also known as: 11orf9, C11orf9, CUGS, MMERV, MRF, NNO1, Ndt80, pqn-47

NCBI Gene: 745 ENSG00000124920 UniProt: Q9Y2G1 OMIM: 608329

This gene encodes a transcription factor that regulates central nervous system myelination by activating myelin gene expression and promoting oligodendrocyte differentiation. Mutations cause autosomal dominant cardiac-urogenital syndrome, mild encephalitis/encephalopathy with reversible myelin vacuolization, and nanophthalmos. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.12), reflecting its essential role in normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transcription factor that is required for central nervous system myelination and may regulate oligodendrocyte differentiation. It is thought to act by increasing the expression of genes that effect myelin production but may also directly promote myelin gene expression. Loss of a similar gene in mouse models results in severe demyelination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.123 OMIM phenotypes

Clinical Summary— MYRF

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Gene-Disease Validity (ClinGen)

cardiac-urogenital syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 6.55

OE 0.04 (0.01–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.29Z-score

OE missense 0.65 (0.60–0.70)

456 obs / 701.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.12)

0≤0.351.4

Missense OE?0.65 (0.60–0.70)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 2 / 53.9Missense obs/exp: 456 / 701.4Syn Z: 1.16

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongMYRF-related pulmonary artery and lung hypoplasia, agonadism, omphalocele, diaphragmatic defects, hypoplastic left heart, and scimitar syndromeLOFAD

strongMYRF-related high hyperopiaOTHERAD

This gene — mechanism propensity

0.3892th %ile

GOF

0.2995th %ile

LOF

0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.12

Literature Evidence

LOFReview of the phenotypic spectrum associated with haploinsufficiency of MYRF.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References