MYRF

Chr 11

myelin regulatory factor

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

NCBI Gene: 745 ENSG00000124920 UniProt: Q9Y2G1

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.

GeneReviews 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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEncephalitis/encephalopathy, mild, with reversible myelin vacuolization

UniProtCardiac-urogenital syndrome

UniProtNanophthalmos 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · cardiac-urogenital syndrome · AD · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.12

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — MYRF

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in MYRF?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

1,203 rare PASS variants

Rare truncating (LoF)

1 in 1,400

84 rare PASS variants

Rare synonymous (reference)

1 in 47

656 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MYRF. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 54	1 in 1,400
South Asian	~43k	1 in 44	1 in 1,400
Remaining (unassigned)	~30k	1 in 43	1 in 2,200
European (Finnish)	~27k	1 in 130	1 in 550
Admixed American	~22k	1 in 41	1 in 3,600
African / African American	~21k	1 in 50	1 in 1,500
East Asian	~20k	1 in 44	≈ 1 in 6,400
Ashkenazi Jewish	~13k	1 in 200	1 in 1,700
Middle Eastern	~2,884	1 in 39	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 25 of 27 coding exons well covered in gnomAD exomes; exons 1, 16 marginal. Genomes: all 27.? see exons ↓