MRTFB

Chr 16

myocardin related transcription factor B

Also known as: MKL2, MRTF-B, NPD001

NCBI Gene: 57496 ENSG00000186260 OMIM: 609463

The MRTFB protein acts as a transcriptional coactivator of serum response factor (SRF) and is required for skeletal myogenic differentiation. Mutations cause autosomal dominant developmental and epileptic encephalopathy, affecting neurological development and muscle function. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.17), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables transcription coactivator activity. Involved in positive regulation of miRNA transcription; positive regulation of striated muscle tissue development; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in several cellular components, including glutamatergic synapse; postsynapse; and presynapse. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.17

Clinical Summary— MRTFB

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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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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 151 VUS of 182 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 5.85

OE 0.07 (0.03–0.17)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.52Z-score

OE missense 0.94 (0.88–1.01)

548 obs / 583.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.17)

0≤0.351.4

Missense OE?0.94 (0.88–1.01)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 3 / 45.6Missense obs/exp: 548 / 583.6Syn Z: -1.40

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedMRTFB-related neurodevelopmental disorderGOFAD

This gene — mechanism propensity

0.3097th %ile

GOF

0.2597th %ile

LOF

0.75top 10%

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

LOFprediction above median · LOEUF 0.17

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

182 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS151

Likely Benign14

Benign4

Pathogenic

151

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	2	1	3
Likely Pathogenic	0	0	0	0
VUS	1	149	1	151
Likely Benign	0	9	5	14
Benign	0	2	2	4
Total	1	162	9	172

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap MRTFB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →