MORF4L2

Chr X

mortality factor 4 like 2

Also known as: MORFL2, MRGX

NCBI Gene: 9643 ENSG00000123562 UniProt: Q15014

The protein is a component of the NuA4 histone acetyltransferase complex that regulates gene transcription through chromatin modification and participates in DNA double-strand break repair via homologous recombination. Mutations cause autosomal dominant neurodevelopmental disorder with variable intellectual disability, behavioral abnormalities, and dysmorphic features. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

ResearchSummary from RefSeq, UniProt

Involved in positive regulation of double-strand break repair via homologous recombination and regulation of cell cycle. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.54

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.811

Z-score 2.17

OE 0.00 (0.00–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.76Z-score

OE missense 0.52 (0.42–0.65)

56 obs / 107.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.54)

0≤0.351.4

Missense OE?0.52 (0.42–0.65)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 0 / 5.5Missense obs/exp: 56 / 107.5Syn Z: 0.70

Background carrier burden — how many people carry a rare variant somewhere in MORF4L2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 850

135 rare PASS variants

Rare truncating (LoF)

1 in 370,000

2 rare PASS variants

Rare synonymous (reference)

1 in 1,300

75 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MORF4L2. 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)	~561k	1 in 860	none seen
South Asian	~36k	1 in 2,000	none seen
Remaining (unassigned)	~31k	1 in 850	≈ 1 in 31,000
European (Finnish)	~27k	1 in 1,700	none seen
Admixed American	~23k	1 in 690	≈ 1 in 23,000
African / African American	~21k	1 in 790	none seen
East Asian	~20k	1 in 610	none seen
Ashkenazi Jewish	~13k	1 in 720	none seen
Middle Eastern	~2,758	≈ 1 in 1,400	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): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓