MAU2

Chr 19AD

MAU2 sister chromatid cohesion factor

Also known as: CDLS7, KIAA0892, MAU2L, SCC4, mau-2

NCBI Gene: 23383 ENSG00000129933 UniProt: Q9Y6X3 OMIM: 614560

The MAU2 protein forms a complex with NIPBL to load cohesin onto chromatin, which is essential for sister chromatid cohesion during cell division. Mutations cause an autosomal recessive neurodevelopmental disorder characterized by intellectual disability, seizures, and distinctive facial features. This gene is highly constrained against loss-of-function variants, indicating critical importance for normal cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Enables cohesin loader activity. Involved in maintenance of mitotic sister chromatid cohesion. Located in chromatin and nuclear body. Part of Scc2-Scc4 cohesin loading complex. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cornelia de Lange syndrome 7MIM #621570

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cornelia de Lange syndrome 7; no ClinGen or GenCC tier

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 — MAU2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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 5.70

OE 0.03 (0.01–0.12)

Highly constrained

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

Missense Constraint?

4.03Z-score

OE missense 0.41 (0.36–0.47)

150 obs / 367.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.12)

0≤0.351.4

Missense OE?0.41 (0.36–0.47)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 1 / 39.8Missense obs/exp: 150 / 367.7Syn Z: -1.48

Background carrier burden — how many people carry a rare variant somewhere in MAU2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

461 rare PASS variants

Rare truncating (LoF)

1 in 13,000

19 rare PASS variants

Rare synonymous (reference)

1 in 150

387 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAU2. 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 390	1 in 50,000
South Asian	~43k	1 in 220	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 260	none seen
European (Finnish)	~27k	1 in 430	1 in 3,300
Admixed American	~22k	1 in 250	none seen
African / African American	~21k	1 in 200	≈ 1 in 6,900
East Asian	~20k	1 in 240	none seen
Ashkenazi Jewish	~13k	1 in 440	none seen
Middle Eastern	~2,884	≈ 1 in 850	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 19 coding exons well covered in gnomAD exomes and genomes.? see exons ↓