PPP1R16A

Chr 8

protein phosphatase 1 regulatory subunit 16A

NCBI Gene: 84988 ENSG00000160972 UniProt: Q96I34 OMIM: 609172

The protein functions as a myosin phosphatase targeting subunit that directs protein phosphatase 1 to specific substrates including myosin light chains, regulating muscle contraction and intracellular movement. Mutations in PPP1R16A cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint to loss-of-function variation, suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Inhibits protein phosphatase 1 activity toward phosphorylase, myosin light chain and myosin substrates

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.004

Z-score 2.81

OE 0.36 (0.21–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.89–1.07)

320 obs / 326.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.65)

0≤0.351.4

Missense OE?0.98 (0.89–1.07)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 8 / 22.3Missense obs/exp: 320 / 326.5Syn Z: -2.97

Background carrier burden — how many people carry a rare variant somewhere in PPP1R16A?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

848 rare PASS variants

Rare truncating (LoF)

1 in 1,200

116 rare PASS variants

Rare synonymous (reference)

1 in 65

436 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PPP1R16A. 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 86	1 in 1,700
South Asian	~43k	1 in 85	1 in 1,800
Remaining (unassigned)	~30k	1 in 58	1 in 730
European (Finnish)	~26k	1 in 170	1 in 1,400
Admixed American	~22k	1 in 66	1 in 3,200
African / African American	~21k	1 in 59	1 in 3,000
East Asian	~20k	1 in 86	1 in 1,600
Ashkenazi Jewish	~13k	1 in 300	1 in 2,600
Middle Eastern	~2,884	1 in 61	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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓