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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP1R12A
protein phosphatase 1 regulatory subunit 12A
Chromosome 12 · 12q21.2-q21.31
NCBI Gene: 4659Ensembl: ENSG00000058272.20HGNC: HGNC:7618UniProt: B2RAH5
248PubMed Papers
21Diseases
0Drugs
34Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
contractile muscle fiberactin cytoskeletoncentrosomecytosolgenitourinary and/or brain malformation syndromeneurodegenerative diseasegenetic disorderAlzheimer disease
✦AI Summary

PPP1R12A encodes myosin light chain phosphatase target subunit 1 (MYPT1), a key regulatory component of the myosin phosphatase complex that dephosphorylates myosin light chains and other substrates 1. As a regulatory subunit of protein phosphatase 1 (PP1), PPP1R12A mediates PP1 binding to myosin and participates in dephosphorylation of multiple targets including PLK1 and MKLP1/KIF23 during cytokinesis 2. The gene undergoes complex alternative splicing producing 11 protein-coding transcripts with tissue-specific expression patterns; endothelial and smooth muscle cells predominantly express full-length variants, while platelets favor E14-skipped isoforms 1. PPP1R12A localizes to recycling endosomes where it facilitates YAP dephosphorylation and activation, promoting cancer cell proliferation 3. Disease associations include persistent Müllerian duct syndrome (PMDS), caused by truncation mutations disrupting Müllerian regression independently of AMH signaling 4, and genitourinary/brain malformation syndrome (GUBS) from haploinsufficiency 5. Variants are associated with hypertensive disorders of pregnancy susceptibility 6 and altered vascular smooth muscle cell contractility in abdominal aortic aneurysm 7. A circular RNA derivative, circPPP1R12A, encodes a functional 73-amino acid protein that promotes colorectal cancer progression via Hippo-YAP pathway activation 8.

Sources cited
1
PPP1R12A encodes MYPT1, a key component of myosin light chain phosphatase complex; undergoes alternative splicing producing 11 protein-coding transcripts with tissue-specific patterns
PMID: 35954160
2
PP1β-MYPT1 phosphatase dephosphorylates MKLP1/KIF23 during cytokinesis and regulates microtubule dynamics in late cytokinesis
PMID: 31586073
3
PPP1R12A localizes to recycling endosomes and facilitates YAP dephosphorylation and activation; high expression correlates with poor breast cancer prognosis
PMID: 37957190
4
PPP1R12A truncation mutations cause persistent Müllerian duct syndrome in 21% of patients lacking AMH/AMHR2 mutations; myosin phosphatase involvement in Müllerian regression is independent of AMH signaling
PMID: 36331510
5
PPP1R12A non-coding variant c.2666+3A>G causes genitourinary/brain malformation syndrome through haploinsufficiency and abnormal splicing producing truncated protein
PMID: 37272772
6
PPP1R12A gene variants are associated with susceptibility to superimposed preeclampsia in hypertensive disorders of pregnancy
PMID: 33459569
7
PPP1R12A shows altered phosphorylation in vascular smooth muscle cells from abdominal aortic aneurysm patients, affecting contractility-related processes
PMID: 39206541
8
Circular RNA circPPP1R12A encodes a functional 73-amino acid protein that promotes colorectal cancer proliferation and metastasis via Hippo-YAP pathway activation
PMID: 30925892
Disease Associationsⓘ21
genitourinary and/or brain malformation syndromeOpen Targets
0.77Strong
neurodegenerative diseaseOpen Targets
0.57Moderate
genetic disorderOpen Targets
0.41Moderate
Alzheimer diseaseOpen Targets
0.35Weak
lysosomal storage diseaseOpen Targets
0.34Weak
multiple sclerosisOpen Targets
0.34Weak
Parkinson diseaseOpen Targets
0.34Weak
head and neck malignant neoplasiaOpen Targets
0.27Weak
inherited hemoglobinopathyOpen Targets
0.26Weak
posterior cortical atrophyOpen Targets
0.10Weak
neoplasmOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
Ehlers-Danlos syndromeOpen Targets
0.07Suggestive
Ischemic strokeOpen Targets
0.06Suggestive
Churg-Strauss syndromeOpen Targets
0.05Suggestive
necrotizing enterocolitisOpen Targets
0.04Suggestive
skin diseaseOpen Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.04Suggestive
Genitourinary and/or brain malformation syndromeUniProt
Pathogenic Variants34
NM_002480.3(PPP1R12A):c.1510C>T (p.Arg504Ter)Pathogenic
Genitourinary and/or brain malformation syndrome
★★☆☆2024→ Residue 504
NM_002480.3(PPP1R12A):c.2698C>T (p.Arg900Ter)Pathogenic
Genitourinary and/or brain malformation syndrome|not provided
★★☆☆2023→ Residue 900
NM_002480.3(PPP1R12A):c.957-2A>CPathogenic
Differences in sex development
★☆☆☆2025
NM_002480.3(PPP1R12A):c.2650-2A>TLikely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2025
NM_002480.3(PPP1R12A):c.1324_1327del (p.Lys442fs)Likely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2025→ Residue 442
NM_002480.3(PPP1R12A):c.2759dup (p.Tyr920Ter)Likely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2025→ Residue 920
NM_002480.3(PPP1R12A):c.652_653del (p.Leu218fs)Pathogenic
not provided
★☆☆☆2025→ Residue 218
NM_002480.3(PPP1R12A):c.1333del (p.Ser445fs)Pathogenic
Inborn genetic diseases
★☆☆☆2024→ Residue 445
NM_002480.3(PPP1R12A):c.737A>C (p.Glu246Ala)Likely pathogenic
not provided
★☆☆☆2024→ Residue 246
NM_002480.3(PPP1R12A):c.38A>G (p.Gln13Arg)Likely pathogenic
not provided
★☆☆☆2024→ Residue 13
NM_002480.3(PPP1R12A):c.3046G>A (p.Asp1016Asn)Likely pathogenic
not provided
★☆☆☆2024→ Residue 1016
NM_002480.3(PPP1R12A):c.329T>A (p.Leu110Gln)Likely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2024→ Residue 110
NM_002480.3(PPP1R12A):c.522_523dup (p.Arg175fs)Likely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2024→ Residue 175
NM_002480.3(PPP1R12A):c.2152C>T (p.Arg718Ter)Likely pathogenic
not provided
★☆☆☆2023→ Residue 718
NM_002480.3(PPP1R12A):c.2533C>T (p.Arg845Ter)Pathogenic
PPP1R12A-related disorder|Genitourinary and/or brain malformation syndrome
★☆☆☆2023→ Residue 845
NM_002480.3(PPP1R12A):c.2604del (p.Glu868fs)Pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2023→ Residue 868
NM_002480.3(PPP1R12A):c.647+2T>GLikely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2022
NM_002480.3(PPP1R12A):c.127del (p.Val43fs)Likely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2022→ Residue 43
NM_002480.3(PPP1R12A):c.1567C>T (p.Arg523Ter)Likely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2021→ Residue 523
NM_002480.3(PPP1R12A):c.2801del (p.Lys934fs)Likely pathogenic
Genitourinary and/or brain malformation syndrome
★☆☆☆2021→ Residue 934
View on ClinVar ↗
Related Genes
MYL12BProtein interaction100%TOX4Protein interaction100%CDK1Protein interaction99%MYL9Protein interaction99%MYL12AProtein interaction99%RHOCProtein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
62%
Heart
52%
Ovary
49%
Brain
46%
Liver
21%
Gene Interaction Network
Click a node to explore
PPP1R12AMYL12BTOX4CDK1MYL9MYL12ARHOC
PROTEIN STRUCTURE
Preparing viewer…
PDB2KJY · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.16Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.08 [0.05–0.16]
RankingsWhere PPP1R12A stands among ~20K protein-coding genes
  • #1,558of 20,598
    Most Researched248 · top 10%
  • #1,689of 5,498
    Most Pathogenic Variants34
  • #240of 17,882
    Most Constrained (LOEUF)0.16 · top 5%
Genes detectedPPP1R12A
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
PMID: 20301702
1.00
2
Complex Transcriptional Profiles of the
PMID: 35954160
Cells · 2022
0.90
3
Molecular mechanism of bitter taste receptor agonist-mediated relaxation of airway smooth muscle.
PMID: 39037554
FASEB J · 2024
0.80
4
The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis.
PMID: 31586073
Nat Commun · 2019
0.80
5
Haplotype-based, case-control study of myosin phosphatase target subunit 1 (
PMID: 33459569
Hypertens Pregnancy · 2021
0.70