PPP1R12A

Chr 12AD

protein phosphatase 1 regulatory subunit 12A

Also known as: GUBS, M130, MBS, MYPT1

Myosin phosphatase target subunit 1 is a key regulator of protein phosphatase 1C that mediates binding to myosin and regulates actin-myosin interactions in smooth muscle contraction and nonmuscle cells. Mutations cause genitourinary and/or brain malformation syndrome with autosomal dominant inheritance. This gene is extremely constrained against loss-of-function variants (pLI >0.99, LOEUF 0.13), indicating that such mutations are likely to have severe effects.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.131 OMIM phenotype
Clinical SummaryPPP1R12A
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Gene-Disease Validity (ClinGen)
genitourinary and/or brain malformation syndrome · ADStrong

Strong evidence — appropriate for clinical testing

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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GeneReview available — PPP1R12A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 6.81
OE 0.05 (0.020.13)
Highly constrained

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

Missense Constraint
2.64Z-score
OE missense 0.67 (0.610.73)
342 obs / 509.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.13)
00.351.4
Missense OE0.67 (0.610.73)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 3 / 59.8Missense obs/exp: 342 / 509.5Syn Z: 0.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPPP1R12A-related holoprosencephaly spectrum and urogenital malformationsLOFAD
DN
0.3495th %ile
GOF
0.4085th %ile
LOF
0.82top 5%

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

LOFprediction above median · LOEUF 0.13

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PPP1R12A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC