PPP1R12A

Chr 12

protein phosphatase 1 regulatory subunit 12A

Also known as: GUBS, M130, MBS, MYPT1

NCBI Gene: 4659ENSG00000058272UniProt: O14974

Myosin phosphatase target subunit 1, which is also called the myosin-binding subunit of myosin phosphatase, is one of the subunits of myosin phosphatase. Myosin phosphatase regulates the interaction of actin and myosin downstream of the guanosine triphosphatase Rho. The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle and interaction of actin and myosin in nonmuscle cells. The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP.RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC. Rho-associated kinase (Rho-kinase), which is activated by GTP. RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGenitourinary and/or brain malformation syndrome

Clinical highlights

Gene-disease validity (ClinGen)
genitourinary and/or brain malformation syndrome · ADStrongappropriate for clinical testing
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.
0
Active trials
15
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — PPP1R12A
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.13LOEUF
pLI 1.000
Z-score 6.81
OE 0.05 (0.02–0.13)
Highly constrained

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

Missense Constraint?
2.64Z-score
OE missense 0.67 (0.61–0.73)
342 obs / 509.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.05 (0.02–0.13)
0≤0.351.4
Missense OE?0.67 (0.61–0.73)
0≤0.61.4
Synonymous OE?0.98
0≤1.21.6
LoF obs/exp: 3 / 59.8Missense obs/exp: 342 / 509.5Syn Z: 0.19

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients