PPP1R16A

Summary

PPP1R16A (protein phosphatase 1 regulatory subunit 16A, HGNC:14941) is a protein-coding gene on chromosome 8q24.3, encoding Protein phosphatase 1 regulatory subunit 16A (Q96I34). Inhibits protein phosphatase 1 activity toward phosphorylase, myosin light chain and myosin substrates.

Myosin light chain kinase and phosphatase (MLCP) complexes control the phosphorylation states of regulatory myosin light chains, which is crucial for muscle and intracellular movement. MLCPs typically contain a catalytic protein phosphatase 1 (PP1c) subunit, a myosin phosphatase targeting (MYPT) subunit, and another smaller subunit. The protein encoded by this gene represents an MYPT subunit, which is responsible for directing PP1c to its intended targets. However, while the phosphorylation of other MYPT members results in PP1c inactivation, phosphorylation of the encoded protein by protein kinase A results in PP1c activation.

Source: NCBI Gene 84988 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_001329443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14941
Approved symbol	PPP1R16A
Name	protein phosphatase 1 regulatory subunit 16A
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC14333, MYPT3
Ensembl gene	ENSG00000160972
Ensembl biotype	protein_coding
OMIM	609172
Entrez	84988

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 39 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000292539, ENST00000435887, ENST00000526183, ENST00000526564, ENST00000526643, ENST00000528430, ENST00000529009, ENST00000529283, ENST00000532806, ENST00000533088, ENST00000533829, ENST00000909503, ENST00000909504, ENST00000909505, ENST00000909506, ENST00000909507, ENST00000909508, ENST00000909509, ENST00000909510, ENST00000909511, ENST00000909512, ENST00000909513, ENST00000909514, ENST00000909515, ENST00000909516, ENST00000909517, ENST00000909518, ENST00000909519, ENST00000909520, ENST00000909521, ENST00000909522, ENST00000909523, ENST00000909524, ENST00000909525, ENST00000909526, ENST00000909527, ENST00000920082, ENST00000920083, ENST00000920084, ENST00000920085, ENST00000920086, ENST00000920087, ENST00000920088, ENST00000963334, ENST00000963335, ENST00000963336, ENST00000963337

RefSeq mRNA: 5 — MANE Select: NM_001329443 NM_001329442, NM_001329443, NM_001329444, NM_001329445, NM_032902

CCDS: CCDS6429

Canonical transcript exons

ENST00000435887 — 12 exons

Exon	Start	End
ENSE00001055766	144500267	144500391
ENSE00001473528	144496461	144497453
ENSE00002168736	144490034	144490212
ENSE00002179155	144501520	144502121
ENSE00003480107	144498916	144499061
ENSE00003484781	144500487	144500612
ENSE00003522679	144500096	144500199
ENSE00003539415	144500686	144500761
ENSE00003540187	144501129	144501294
ENSE00003627281	144498770	144498840
ENSE00003638614	144500842	144500971
ENSE00003919775	144477982	144478127

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2458 / max 236.6165, expressed in 1767 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91514	6.5451	1720
91519	3.7049	675
91515	1.0693	613
91520	0.6566	193
91521	0.1464	64
91516	0.1185	67
91518	0.0051	3

Top tissues by expression

254 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.79	gold quality
right uterine tube	UBERON:0001302	98.41	gold quality
mucosa of transverse colon	UBERON:0004991	98.04	gold quality
right lobe of liver	UBERON:0001114	97.03	gold quality
left ventricle myocardium	UBERON:0006566	96.99	gold quality
adenohypophysis	UBERON:0002196	96.86	gold quality
right testis	UBERON:0004534	96.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.48	gold quality
left testis	UBERON:0004533	96.41	gold quality
duodenum	UBERON:0002114	96.35	gold quality
heart left ventricle	UBERON:0002084	96.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.19	gold quality
cardiac ventricle	UBERON:0002082	96.10	gold quality
pituitary gland	UBERON:0000007	96.05	gold quality
body of pancreas	UBERON:0001150	96.03	gold quality
cortex of kidney	UBERON:0001225	95.99	gold quality
metanephros cortex	UBERON:0010533	95.88	gold quality
lower esophagus mucosa	UBERON:0035834	95.51	gold quality
right atrium auricular region	UBERON:0006631	95.19	gold quality
transverse colon	UBERON:0001157	95.05	gold quality
body of stomach	UBERON:0001161	94.98	gold quality
right adrenal gland	UBERON:0001233	94.98	gold quality
right lobe of thyroid gland	UBERON:0001119	94.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.87	gold quality
right adrenal gland cortex	UBERON:0035827	94.72	gold quality
kidney epithelium	UBERON:0004819	94.70	gold quality
left adrenal gland cortex	UBERON:0035825	94.70	gold quality
cardiac atrium	UBERON:0002081	94.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.64	gold quality
adult mammalian kidney	UBERON:0000082	94.62	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	428.13
E-HCAD-10	yes	33.99
E-GEOD-125970	yes	15.08
E-ANND-3	yes	10.11
E-MTAB-6524	no	47.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting PPP1R16A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-4256	96.22	67.70	669
HSA-MIR-11181-5P	96.12	67.46	665

Literature-anchored findings (GeneRIF, showing 2)

• analysis of a novel mechanism for the phosphorylation of MYPT3 by PKA and activation of the catalytic activity through direct interaction of a central region of MYPT3 with its N-terminal region (PMID:16920702)
• PPP1R16A gene expression is decreased in follicular variant of papillary thyroid carcinoma. (PMID:21509594)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r16a	ENSDARG00000076980
mus_musculus	Ppp1r16a	ENSMUSG00000033819
rattus_norvegicus	Ppp1r16a	ENSRNOG00000015450
drosophila_melanogaster	MYPT-75D	FBGN0036801
caenorhabditis_elegans	gfi-2	WBGENE00001582

Paralogs (1): PPP1R16B (ENSG00000101445)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 16A — Q96I34 (reviewed: Q96I34)

Alternative names: Myosin phosphatase-targeting subunit 3

All UniProt accessions (2): Q96I34, A0A087WWZ0

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Binds PP1.

Subcellular location. Cell membrane.

RefSeq proteins (5): NP_001316371, NP_001316372, NP_001316373, NP_001316374, NP_116291 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR017417	Pase-1_reg_su_16AB	Family
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR051226	PP1_Regulatory_Subunit	Family

Pfam: PF12796

UniProt features (20 total): repeat 5, region of interest 4, sequence conflict 3, modified residue 2, lipid moiety-binding region 2, chain 1, propeptide 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96I34-F1	72.64	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 433, 525, 524, 525

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, LFA1_Q6, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, CHX10_01, GATA1_03, ACEVEDO_LIVER_CANCER_UP, TAATTA_CHX10_01, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_PHOSPHATASE_REGULATOR_ACTIVITY, ER_Q6_01, FEVR_CTNNB1_TARGETS_UP

GO Biological Process (0):

GO Molecular Function (4): enzyme inhibitor activity (GO:0004857), myosin phosphatase regulator activity (GO:0017020), protein binding (GO:0005515), protein phosphatase regulator activity (GO:0019888)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
catalytic activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1
myosin phosphatase activity	1
protein phosphatase regulator activity	1
binding	1
phosphoprotein phosphatase activity	1
phosphatase regulator activity	1
protein phosphatase binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R16A	HSP90AA1	P07900	749
PPP1R16A	HSP90AB1	P08238	749
PPP1R16A	PPP1CB	P37140	748
PPP1R16A	PPP1CC	P36873	694
PPP1R16A	TMEM276	P0DTL5	630
PPP1R16A	LRRC14	Q15048	588
PPP1R16A	MROH1	Q8NDA8	581
PPP1R16A	REX1BD	Q96EN9	545
PPP1R16A	LRRC24	Q50LG9	475
PPP1R16A	CPSF1	Q10570	465
PPP1R16A	ARHGAP39	Q9C0H5	461
PPP1R16A	SLC33A2	Q96ES6	460
PPP1R16A	ADCK5	Q3MIX3	456
PPP1R16A	GRINA	Q7Z429	451
PPP1R16A	OAZ3	Q9UMX2	433

IntAct

170 interactions, top by confidence:

A	B	Type	Score
PPP1R16A	PPP1CB	psi-mi:“MI:0915”(physical association)	0.830
PPP1CB	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.830
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1R16A	TPP2	psi-mi:“MI:0915”(physical association)	0.670
TPP2	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.670
TRIP6	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.620
PPP1R16A	TLE5	psi-mi:“MI:0915”(physical association)	0.560
TLE5	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
PPP1R16A	ANTKMT	psi-mi:“MI:0915”(physical association)	0.560
HDAC7	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
PPP1R16A	MCCD1	psi-mi:“MI:0915”(physical association)	0.560
	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
PPP1R16A	TSSK3	psi-mi:“MI:0915”(physical association)	0.560
PPP1R16A	SCNM1	psi-mi:“MI:0915”(physical association)	0.560
CDCA7L	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
PPP1CC	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
CCDC116	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
SUV39H1	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	PPP1R16A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (69): PPP1R16A (Two-hybrid), PPP1R16A (Two-hybrid), PPP1R16A (Two-hybrid), PPP1R16A (Two-hybrid), PPP1R16A (Affinity Capture-MS), PPP1R16A (Two-hybrid), PPP1R16A (Two-hybrid), PPP1R16A (Two-hybrid), PPP1R16A (Two-hybrid), PPP1R16A (Affinity Capture-MS), PPP1R16A (Affinity Capture-MS), PPP1R16A (Affinity Capture-MS), PPP1R16A (Affinity Capture-MS), PPP1R16A (Two-hybrid), PPP1R16A (Two-hybrid)

ESM2 similar proteins: A5PK26, F8VPU2, O14526, O14976, O15068, O75064, O94887, P00530, P97874, P98150, P98171, Q00653, Q15027, Q15149, Q2HJE1, Q2KHV6, Q3TBD2, Q3U1Y4, Q4LDD4, Q5FVC7, Q5RB40, Q5RC07, Q5U464, Q5ZK62, Q61210, Q64096, Q6DE55, Q6IVG4, Q6P730, Q6ZQK5, Q6ZSZ5, Q8CFD4, Q8K285, Q8K2H4, Q8R5G7, Q8TDY4, Q8WWN8, Q91VS8, Q91ZR2, Q92619

Diamond homologs: A2AQH4, O14974, O60237, Q10728, Q3UMT1, Q6DRG7, Q8BG95, Q90623, Q923M0, Q96I34, Q9BZL4, Q9DBR7, Q8VHQ3, Q95N27, Q96T49, A4II29, B2RR83, G3I6Z6, O00522, O13987, P46531, P83757, Q01705, Q02979, Q03017, Q07008, Q0VC93, Q18297, Q1RJ94, Q28FJ2, Q337A0, Q3SX00, Q3UES3, Q3V096, Q4FE45, Q4JHE0, Q5H9F3, Q5I1X5, Q5R746, Q5R8C8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

99 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2133 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144498768:A:AG	acceptor_gain	1.0000
8:144498769:G:GA	acceptor_gain	1.0000
8:144498769:GTCC:G	acceptor_gain	1.0000
8:144498836:ACCAG:A	donor_loss	1.0000
8:144498837:CCAG:C	donor_loss	1.0000
8:144498838:CAG:C	donor_loss	1.0000
8:144498839:AG:A	donor_loss	1.0000
8:144498840:GG:G	donor_loss	1.0000
8:144498841:G:A	donor_loss	1.0000
8:144498914:A:AG	acceptor_gain	1.0000
8:144498915:G:GG	acceptor_gain	1.0000
8:144498915:GT:G	acceptor_gain	1.0000
8:144498915:GTGC:G	acceptor_gain	1.0000
8:144498915:GTGCT:G	acceptor_gain	1.0000
8:144499058:CCAGG:C	donor_loss	1.0000
8:144499059:CAG:C	donor_loss	1.0000
8:144499061:GGT:G	donor_loss	1.0000
8:144499063:T:G	donor_loss	1.0000
8:144500093:CAG:C	acceptor_loss	1.0000
8:144500094:A:AG	acceptor_gain	1.0000
8:144500094:AGT:A	acceptor_gain	1.0000
8:144500094:AGTG:A	acceptor_gain	1.0000
8:144500095:G:GC	acceptor_gain	1.0000
8:144500095:GT:G	acceptor_gain	1.0000
8:144500095:GTG:G	acceptor_gain	1.0000
8:144500095:GTGG:G	acceptor_gain	1.0000
8:144500095:GTGGC:G	acceptor_gain	1.0000
8:144500197:GTG:G	donor_gain	1.0000
8:144500388:GCTG:G	donor_gain	1.0000
8:144500390:TGGTG:T	donor_loss	1.0000

AlphaMissense

3427 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144500137:C:A	P173H	0.999
8:144498921:C:G	C112W	0.998
8:144498997:T:A	W138R	0.998
8:144498997:T:C	W138R	0.998
8:144499019:C:A	A145D	0.998
8:144500120:C:A	N167K	0.998
8:144500120:C:G	N167K	0.998
8:144498999:G:C	W138C	0.997
8:144498999:G:T	W138C	0.997
8:144499018:G:C	A145P	0.997
8:144500119:A:T	N167I	0.997
8:144500150:T:G	C177W	0.997
8:144498920:G:A	C112Y	0.996
8:144499004:C:A	P140H	0.996
8:144499016:C:A	A144E	0.996
8:144500118:A:T	N167Y	0.996
8:144500137:C:G	P173R	0.996
8:144500149:G:A	C177Y	0.996
8:144500577:T:A	W266R	0.996
8:144500577:T:C	W266R	0.996
8:144498986:A:T	D134V	0.995
8:144499015:G:C	A144P	0.995
8:144501696:G:C	K460N	0.995
8:144501696:G:T	K460N	0.995
8:144498824:T:C	L105P	0.994
8:144498919:T:C	C112R	0.994
8:144499004:C:G	P140R	0.994
8:144500756:C:A	P301H	0.994
8:144497280:G:C	R29P	0.993
8:144498830:C:A	A107D	0.993

dbSNP variants (sampled 300 via entrez): RS1000157569 (8:144501278 G>C), RS1000385364 (8:144492546 A>G), RS1000462056 (8:144501501 G>A,C), RS1000462740 (8:144487259 C>T), RS1000511214 (8:144492251 C>T), RS1000544130 (8:144492143 G>A), RS1000560869 (8:144477889 C>A,G,T), RS1000575226 (8:144486947 T>C), RS1000695965 (8:144481381 G>A,T), RS1000713089 (8:144487178 G>A), RS1000719901 (8:144476381 T>A,C), RS1000807000 (8:144497013 G>A), RS1000829113 (8:144481552 G>A), RS1000882134 (8:144492387 G>T), RS1000978285 (8:144481613 T>C)

Disease associations

OMIM: gene MIM:609172 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002598_30	Educational attainment	9.000000e-06
GCST003795_8	Age at first birth	6.000000e-07
GCST004605_45	Mean corpuscular hemoglobin concentration	9.000000e-17
GCST006045_10	Age at first birth	6.000000e-09
GCST006879_12	Blood metabolite levels	4.000000e-10
GCST006879_13	Blood metabolite levels	2.000000e-09
GCST006879_14	Blood metabolite levels	2.000000e-11
GCST006879_5	Blood metabolite levels	2.000000e-12
GCST008163_246	Height	8.000000e-07
GCST90002391_238	Mean corpuscular hemoglobin concentration	1.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0009101	age at first birth measurement
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Benzo(a)pyrene	decreases expression	3
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
mercuric bromide	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Smoke	decreases expression, increases abundance, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	decreases expression, increases activity, affects binding	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Carcinogens	decreases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3EI	Abcam HEK293T PPP1R16A KO	Transformed cell line	Female
CVCL_TF66	HAP1 PPP1R16A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.