PPP1R36

Summary

PPP1R36 (protein phosphatase 1 regulatory subunit 36, HGNC:20097) is a protein-coding gene on chromosome 14q23.3, encoding Protein phosphatase 1 regulatory subunit 36 (Q96LQ0). Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.

Predicted to enable phosphatase binding activity and protein phosphatase inhibitor activity.

Source: NCBI Gene 145376 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 77 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_172365

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20097
Approved symbol	PPP1R36
Name	protein phosphatase 1 regulatory subunit 36
Location	14q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165807
Ensembl biotype	protein_coding
OMIM	619923
Entrez	145376

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000298705, ENST00000467261, ENST00000554400, ENST00000555645, ENST00000556023, ENST00000557202, ENST00000884822, ENST00000927760

RefSeq mRNA: 1 — MANE Select: NM_172365 NM_172365

CCDS: CCDS9767

Canonical transcript exons

ENST00000298705 — 12 exons

Exon	Start	End
ENSE00001096798	64589152	64589381
ENSE00001096804	64549961	64550066
ENSE00003511389	64574455	64574589
ENSE00003535674	64588104	64588295
ENSE00003599008	64587194	64587372
ENSE00003602492	64565357	64565454
ENSE00003610891	64565626	64565692
ENSE00003617545	64550921	64550985
ENSE00003627530	64552814	64552861
ENSE00003641136	64564751	64564837
ENSE00003678750	64586837	64586879
ENSE00003788087	64568349	64568447

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 98.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3223 / max 55.4835, expressed in 106 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140121	0.2005	82
140120	0.1218	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.27	gold quality
bronchial epithelial cell	CL:0002328	93.96	gold quality
left testis	UBERON:0004533	92.50	gold quality
bronchus	UBERON:0002185	92.37	gold quality
right testis	UBERON:0004534	92.10	gold quality
testis	UBERON:0000473	90.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.91	gold quality
parotid gland	UBERON:0001831	88.60	gold quality
right uterine tube	UBERON:0001302	87.99	gold quality
epithelial cell of pancreas	CL:0000083	87.57	silver quality
oviduct epithelium	UBERON:0004804	86.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.54	gold quality
adult organism	UBERON:0007023	85.06	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.78	gold quality
body of pancreas	UBERON:0001150	82.25	gold quality
kidney epithelium	UBERON:0004819	80.11	gold quality
nasal cavity mucosa	UBERON:0001826	79.73	gold quality
epithelium of nasopharynx	UBERON:0001951	79.02	silver quality
nasal cavity epithelium	UBERON:0005384	79.00	silver quality
pancreas	UBERON:0001264	78.82	gold quality
fallopian tube	UBERON:0003889	78.77	gold quality
ileal mucosa	UBERON:0000331	78.46	gold quality
rectum	UBERON:0001052	78.30	gold quality
caput epididymis	UBERON:0004358	78.13	gold quality
calcaneal tendon	UBERON:0003701	77.61	gold quality
duodenum	UBERON:0002114	77.04	gold quality
colonic mucosa	UBERON:0000317	77.01	gold quality
islet of Langerhans	UBERON:0000006	75.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	75.69	gold quality
mucosa of transverse colon	UBERON:0004991	75.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.33

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp1r36	ENSMUSG00000052221
rattus_norvegicus	Ppp1r36	ENSRNOG00000038480
drosophila_melanogaster	CG14689	FBGN0037826
drosophila_melanogaster	CG31391	FBGN0051391
drosophila_melanogaster	CG31467	FBGN0051467

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 36 — Q96LQ0 (reviewed: Q96LQ0)

All UniProt accessions (4): E9PLB5, Q96LQ0, G3V4N3, G3V5S6

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.

Subunit / interactions. Interacts with PPP1CA.

RefSeq proteins (1): NP_758953* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026142	Pro_pase_1_reg_su_36	Family

Pfam: PF14895

UniProt features (3 total): sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LQ0-F1	68.85	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): OCT1_06, chr14q23, GOMF_PHOSPHATASE_INHIBITOR_ACTIVITY, GOMF_PHOSPHATASE_BINDING, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_PHOSPHATASE_REGULATOR_ACTIVITY, H1_6_TARGET_GENES, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_STOMACH_CILIATED_EPITHELIAL_CELLS, TRAVAGLINI_LUNG_CILIATED_CELL, TRAVAGLINI_LUNG_PROXIMAL_CILIATED_CELL, GSE19825_NAIVE_VS_IL2RAHIGH_DAY3_EFF_CD8_TCELL_UP

GO Biological Process (1): negative regulation of phosphatase activity (GO:0010923)

GO Molecular Function (2): protein phosphatase inhibitor activity (GO:0004864), phosphatase binding (GO:0019902)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of phosphatase activity	1
phosphatase activity	1
negative regulation of dephosphorylation	1
negative regulation of hydrolase activity	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
enzyme binding	1

Protein interactions and networks

STRING

258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R36	C2orf92	A0A1B0GVN3	720
PPP1R36	C10orf120	Q5SQS8	570
PPP1R36	DNAJC24	Q6P3W2	524
PPP1R36	HSPBAP1	Q96EW2	503
PPP1R36	WDR93	Q6P2C0	452
PPP1R36	SERPINE3	A8MV23	449
PPP1R36	PLEKHG3	A1L390	439
PPP1R36	FAM50B	Q9Y247	435
PPP1R36	IGSF11	Q5DX21	420
PPP1R36	IGSF21	Q96ID5	419
PPP1R36	CCDC125	Q86Z20	401
PPP1R36	GXYLT2	A0PJZ3	379
PPP1R36	ICA1L	Q8NDH6	373
PPP1R36	EPG5	Q9HCE0	371
PPP1R36	DNAJC13	O75165	368

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PPP1R36	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R36	PDS5B	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): PPP1R36 (Synthetic Lethality), PDS5B (Proximity Label-MS), ZNF800 (Cross-Linking-MS (XL-MS)), PPP1R36 (Cross-Linking-MS (XL-MS)), PPP1R36 (Cross-Linking-MS (XL-MS)), PPP1R36 (Cross-Linking-MS (XL-MS)), PPP1R36 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GVB3, A6NHR8, O12165, O93036, P03319, P03320, P04600, P04603, P04862, P05856, P05859, P05861, P05862, P0C657, P10260, P11262, P12482, P14253, P18038, P18801, P19501, P19545, P20867, P20886, P24741, P27979, P29169, P31818, P34706, P36353, P50807, P69738, Q02840, Q09424, Q496A3, Q68FQ8, Q6ZV65, Q75009, Q87043, Q8N9R6

Diamond homologs: D3Z0R2, Q68FW6, Q96LQ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2174 predictions. Top by Δscore:

Variant	Effect	Δscore
14:64550030:G:GT	donor_gain	1.0000
14:64550063:GGAT:G	donor_gain	1.0000
14:64550064:GATG:G	donor_gain	1.0000
14:64550067:G:GG	donor_gain	1.0000
14:64564746:TGCA:T	acceptor_loss	1.0000
14:64564747:GCA:G	acceptor_loss	1.0000
14:64564748:CAGTT:C	acceptor_loss	1.0000
14:64564749:A:AG	acceptor_gain	1.0000
14:64564749:A:G	acceptor_loss	1.0000
14:64564750:G:GC	acceptor_gain	1.0000
14:64564750:GT:G	acceptor_gain	1.0000
14:64564750:GTT:G	acceptor_gain	1.0000
14:64564750:GTTT:G	acceptor_gain	1.0000
14:64564750:GTTTT:G	acceptor_gain	1.0000
14:64565452:AAT:A	donor_gain	1.0000
14:64565452:AATGT:A	donor_loss	1.0000
14:64565453:AT:A	donor_gain	1.0000
14:64565454:TGT:T	donor_loss	1.0000
14:64565455:G:C	donor_loss	1.0000
14:64565455:G:GG	donor_gain	1.0000
14:64565456:TGA:T	donor_loss	1.0000
14:64565457:G:GT	donor_loss	1.0000
14:64565458:AGT:A	donor_loss	1.0000
14:64568335:A:AG	acceptor_gain	1.0000
14:64568336:A:G	acceptor_gain	1.0000
14:64568448:G:GG	donor_gain	1.0000
14:64568452:G:GG	donor_gain	1.0000
14:64574587:A:T	donor_gain	1.0000
14:64574590:G:GG	donor_gain	1.0000
14:64587188:TTGTA:T	acceptor_loss	1.0000

AlphaMissense

2798 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:64587296:T:C	F272L	0.988
14:64587298:C:A	F272L	0.988
14:64587298:C:G	F272L	0.988
14:64550945:T:A	W32R	0.983
14:64550945:T:C	W32R	0.983
14:64565453:A:C	K122N	0.979
14:64565453:A:T	K122N	0.979
14:64587233:T:C	F251L	0.979
14:64587235:C:A	F251L	0.979
14:64587235:C:G	F251L	0.979
14:64565449:T:A	V121D	0.978
14:64586874:T:C	F236L	0.975
14:64586876:T:A	F236L	0.975
14:64586876:T:G	F236L	0.975
14:64587301:C:A	N273K	0.975
14:64587301:C:G	N273K	0.975
14:64587209:T:C	C243R	0.974
14:64587222:C:A	A247D	0.974
14:64587285:G:C	R268P	0.973
14:64568372:T:C	L153P	0.971
14:64587231:T:A	V250D	0.970
14:64574531:T:C	Y204H	0.968
14:64589156:G:C	G363R	0.967
14:64587224:T:A	W248R	0.966
14:64587224:T:C	W248R	0.966
14:64588160:T:A	V316D	0.963
14:64574531:T:G	Y204D	0.962
14:64587368:T:C	F296L	0.962
14:64587370:C:A	F296L	0.962
14:64587370:C:G	F296L	0.962

dbSNP variants (sampled 300 via entrez): RS1000041017 (14:64559729 T>G), RS1000166424 (14:64577140 G>A,C), RS1000222785 (14:64586084 C>T), RS1000294612 (14:64585703 T>C), RS1000497402 (14:64559974 G>A,C), RS1000551661 (14:64552359 G>A), RS1000573485 (14:64581251 G>A), RS1000651839 (14:64559302 T>C), RS1000702525 (14:64559007 G>A), RS1000810608 (14:64554265 C>T), RS1000915462 (14:64573179 A>G), RS1000986930 (14:64572904 C>T), RS1001002380 (14:64552157 G>C), RS1001156132 (14:64550167 T>G), RS1001193109 (14:64559259 A>G)

Disease associations

OMIM: gene MIM:619923 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Limited	Autosomal recessive

Mondo (2): autism (MONDO:0005260), (MONDO:0018393)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009723_89	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-07
GCST009724_58	Vertical cup-disc ratio (multi-trait analysis)	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
aristolochic acid I	increases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
pentanal	decreases expression	1
(+)-JQ1 compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Zinc	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms