PPP1R42

Summary

PPP1R42 (protein phosphatase 1 regulatory subunit 42, HGNC:33732) is a protein-coding gene on chromosome 8q13.1, encoding Protein phosphatase 1 regulatory subunit 42 (Q7Z4L9). Regulates phosphatase activity of protein phosphatase 1 (PP1) complexes in the testis.

The protein encoded by this gene can interact with gamma-tubulin and PP1 phosphatase, a regulator of centrosome separation. The encoded protein is a positive regulator of PP1 phosphatase and thus plays a role in the control of centrosome integrity.

Source: NCBI Gene 286187 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_001364910

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33732
Approved symbol	PPP1R42
Name	protein phosphatase 1 regulatory subunit 42
Location	8q13.1
Locus type	gene with protein product
Status	Approved
Aliases	dtr, TLLR
Ensembl gene	ENSG00000178125
Ensembl biotype	protein_coding
OMIM	617720
Entrez	286187

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000324682, ENST00000517834, ENST00000518588, ENST00000519919, ENST00000519987, ENST00000520633, ENST00000521040, ENST00000521410, ENST00000521581, ENST00000521998, ENST00000522331, ENST00000522909, ENST00000523545, ENST00000685739

RefSeq mRNA: 5 — MANE Select: NM_001364910 NM_001013626, NM_001348563, NM_001364910, NM_001364911, NM_001364912

CCDS: CCDS34902, CCDS94299

Canonical transcript exons

ENST00000685739 — 8 exons

Exon	Start	End
ENSE00001286192	67014426	67014592
ENSE00001642031	66982049	66982180
ENSE00003491038	67010715	67010831
ENSE00003532329	66988400	66988517
ENSE00003587413	67012958	67013096
ENSE00003617272	67017619	67017831
ENSE00003929532	66964103	66964334
ENSE00003934055	67028491	67028554

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 97.11.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6336 / max 45.1335, expressed in 207 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93430	0.6336	207

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.09	gold quality
left testis	UBERON:0004533	90.17	gold quality
right testis	UBERON:0004534	90.09	gold quality
testis	UBERON:0000473	89.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.01	gold quality
fallopian tube	UBERON:0003889	78.87	gold quality
thymus	UBERON:0002370	76.54	silver quality
hypothalamus	UBERON:0001898	76.22	gold quality
caudate nucleus	UBERON:0001873	74.56	gold quality
amygdala	UBERON:0001876	73.17	gold quality
pituitary gland	UBERON:0000007	73.06	gold quality
temporal lobe	UBERON:0001871	73.02	gold quality
adenohypophysis	UBERON:0002196	72.95	gold quality
Ammon’s horn	UBERON:0001954	72.67	gold quality
spinal cord	UBERON:0002240	71.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.92	gold quality
substantia nigra	UBERON:0002038	70.70	gold quality
nucleus accumbens	UBERON:0001882	70.59	gold quality
quadriceps femoris	UBERON:0001377	69.42	gold quality
right lung	UBERON:0002167	69.28	gold quality
endometrium	UBERON:0001295	68.09	gold quality
cerebellar vermis	UBERON:0004720	67.75	gold quality
putamen	UBERON:0001874	66.95	gold quality
corpus callosum	UBERON:0002336	66.95	gold quality
endocervix	UBERON:0000458	66.53	gold quality
brain	UBERON:0000955	66.13	gold quality
anterior cingulate cortex	UBERON:0009835	65.98	gold quality
cerebral cortex	UBERON:0000956	65.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.70	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.29
E-GEOD-124858	no	6.80
E-GEOD-99795	no	3.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting PPP1R42, 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-548P	99.98	72.25	3784
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-6831-3P	97.49	69.29	505
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-764	94.16	64.85	656

Literature-anchored findings (GeneRIF, showing 1)

• PPP1R42 regulation of PP1 function in centrosome separation. (PMID:23718219)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r42	ENSDARG00000057632
mus_musculus	Ppp1r42	ENSMUSG00000025916
rattus_norvegicus	Ppp1r42	ENSRNOG00000006804
drosophila_melanogaster	TbCMF46	FBGN0032163
drosophila_melanogaster	Ppr-Y	FBGN0046697

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), DNAAF11 (ENSG00000129295), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), DNAAF1 (ENSG00000154099), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), DRC3 (ENSG00000171962), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 42 — Q7Z4L9 (reviewed: Q7Z4L9)

Alternative names: Leucine-rich repeat-containing protein 67

All UniProt accessions (2): A0A8I5KP60, Q7Z4L9

UniProt curated annotations — full annotation on UniProt →

Function. Regulates phosphatase activity of protein phosphatase 1 (PP1) complexes in the testis.

Subunit / interactions. Interacts with PPP1CC isoform gamma-2; the interaction is direct. Interacts with actin, dynein, KIF5B, KIFC1 and tubulin. Associates with microtubules.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. Phosphorylated; in the testis.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z4L9-1	1	yes
Q7Z4L9-2	2

RefSeq proteins (4): NP_001013648, NP_001351839, NP_001351840, NP_001351841 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR025875	Leu-rich_rpt_4	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050836	SDS22/Internalin_LRR	Family

Pfam: PF12799, PF14580

UniProt features (11 total): repeat 7, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4L9-F1	86.02	0.75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (0):

GO Molecular Function (4): actin binding (GO:0003779), tubulin binding (GO:0015631), dynein complex binding (GO:0070840), protein binding (GO:0005515)

GO Cellular Component (6): manchette (GO:0002177), centrosome (GO:0005813), microtubule organizing center (GO:0005815), microtubule cytoskeleton (GO:0015630), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoskeletal protein binding	2
microtubule cytoskeleton	2
protein-containing complex binding	1
binding	1
centriole	1
microtubule organizing center	1
cytoskeleton	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1993 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R42	KIF5B	P33176	513
PPP1R42	DYNC1I1	O14576	512
PPP1R42	LRRC39	Q96DD0	481
PPP1R42	ACTG1	P02571	475
PPP1R42	MYO5A	Q9Y4I1	436
PPP1R42	CFAP73	A6NFT4	410
PPP1R42	MYH10	P35580	407
PPP1R42	TDRD15	B5MCY1	406
PPP1R42	FAM228B	P0C875	404
PPP1R42	KCTD18	Q6PI47	400
PPP1R42	ERICH2	A1L162	399
PPP1R42	PPP1R2	P41236	399
PPP1R42	MYH9	P35579	398
PPP1R42	PRSS37	A4D1T9	398
PPP1R42	RRH	O14718	398

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PPP1R42	NCL	psi-mi:“MI:0915”(physical association)	0.400
PPP1R42	htpG	psi-mi:“MI:0915”(physical association)	0.370
PPP1R42		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): PPP1R42 (Proximity Label-MS), PPP1R42 (Affinity Capture-MS), PPP1R42 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A6QLV3, A7SFP1, A8XWW4, B0W6M9, B3LWU3, B3P3E8, B4IBI9, B4JTV9, B4LXW1, B4N9T4, B4PU77, B4QVR7, B5DX45, B6CZ61, B9F655, O35125, O88520, Q1L8Y7, Q22875, Q32KP2, Q4R3P6, Q4V8I7, Q53EV4, Q5F4C4, Q5FVI3, Q5GIG6, Q5M8G4, Q5RAV5, Q5RFE9, Q5ZLN0, Q6AYI5, Q6DHL5, Q6GPJ5, Q6INV3, Q6P1C6, Q6UXM1, Q6ZVD8, Q7SXW3, Q7Z4L9, Q80VQ1

Diamond homologs: B3NLX1, B4P6W7, Q4R803, Q5PPX0, Q6GQN5, Q7Z4L9, Q8INT5, Q8R1Z4, Q755D2, O35381, O43423, O95626, P09661, P39687, P43333, P49911, P51122, P57784, Q28XE2, Q3SZC6, Q4P5F9, Q4R8Y8, Q4WV66, Q5A449, Q5BGW9, Q5ZMN0, Q64G17, Q6A1I3, Q6BT60, Q6C417, Q6P1U7, Q6PAF6, Q7S9P4, Q7ZUP0, Q8AVC1, Q8GRL7, Q8HY67, Q92688, Q9BLB6, Q9D3R3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1715 predictions. Top by Δscore:

Variant	Effect	Δscore
8:67010709:CACTA:C	donor_gain	1.0000
8:67010710:ACTAC:A	donor_loss	1.0000
8:67010711:CTACC:C	donor_loss	1.0000
8:67010714:CC:C	donor_loss	1.0000
8:67010714:CCT:C	donor_gain	1.0000
8:67010827:GATTT:G	acceptor_gain	1.0000
8:67010828:ATTT:A	acceptor_gain	1.0000
8:67010829:TTT:T	acceptor_gain	1.0000
8:67010830:TT:T	acceptor_gain	1.0000
8:67010830:TTC:T	acceptor_loss	1.0000
8:67010831:TC:T	acceptor_loss	1.0000
8:67010832:C:CC	acceptor_gain	1.0000
8:67010833:T:A	acceptor_loss	1.0000
8:67012956:A:AC	donor_gain	1.0000
8:67012957:C:CC	donor_gain	1.0000
8:67012957:CTG:C	donor_gain	1.0000
8:67017617:A:AC	donor_gain	1.0000
8:67017618:C:CC	donor_gain	1.0000
8:67028416:A:AC	donor_gain	1.0000
8:67028417:C:CC	donor_gain	1.0000
8:67045806:TCTTA:T	donor_loss	1.0000
8:67045807:CTTAC:C	donor_loss	1.0000
8:67045808:TTAC:T	donor_loss	1.0000
8:67045809:TAC:T	donor_loss	1.0000
8:67045810:A:T	donor_loss	1.0000
8:67045811:C:CG	donor_loss	1.0000
8:67045811:CCTGT:C	donor_gain	1.0000
8:67051225:CTTA:C	donor_loss	1.0000
8:67051226:TTA:T	donor_loss	1.0000
8:67051227:TA:T	donor_loss	1.0000

AlphaMissense

1790 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:67013031:A:G	L121P	0.996
8:67014426:A:G	L99P	0.995
8:66982137:G:C	F238L	0.994
8:66982137:G:T	F238L	0.994
8:66982139:A:G	F238L	0.994
8:67014486:A:G	L79P	0.994
8:67013081:A:C	N104K	0.993
8:67013081:A:T	N104K	0.993
8:67014476:A:C	N82K	0.990
8:67014476:A:T	N82K	0.990
8:66988458:A:C	N204K	0.989
8:66988458:A:T	N204K	0.989
8:67010743:G:T	A175D	0.989
8:66988468:A:G	L201P	0.988
8:67010749:A:G	L173P	0.988
8:66982135:A:G	L239P	0.987
8:67010799:A:C	N156K	0.987
8:67010799:A:T	N156K	0.987
8:67014542:A:C	N60K	0.987
8:67014542:A:T	N60K	0.987
8:67010733:G:C	N178K	0.986
8:67010733:G:T	N178K	0.986
8:67010815:A:G	L151S	0.985
8:67013031:A:T	L121H	0.985
8:67013091:A:G	L101P	0.985
8:67014426:A:T	L99Q	0.983
8:66982174:A:G	L226P	0.982
8:67013031:A:C	L121R	0.981
8:67014426:A:C	L99R	0.980
8:66982138:A:G	F238S	0.979

dbSNP variants (sampled 300 via entrez): RS1000019097 (8:66971790 T>C), RS1000024478 (8:67022947 T>C), RS1000049231 (8:67010573 A>G), RS1000066143 (8:67002390 G>A), RS1000092293 (8:66972180 A>C,G,T), RS1000156092 (8:67001821 T>C), RS1000160291 (8:67002720 G>A), RS1000269263 (8:66992901 C>T), RS1000321949 (8:67010275 T>C), RS1000329242 (8:66985665 C>T), RS1000397715 (8:66985847 G>C,T), RS1000479542 (8:67023264 G>A,C), RS1000501950 (8:67004457 T>C), RS1000575796 (8:66993486 C>T), RS1000658772 (8:66983687 C>T)

Disease associations

OMIM: gene MIM:617720 | disease phenotypes: MIM:615636

GenCC curated gene-disease

Mondo (1): Joubert syndrome 21 (MONDO:0014288)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
Smoke	increases abundance, increases expression	2
arsenite	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
bisphenol S	decreases methylation	1
Atrazine	increases expression	1
Cisplatin	increases response to substance	1
Coal	increases abundance, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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