PPP1R35

Summary

PPP1R35 (protein phosphatase 1 regulatory subunit 35, HGNC:28320) is a protein-coding gene on chromosome 7q22.1, encoding Protein phosphatase 1 regulatory subunit 35 (Q8TAP8). During centriole duplication, plays a role in the centriole elongation by promoting the recruitment of the microtubule-binding elongation machinery through its interaction with RTTN, leading to the centriole to centrosome conversion.

Predicted to enable phosphatase binding activity and protein phosphatase inhibitor activity. Involved in positive regulation of centriole elongation. Located in centriole and centrosome.

Source: NCBI Gene 221908 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 28 total — 1 pathogenic
• MANE Select transcript: NM_145030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28320
Approved symbol	PPP1R35
Name	protein phosphatase 1 regulatory subunit 35
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC22793
Ensembl gene	ENSG00000160813
Ensembl biotype	protein_coding
OMIM	618937
Entrez	221908

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 retained_intron, 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000292330, ENST00000470295, ENST00000476185, ENST00000487452, ENST00000491407, ENST00000966125

RefSeq mRNA: 2 — MANE Select: NM_145030 NM_001346938, NM_145030

CCDS: CCDS5694

Canonical transcript exons

ENST00000292330 — 4 exons

Exon	Start	End
ENSE00001054672	100435848	100436064
ENSE00001921354	100436141	100436497
ENSE00003460545	100435631	100435767
ENSE00003688939	100435282	100435533

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4284 / max 124.0429, expressed in 1789 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85196	12.9586	1787
85195	0.4635	258
85197	0.0063	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.34	gold quality
right testis	UBERON:0004534	95.73	gold quality
left testis	UBERON:0004533	95.68	gold quality
secondary oocyte	CL:0000655	95.26	gold quality
thymus	UBERON:0002370	94.52	gold quality
spleen	UBERON:0002106	94.49	gold quality
granulocyte	CL:0000094	94.41	gold quality
testis	UBERON:0000473	93.79	gold quality
mucosa of transverse colon	UBERON:0004991	93.34	gold quality
lower esophagus mucosa	UBERON:0035834	92.63	gold quality
left adrenal gland cortex	UBERON:0035825	91.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.86	gold quality
adrenal cortex	UBERON:0001235	91.68	gold quality
adenohypophysis	UBERON:0002196	91.66	gold quality
cerebellar vermis	UBERON:0004720	91.49	gold quality
left adrenal gland	UBERON:0001234	91.44	gold quality
cerebellar hemisphere	UBERON:0002245	91.41	gold quality
right adrenal gland	UBERON:0001233	91.37	gold quality
cerebellar cortex	UBERON:0002129	91.37	gold quality
right adrenal gland cortex	UBERON:0035827	91.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.24	gold quality
cerebellum	UBERON:0002037	91.04	gold quality
ileal mucosa	UBERON:0000331	90.88	gold quality
pituitary gland	UBERON:0000007	90.86	gold quality
right lobe of thyroid gland	UBERON:0001119	90.78	gold quality
left uterine tube	UBERON:0001303	90.70	gold quality
left ovary	UBERON:0002119	90.54	gold quality
right ovary	UBERON:0002118	90.39	gold quality
right uterine tube	UBERON:0001302	90.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.22

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Data show that PPP1R35 acts downstream of, and forms a complex with, RTTN, a microcephaly protein required for distal centriole elongation. (PMID:30168418)
• Authors found that PPP1R35 is enriched at newborn daughter centrioles in S or G2 phase. In the absence of PPP1R35, centriole assembly initiates normally in S phase, but none of the nascent centrioles can form active centrosomes or recruit CEP295, an essential factor for CCC. (PMID:30230954)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp1r35	ENSMUSG00000029725
rattus_norvegicus		ENSRNOG00000084887

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 35 — Q8TAP8 (reviewed: Q8TAP8)

All UniProt accessions (1): Q8TAP8

UniProt curated annotations — full annotation on UniProt →

Function. During centriole duplication, plays a role in the centriole elongation by promoting the recruitment of the microtubule-binding elongation machinery through its interaction with RTTN, leading to the centriole to centrosome conversion. In addition, may play a role in the primary cilia assembly.

Subunit / interactions. Interacts with PPP1CA; this interaction mediates the PPP1CA phosphatase activity inhibition. Interacts with RTTN; this interaction allows the mutual recruitment to the centriole.

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

Similarity. Belongs to the PPP1R35 family.

RefSeq proteins (2): NP_001333867, NP_659467* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029135	PPP1R35_C	Domain
IPR033590	PPP1R35	Family

Pfam: PF15503

UniProt features (13 total): mutagenesis site 8, modified residue 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAP8-F1	69.48	0.15

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 (2): 47, 52

Mutagenesis-validated functional residues (8):

Position	Phenotype
52	does not affect centrosome localization; when associated with d-45 and d-47. does not affect interaction with rttn; when
79	does not affect centriole localization; when associated with a-81. does not affect interaction with rttn; when associate
81	does not affect centriole localization; when associated with a-79. does not affect interaction with rttn; when associate
45	does not affect centrosome localization; when associated with a-47 and a-52. does not affect interaction with rttn; when
45	does not affect centrosome localization; when associated with d-47 and d-52. does not affect interaction with rttn; when
47	does not affect centrosome localization; when associated with a-45 and a-52. does not affect interaction with rttn; when
47	does not affect centrosome localization; when associated with d-45 and d-52. does not affect interaction with rttn; when
52	does not affect centrosome localization; when associated with a-45 and a-47. does not affect interaction with rttn; when

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_CENTRIOLE_REPLICATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CENTRIOLE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (4): positive regulation of cilium assembly (GO:0045724), notochord morphogenesis (GO:0048570), positive regulation of centriole elongation (GO:1903724), negative regulation of phosphatase activity (GO:0010923)

GO Molecular Function (3): protein phosphatase inhibitor activity (GO:0004864), phosphatase binding (GO:0019902), protein binding (GO:0005515)

GO Cellular Component (4): centrosome (GO:0005813), centriole (GO:0005814), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule organizing center	2
intracellular membraneless organelle	2
cilium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
notochord development	1
embryonic organ morphogenesis	1
positive regulation of centriole replication	1
centriole elongation	1
regulation of centriole elongation	1
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
binding	1
centriole	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R35	RTTN	Q86VV8	736
PPP1R35	CEP295	Q9C0D2	646
PPP1R35	STIL	Q15468	613
PPP1R35	SPACDR	Q8IZ16	571
PPP1R35	CEP135	Q66GS9	532
PPP1R35	PDXDC1	Q6P996	501
PPP1R35	CCDC9	Q9Y3X0	494
PPP1R35	BAHD1	Q8TBE0	493
PPP1R35	CEP97	Q8IW35	488
PPP1R35	POC5	Q8NA72	478
PPP1R35	NYAP1	Q6ZVC0	454
PPP1R35	KIF20B	Q96Q89	450
PPP1R35	ASDURF	L0R819	447
PPP1R35	TATDN2	Q93075	445
PPP1R35	CEP120	Q8N960	433

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ZMYND11	PPP1R35	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1CA	PPP1R35	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1R35	PPP1CC	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	PPP1R35	psi-mi:“MI:0915”(physical association)	0.370
PPP1R35	PRPF40A	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (12): PPP1R35 (Affinity Capture-MS), EDC4 (Affinity Capture-MS), PRPF40A (Affinity Capture-MS), DCP1A (Affinity Capture-MS), EDC3 (Affinity Capture-MS), DCP2 (Affinity Capture-MS), PPP1R35 (Proximity Label-MS), PPP1R35 (Affinity Capture-RNA), PPP1R35 (Affinity Capture-MS), PPP1R35 (Affinity Capture-MS), PPP1R35 (Two-hybrid), PPP1R35 (Affinity Capture-Western)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2Z4LIS9, A2VE02, A4D1S0, A5PKC7, A5PL33, A6H7B4, A6NEL2, A6QP24, A6QPM6, A8MTW9, A8MYA2, D3ZAQ5, D4AAA5, E7EW31, O75474, O75638, O89113, O94850, P0C7X2, P14652, P50617, P70339, Q2KIS6, Q3UN58, Q5JPB2, Q5VZ46, Q6GQX2, Q6NZ36, Q6ZSJ8, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86UU5, Q8IWN7, Q8N6K4, Q8N944

Diamond homologs: A6QPM6, Q0P427, Q8TAP8, Q9D8C8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1704247	NM_145030.4(PPP1R35):c.753_*3delinsCG (p.Trp251fs)	Pathogenic

SpliceAI

312 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100435678:C:CA	donor_gain	1.0000
7:100435846:AC:A	donor_gain	1.0000
7:100435847:CC:C	donor_gain	1.0000
7:100435862:T:TA	donor_gain	1.0000
7:100435865:T:TA	donor_gain	1.0000
7:100435894:T:A	donor_gain	1.0000
7:100435899:G:C	donor_gain	1.0000
7:100435530:GCTCC:G	acceptor_loss	0.9900
7:100435532:TCC:T	acceptor_loss	0.9900
7:100435533:CCT:C	acceptor_loss	0.9900
7:100435534:C:CG	acceptor_loss	0.9900
7:100435535:T:A	acceptor_loss	0.9900
7:100435625:CATCA:C	donor_loss	0.9900
7:100435626:ATCAC:A	donor_loss	0.9900
7:100435627:TCAC:T	donor_loss	0.9900
7:100435628:CA:C	donor_loss	0.9900
7:100435629:AC:A	donor_loss	0.9900
7:100435630:C:CT	donor_loss	0.9900
7:100435650:G:A	donor_gain	0.9900
7:100435763:CAGCC:C	acceptor_gain	0.9900
7:100435764:AGCCC:A	acceptor_loss	0.9900
7:100435766:CC:C	acceptor_gain	0.9900
7:100435766:CCCTG:C	acceptor_loss	0.9900
7:100435767:CC:C	acceptor_gain	0.9900
7:100435767:CCT:C	acceptor_loss	0.9900
7:100435768:C:CA	acceptor_loss	0.9900
7:100435768:C:CC	acceptor_gain	0.9900
7:100435769:T:A	acceptor_loss	0.9900
7:100435775:C:CT	acceptor_gain	0.9900
7:100435842:CCTCA:C	donor_loss	0.9900

AlphaMissense

1591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100435371:A:G	W251R	0.993
7:100435371:A:T	W251R	0.993
7:100435721:G:C	S166R	0.993
7:100435721:G:T	S166R	0.993
7:100435723:T:G	S166R	0.993
7:100435736:G:C	F161L	0.993
7:100435736:G:T	F161L	0.993
7:100435738:A:G	F161L	0.993
7:100435396:G:C	F242L	0.992
7:100435396:G:T	F242L	0.992
7:100435398:A:G	F242L	0.992
7:100435369:C:A	W251C	0.991
7:100435369:C:G	W251C	0.991
7:100435737:A:G	F161S	0.985
7:100435927:A:C	F124L	0.985
7:100435927:A:T	F124L	0.985
7:100435929:A:G	F124L	0.985
7:100436056:G:C	F81L	0.984
7:100436056:G:T	F81L	0.984
7:100436058:A:G	F81L	0.984
7:100435885:G:C	F138L	0.983
7:100435885:G:T	F138L	0.983
7:100435887:A:G	F138L	0.983
7:100435738:A:T	F161I	0.982
7:100435397:A:G	F242S	0.981
7:100435975:G:C	S108R	0.980
7:100435975:G:T	S108R	0.980
7:100435977:T:G	S108R	0.980
7:100435390:C:A	M244I	0.979
7:100435390:C:G	M244I	0.979

dbSNP variants (sampled 300 via entrez): RS1001031038 (7:100437751 C>G,T), RS1001553730 (7:100435292 A>G), RS1001940656 (7:100435441 G>A), RS1002502362 (7:100435000 C>T), RS1003504474 (7:100436056 G>A), RS1003604140 (7:100438220 T>C), RS1003699135 (7:100437801 C>T), RS1005151491 (7:100437152 A>C), RS1006136654 (7:100438249 A>C,T), RS1006148936 (7:100438600 G>A,T), RS1006724652 (7:100436766 G>A), RS1007125935 (7:100437169 C>T), RS1008585685 (7:100436501 C>G,T), RS1008739164 (7:100434965 A>C,G), RS1009078762 (7:100436657 G>C)

Disease associations

OMIM: gene MIM:618937 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
K 7174	increases expression	1
(+)-JQ1 compound	decreases expression	1
Carbamazepine	affects expression	1
Doxorubicin	increases expression	1
Hydrogen Peroxide	affects expression	1
Ozone	increases abundance, affects expression	1
Smoke	increases abundance, increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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