TMEM225

Summary

TMEM225 (transmembrane protein 225, HGNC:32390) is a protein-coding gene on chromosome 11q24.1, encoding Transmembrane protein 225 (Q6GV28). Probably inhibits protein phosphatase 1 (PP1) in sperm via binding to catalytic subunit PPP1CC.

Predicted to enable protein phosphatase 1 binding activity and protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of phosphatase activity. Predicted to be located in inner acrosomal membrane and outer acrosomal membrane.

Source: NCBI Gene 338661 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001013743

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32390
Approved symbol	TMEM225
Name	transmembrane protein 225
Location	11q24.1
Locus type	gene with protein product
Status	Approved
Aliases	PMP22CD, PPP1R154, SPATA47
Ensembl gene	ENSG00000204300
Ensembl biotype	protein_coding
Entrez	338661

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000375026, ENST00000528595

RefSeq mRNA: 2 — MANE Select: NM_001013743 NM_001013743, NM_001363605

CCDS: CCDS31697

Canonical transcript exons

ENST00000375026 — 4 exons

Exon	Start	End
ENSE00001465526	123882920	123883352
ENSE00001465528	123884075	123884209
ENSE00001465531	123884490	123884636
ENSE00001465534	123885245	123885670

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 93.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0515 / max 53.6791, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122924	0.0515	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.40	silver quality
left testis	UBERON:0004533	80.79	gold quality
testis	UBERON:0000473	78.91	gold quality
right testis	UBERON:0004534	77.87	gold quality
adult organism	UBERON:0007023	73.45	gold quality
buccal mucosa cell	CL:0002336	66.66	silver quality
kidney epithelium	UBERON:0004819	63.36	gold quality
cerebellar vermis	UBERON:0004720	60.90	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.33	gold quality
tibialis anterior	UBERON:0001385	53.12	silver quality
myocardium	UBERON:0002349	50.25	gold quality
ileal mucosa	UBERON:0000331	50.00	silver quality
pancreatic ductal cell	CL:0002079	49.08	silver quality
deltoid	UBERON:0001476	48.76	gold quality
quadriceps femoris	UBERON:0001377	48.07	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
tendon of biceps brachii	UBERON:0008188	46.66	gold quality
vastus lateralis	UBERON:0001379	45.71	gold quality
colonic epithelium	UBERON:0000397	45.07	silver quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
thymus	UBERON:0002370	43.15	gold quality
upper leg skin	UBERON:0004262	43.00	silver quality
secondary oocyte	CL:0000655	42.57	gold quality
germinal epithelium of ovary	UBERON:0001304	42.46	gold quality
epithelium of nasopharynx	UBERON:0001951	42.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting TMEM225, 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-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem225	ENSMUSG00000040541
rattus_norvegicus	Tmem225	ENSRNOG00000054439

Protein

Protein identifiers

Transmembrane protein 225 — Q6GV28 (reviewed: Q6GV28)

All UniProt accessions (2): E9PLT9, Q6GV28

UniProt curated annotations — full annotation on UniProt →

Function. Probably inhibits protein phosphatase 1 (PP1) in sperm via binding to catalytic subunit PPP1CC.

Subunit / interactions. Interacts (via RVxF motif) with PPP1CC.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane.

RefSeq proteins (2): NP_001013765, NP_001350534 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033542	TM225	Family
IPR057351	TM225_dom	Domain

Pfam: PF25452

UniProt features (13 total): topological domain 5, transmembrane region 4, sequence variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6GV28-F1	76.30	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GOCC_SECRETORY_GRANULE, GOCC_ACROSOMAL_MEMBRANE, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_ACROSOMAL_VESICLE, chr11q24, MIR196A_1_3P, MIR587, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_4H_ACT_CD4_TCELL_DN, GSE18148_CBFB_KO_VS_WT_TREG_DN, GSE9988_LPS_VS_LOW_LPS_MONOCYTE_UP, GSE1791_CTRL_VS_NEUROMEDINU_IN_T_CELL_LINE_0.8H_DN, GSE3691_IFN_PRODUCING_KILLER_DC_VS_PLASMACYTOID_DC_SPLEEN_DN, GSE9960_HEALTHY_VS_GRAM_NEG_SEPSIS_PBMC_UP, GSE9960_HEALTHY_VS_GRAM_NEG_AND_POS_SEPSIS_PBMC_UP

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

GO Molecular Function (0):

GO Cellular Component (3): acrosomal membrane (GO:0002080), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

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
acrosomal vesicle	1
secretory granule membrane	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM225	TMEM270	Q6UE05	688
TMEM225	FSCN3	Q9NQT6	673
TMEM225	TMEM225B	P0DP42	654
TMEM225	DHRS12	A0PJE2	646
TMEM225	TMCO5A	Q8N6Q1	644
TMEM225	GTSF1L	Q9H1H1	641
TMEM225	GARIN1B	Q96KD3	626
TMEM225	SPATS1	Q496A3	601
TMEM225	NUDT17	P0C025	596
TMEM225	SPACA4	Q8TDM5	582
TMEM225	SPATA3	Q8NHX4	582
TMEM225	TRIM69	Q86WT6	559
TMEM225	TRAFD1	O14545	543
TMEM225	SLC22A14	Q9Y267	474
TMEM225	UBQLN3	Q9H347	474

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TMEM225	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1): TMEM225 (Affinity Capture-Western)

ESM2 similar proteins: A0A494BZU4, A0A7H0DND7, A0JNG0, A2T345, A4IIV4, C4QM85, E7F594, G5EDX4, O02051, O45306, P0DP42, P0DST5, P0DST6, P21061, P24763, P34362, P34363, P53053, Q09282, Q0II41, Q10907, Q11071, Q11085, Q13571, Q20249, Q297K8, Q2KHT4, Q2KJA5, Q32KQ5, Q5DC12, Q5GH77, Q5PQM0, Q5RD28, Q5REZ0, Q5TAH2, Q61168, Q6AXT9, Q6GV27, Q6GV28, Q7K1V5

Diamond homologs: Q32KQ5, Q6GV27, Q6GV28, Q9D9S2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

306 predictions. Top by Δscore:

Variant	Effect	Δscore
11:123885454:C:CT	donor_gain	0.9700
11:123885477:T:TA	donor_gain	0.9700
11:123885597:T:TA	donor_gain	0.9700
11:123885451:C:CT	donor_gain	0.9500
11:123883350:CTC:C	acceptor_gain	0.8800
11:123885455:C:CT	donor_gain	0.8500
11:123885605:T:TA	donor_gain	0.8500
11:123885393:AC:A	donor_gain	0.8400
11:123885394:CC:C	donor_gain	0.8400
11:123885405:T:TA	donor_gain	0.8300
11:123885592:AC:A	donor_gain	0.8200
11:123885593:CC:C	donor_gain	0.8200
11:123885418:TGC:T	donor_gain	0.8000
11:123885492:G:C	donor_gain	0.7900
11:123883350:CTCCT:C	acceptor_gain	0.7700
11:123885602:A:AC	donor_gain	0.7500
11:123885603:C:CC	donor_gain	0.7500
11:123883349:ACTCC:A	acceptor_gain	0.7400
11:123885519:T:A	donor_gain	0.7100
11:123885604:T:C	donor_gain	0.7100
11:123885452:C:CT	donor_gain	0.7000
11:123883349:ACTC:A	acceptor_loss	0.6800
11:123883352:CCTAG:C	acceptor_loss	0.6800
11:123883353:CTAG:C	acceptor_loss	0.6800
11:123883354:T:A	acceptor_loss	0.6800
11:123883355:A:C	acceptor_loss	0.6400
11:123885207:T:TA	donor_gain	0.6400
11:123885598:C:A	donor_gain	0.6400
11:123883366:A:C	acceptor_loss	0.6300
11:123885242:G:T	donor_gain	0.6100

AlphaMissense

1500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:123885329:A:G	W33R	0.960
11:123885329:A:T	W33R	0.960
11:123884500:A:C	S106R	0.959
11:123884500:A:T	S106R	0.959
11:123884502:T:G	S106R	0.959
11:123885278:A:G	W50R	0.958
11:123885278:A:T	W50R	0.958
11:123885282:A:C	S48R	0.954
11:123885282:A:T	S48R	0.954
11:123885284:T:G	S48R	0.954
11:123885327:C:A	W33C	0.948
11:123885327:C:G	W33C	0.948
11:123885276:C:A	W50C	0.947
11:123885276:C:G	W50C	0.947
11:123885371:A:G	W19R	0.937
11:123885371:A:T	W19R	0.937
11:123884167:A:G	L124P	0.932
11:123884599:G:C	S73R	0.932
11:123884599:G:T	S73R	0.932
11:123884601:T:G	S73R	0.932
11:123885252:C:A	W58C	0.932
11:123885252:C:G	W58C	0.932
11:123885254:A:G	W58R	0.922
11:123885254:A:T	W58R	0.922
11:123884575:G:C	N81K	0.921
11:123884575:G:T	N81K	0.921
11:123884142:G:C	F132L	0.918
11:123884142:G:T	F132L	0.918
11:123884144:A:G	F132L	0.918
11:123885319:A:G	L36S	0.917

dbSNP variants (sampled 300 via entrez): RS1000561039 (11:123883725 C>T), RS1001158022 (11:123887655 A>C,G), RS1001357645 (11:123886481 C>T), RS1001808686 (11:123885275 T>TC), RS1001980701 (11:123886840 A>G), RS1002701947 (11:123885171 T>C), RS1003027939 (11:123884983 C>A,T), RS1003360031 (11:123883675 A>T), RS1004428768 (11:123886879 T>C), RS1004710550 (11:123885779 A>T), RS1004778701 (11:123887442 A>C), RS1005218231 (11:123887147 C>G,T), RS1006879862 (11:123885467 G>A,T), RS1007165645 (11:123883943 G>T), RS1007196046 (11:123882794 G>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001834_8	Oleic acid (18:1n-9) levels	3.000000e-06
GCST004751_11	Serum uric acid levels in response to allopurinol in gout	3.000000e-06
GCST004751_16	Serum uric acid levels in response to allopurinol in gout	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
testosterone undecanoate	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Levonorgestrel	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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