TMEM89

Summary

TMEM89 (transmembrane protein 89, HGNC:32372) is a protein-coding gene on chromosome 3p21.31, encoding Transmembrane protein 89 (A2RUT3).

Located in nucleus.

Source: NCBI Gene 440955 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001008269

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32372
Approved symbol	TMEM89
Name	transmembrane protein 89
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183396
Ensembl biotype	protein_coding
Entrez	440955

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000330862

RefSeq mRNA: 1 — MANE Select: NM_001008269 NM_001008269

CCDS: CCDS33751

Canonical transcript exons

ENST00000330862 — 2 exons

Exon	Start	End
ENSE00001290658	48621463	48621769
ENSE00001309587	48620759	48621027

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 96.28.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0252 / max 29.7716, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42157	0.0252	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.28	gold quality
left testis	UBERON:0004533	84.50	gold quality
testis	UBERON:0000473	83.31	gold quality
right testis	UBERON:0004534	83.24	gold quality
mucosa of transverse colon	UBERON:0004991	63.39	gold quality
popliteal artery	UBERON:0002250	63.21	gold quality
tibial artery	UBERON:0007610	63.19	gold quality
transverse colon	UBERON:0001157	61.82	gold quality
descending thoracic aorta	UBERON:0002345	60.45	gold quality
body of stomach	UBERON:0001161	58.43	gold quality
bone marrow	UBERON:0002371	58.40	gold quality
thoracic aorta	UBERON:0001515	57.93	gold quality
ascending aorta	UBERON:0001496	57.69	gold quality
left coronary artery	UBERON:0001626	57.64	gold quality
apex of heart	UBERON:0002098	57.08	gold quality
mucosa of stomach	UBERON:0001199	57.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	55.98	gold quality
right coronary artery	UBERON:0001625	55.52	gold quality
granulocyte	CL:0000094	54.86	gold quality
fundus of stomach	UBERON:0001160	54.74	gold quality
stomach	UBERON:0000945	53.53	gold quality
small intestine	UBERON:0002108	53.28	gold quality
bone marrow cell	CL:0002092	51.92	silver quality
metanephros cortex	UBERON:0010533	51.02	gold quality
intestine	UBERON:0000160	50.71	gold quality
colon	UBERON:0001155	50.70	gold quality
rectum	UBERON:0001052	48.74	gold quality
right ovary	UBERON:0002118	47.57	gold quality
stromal cell of endometrium	CL:0002255	47.01	gold quality
left uterine tube	UBERON:0001303	46.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.80

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem89	ENSMUSG00000025652
rattus_norvegicus	Tmem89	ENSRNOG00000031141

Protein

Protein identifiers

Transmembrane protein 89 — A2RUT3 (reviewed: A2RUT3)

All UniProt accessions (1): A2RUT3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001008270* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028069	TMEM89	Family

Pfam: PF15098

UniProt features (7 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2RUT3-F1	62.62	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): ZWANG_DOWN_BY_2ND_EGF_PULSE, chr3p21, GSE10239_NAIVE_VS_MEMORY_CD8_TCELL_DN, GSE20366_TREG_VS_NAIVE_CD4_TCELL_DEC205_CONVERSION_DN, GSE20366_TREG_VS_NAIVE_CD4_TCELL_DN, GSE11367_CTRL_VS_IL17_TREATED_SMOOTH_MUSCLE_CELL_UP, GSE32423_MEMORY_VS_NAIVE_CD8_TCELL_UP, GSE8835_HEALTHY_VS_CLL_CD4_TCELL_DN, GSE37532_TREG_VS_TCONV_CD4_TCELL_FROM_VISCERAL_ADIPOSE_TISSUE_UP, GSE37532_WT_VS_PPARG_KO_LN_TREG_DN, GSE36078_UNTREATED_VS_AD5_INF_MOUSE_LUNG_DC_UP, GSE35543_IN_VIVO_NTREG_VS_CONVERTED_EX_ITREG_DN, GSE46606_IRF4HIGH_VS_WT_CD40L_IL2_IL5_DAY3_STIMULATED_BCELL_DN, GSE46606_IRF4_KO_VS_WT_UNSTIM_BCELL_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM89	IQCF5	A8MTL0	713
TMEM89	LRRCC1	Q9C099	667
TMEM89	GARIN5A	Q6IPT2	608
TMEM89	SPATA31F1	Q6ZU69	583
TMEM89	EFCC1	Q9HA90	580
TMEM89	DYNLT5	Q8N7M0	507
TMEM89	HROB	Q8N3J3	507
TMEM89	LRRIQ3	A6PVS8	507
TMEM89	C3orf18	Q9UK00	480
TMEM89	FSIP2	Q5CZC0	464
TMEM89	OAZ3	Q9UMX2	463
TMEM89	MAGEC3	Q8TD91	447
TMEM89	PLEKHS1	Q5SXH7	445
TMEM89	GPR174	Q9BXC1	399
TMEM89	CST2	P09228	367

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TMEM89	C4A	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (4): C4A (Affinity Capture-MS), C4A (Affinity Capture-MS), C4A (Affinity Capture-MS), UBR4 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0B4J1N3, A0A1B0GTK4, A0A1B0GTR0, A0JNL8, A2RUT3, A4IFR0, C9JUS6, D3ZKM3, E9PXB6, F2Z3F1, O70899, O71302, O93195, O95411, P03165, P04610, P0C7M3, P12912, P13206, P20976, P20977, P29560, P47939, P47940, P69714, Q02919, Q08648, Q1RN00, Q1WG82, Q5PR19, Q66669, Q67923, Q69027, Q69604, Q6PDA7, Q6UWK7, Q80IU5, Q80IU8, Q8N5N4, Q913A9

Diamond homologs: A2RUT3, Q9DA04

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	30
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

107 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48621458:CTCA:C	donor_loss	0.9900
3:48621459:TCA:T	donor_loss	0.9900
3:48621460:CA:C	donor_loss	0.9900
3:48621461:A:AT	donor_loss	0.9900
3:48621462:CCTCA:C	donor_gain	0.9900
3:48621466:AC:A	donor_gain	0.9800
3:48621467:CC:C	donor_gain	0.9800
3:48621025:ATGC:A	acceptor_loss	0.9700
3:48621027:GC:G	acceptor_loss	0.9700
3:48621028:C:A	acceptor_loss	0.9700
3:48621035:C:CT	acceptor_gain	0.9700
3:48621041:C:CT	acceptor_gain	0.9700
3:48621042:A:T	acceptor_gain	0.9700
3:48621036:A:T	acceptor_gain	0.9600
3:48621461:A:AC	donor_gain	0.9600
3:48621462:C:CC	donor_gain	0.9600
3:48621462:CCT:C	donor_gain	0.9600
3:48621026:TG:T	acceptor_gain	0.9500
3:48621022:CGGA:C	acceptor_gain	0.9400
3:48621053:G:GC	acceptor_gain	0.9400
3:48621025:ATGCT:A	acceptor_gain	0.9300
3:48621026:TGCTG:T	acceptor_gain	0.9300
3:48621024:GATG:G	acceptor_gain	0.9200
3:48621025:ATG:A	acceptor_gain	0.9200
3:48621027:GCTGA:G	acceptor_gain	0.9200
3:48621028:C:CC	acceptor_gain	0.9200
3:48621028:CT:C	acceptor_gain	0.9200
3:48621029:T:A	acceptor_gain	0.9200
3:48621035:C:T	acceptor_gain	0.9200
3:48621024:GATGC:G	acceptor_gain	0.9100

AlphaMissense

998 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48621675:A:G	W28R	0.943
3:48621675:A:T	W28R	0.943
3:48621673:C:A	W28C	0.914
3:48621673:C:G	W28C	0.914
3:48621643:C:A	W38C	0.876
3:48621643:C:G	W38C	0.876
3:48620903:A:G	L140P	0.868
3:48621653:A:G	L35S	0.850
3:48621656:T:A	D34V	0.844
3:48620927:A:G	L132P	0.829
3:48621655:G:C	D34E	0.816
3:48621655:G:T	D34E	0.816
3:48620931:C:G	A131P	0.813
3:48621671:T:C	Y29C	0.809
3:48621645:A:G	W38R	0.795
3:48621645:A:T	W38R	0.795
3:48621656:T:C	D34G	0.793
3:48621672:A:G	Y29H	0.787
3:48620933:T:A	D130V	0.784
3:48621639:A:G	C40R	0.784
3:48621656:T:G	D34A	0.780
3:48620924:A:G	L133P	0.778
3:48621657:C:G	D34H	0.776
3:48620870:A:G	I151T	0.767
3:48621671:T:G	Y29S	0.764
3:48621638:C:G	C40S	0.762
3:48621639:A:T	C40S	0.762
3:48621548:G:T	A70D	0.757
3:48621672:A:C	Y29D	0.755
3:48620915:A:T	I136N	0.754

dbSNP variants (sampled 300 via entrez): RS1000503551 (3:48620734 T>A,G), RS1000671517 (3:48621173 T>C), RS1002300500 (3:48622028 G>C), RS1002728801 (3:48623565 C>A,G), RS1004629272 (3:48621286 A>T), RS1006644576 (3:48623656 A>G), RS1007266560 (3:48622865 C>A,T), RS1007975405 (3:48623568 C>T), RS1008487948 (3:48623346 A>G,T), RS1009389113 (3:48622332 C>T), RS1009439917 (3:48620379 A>G), RS1009764030 (3:48621191 G>A), RS1011031217 (3:48622418 C>T), RS1011458756 (3:48622557 G>A), RS1011778738 (3:48623585 G>A)

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

8 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases methylation, affects cotreatment	1
sodium arsenite	decreases expression	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases methylation	1
Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

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