TMEM229B

Summary

TMEM229B (transmembrane protein 229B, HGNC:20130) is a protein-coding gene on chromosome 14q24.1, encoding Transmembrane protein 229B (Q8NBD8).

Predicted to act upstream of or within macrophage activation and response to bacterium. Predicted to be located in membrane.

Source: NCBI Gene 161145 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001348543

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20130
Approved symbol	TMEM229B
Name	transmembrane protein 229B
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33387
Ensembl gene	ENSG00000198133
Ensembl biotype	protein_coding
OMIM	619022
Entrez	161145

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000357461, ENST00000554278, ENST00000554480, ENST00000554675, ENST00000555638, ENST00000555994, ENST00000557006, ENST00000869894, ENST00000869895, ENST00000869896, ENST00000869897, ENST00000869898, ENST00000925695, ENST00000925696, ENST00000925697, ENST00000962034, ENST00000962035, ENST00000962036, ENST00000962037, ENST00000962038, ENST00000962039

RefSeq mRNA: 9 — MANE Select: NM_001348543 NM_001348541, NM_001348542, NM_001348543, NM_001348544, NM_001348546, NM_001348547, NM_001348548, NM_001348549, NM_182526

CCDS: CCDS9783

Canonical transcript exons

ENST00000554480 — 3 exons

Exon	Start	End
ENSE00001518680	67470269	67473941
ENSE00001518693	67487000	67487172
ENSE00002453782	67488508	67488721

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 89.58.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3209 / max 48.0399, expressed in 688 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143742	0.9194	385
143738	0.7101	255
143740	0.4102	208
143741	0.1801	82
143745	0.0665	22
143746	0.0279	10
143737	0.0066	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	89.58	gold quality
cerebellar cortex	UBERON:0002129	89.38	gold quality
cerebellum	UBERON:0002037	89.34	gold quality
cerebellar hemisphere	UBERON:0002245	89.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.30	gold quality
pons	UBERON:0000988	89.20	gold quality
granulocyte	CL:0000094	88.75	gold quality
cerebellar vermis	UBERON:0004720	87.94	gold quality
cortical plate	UBERON:0005343	86.48	gold quality
leukocyte	CL:0000738	86.40	gold quality
monocyte	CL:0000576	86.11	gold quality
nasal cavity epithelium	UBERON:0005384	85.20	silver quality
right adrenal gland	UBERON:0001233	83.93	gold quality
right adrenal gland cortex	UBERON:0035827	83.58	gold quality
left adrenal gland	UBERON:0001234	83.43	gold quality
dorsal root ganglion	UBERON:0000044	83.19	gold quality
left adrenal gland cortex	UBERON:0035825	82.86	gold quality
adrenal cortex	UBERON:0001235	82.67	gold quality
adrenal gland	UBERON:0002369	82.67	gold quality
prefrontal cortex	UBERON:0000451	82.37	gold quality
lateral globus pallidus	UBERON:0002476	82.34	gold quality
left ventricle myocardium	UBERON:0006566	81.80	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.63	gold quality
right frontal lobe	UBERON:0002810	81.61	gold quality
substantia nigra pars compacta	UBERON:0001965	81.35	gold quality
adrenal tissue	UBERON:0018303	81.28	gold quality
frontal cortex	UBERON:0001870	80.80	gold quality
anterior cingulate cortex	UBERON:0009835	80.76	gold quality
neocortex	UBERON:0001950	80.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

119 targeting TMEM229B, 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-574-5P	100.00	66.01	989
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6733-5P	99.74	67.94	2759

Literature-anchored findings (GeneRIF, showing 1)

• Integrative Analysis of the Inflammatory Bowel Disease Serum Metabolome Improves Our Understanding of Genetic Etiology and Points to Novel Putative Therapeutic Targets. (PMID:34780722)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem229b	ENSDARG00000060569
mus_musculus	Tmem229b	ENSMUSG00000046157
rattus_norvegicus	Tmem229b	ENSRNOG00000010646

Paralogs (1): TMEM229A (ENSG00000234224)

Protein

Protein identifiers

Transmembrane protein 229B — Q8NBD8 (reviewed: Q8NBD8)

All UniProt accessions (4): G3V2T8, G3V528, Q8NBD8, G3V5K9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TMEM229 family.

RefSeq proteins (9): NP_001335470, NP_001335471, NP_001335472, NP_001335473, NP_001335475, NP_001335476, NP_001335477, NP_001335478, NP_872332 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010540	CmpB_TMEM229	Family

Pfam: PF06541

UniProt features (10 total): topological domain 5, transmembrane region 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBD8-F1	90.61	0.84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): IRF7_01, chr14q24, FOSTER_TOLERANT_MACROPHAGE_UP, NF1_Q6_01, IRF_Q6, HFH1_01, LYF1_01, PU1_Q6, AACTTT_UNKNOWN, GREENBAUM_E2A_TARGETS_DN, FOXJ2_02, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, HUANG_DASATINIB_RESISTANCE_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP

GO Biological Process (2): response to bacterium (GO:0009617), macrophage activation (GO:0042116)

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to other organism	1
myeloid leukocyte activation	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM229B	TMEM131L	A2VDJ0	666
TMEM229B	TMEM175	Q9BSA9	570
TMEM229B	APBA2	Q99767	501
TMEM229B	ANAPC7	Q9UJX3	475
TMEM229B	TMPRSS9	Q7Z410	462
TMEM229B	GON7	Q9BXV9	447
TMEM229B	SYT1	P21579	444
TMEM229B	KDELR3	O43731	443
TMEM229B	NBEA	Q8NFP9	437
TMEM229B	SIPA1L2	Q9P2F8	433
TMEM229B	PRSS53	Q2L4Q9	424
TMEM229B	PTPN13	Q12923	414
TMEM229B	SEMA6A	Q9H2E6	410
TMEM229B	BCKDK	O14874	410
TMEM229B	TTC23	Q5W5X9	392

IntAct

127 interactions, top by confidence:

A	B	Type	Score
TMEM229B	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	NEMP1	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	PIGP	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
PKMYT1	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	PANX1	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
BIK	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
MMGT1	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	GPX8	psi-mi:“MI:0915”(physical association)	0.560
TSNARE1	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	REEP4	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
MUC1	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
HSD17B13	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	MYG1	psi-mi:“MI:0915”(physical association)	0.560
SYT2	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
EBP	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
ACBD5	TMEM229B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (43): TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid), TMEM229B (Two-hybrid)

ESM2 similar proteins: A2VE61, A5PLL7, A6QLM0, B1AZA5, B8BIM2, D3ZXD8, E9PTA2, O35052, O75907, O94759, P48631, P52848, P98191, Q02353, Q05B45, Q0P5C0, Q0VCJ8, Q2QZ14, Q3UHN9, Q4R4U1, Q4R766, Q5EA70, Q5HZE2, Q5R5F8, Q5R7B1, Q61115, Q6DD32, Q6NYY9, Q6P360, Q6PHN7, Q84VT2, Q8BFQ2, Q8C1E7, Q8GZC3, Q8MK44, Q8NBD8, Q8NBT3, Q8VWZ8, Q90693, Q91YD4

Diamond homologs: B2RXF0, B9EJI9, Q08CG9, Q0V9V2, Q5EA70, Q5F3L7, Q8BFQ2, Q8NBD8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1249 predictions. Top by Δscore:

Variant	Effect	Δscore
14:67473938:CTGG:C	acceptor_gain	0.9900
14:67486998:A:AC	donor_gain	0.9900
14:67486999:C:CC	donor_gain	0.9900
14:67533396:G:GT	donor_gain	0.9900
14:67533396:GAGGT:G	donor_loss	0.9900
14:67533397:AGGTG:A	donor_loss	0.9900
14:67533398:GGTG:G	donor_loss	0.9900
14:67533399:GTGA:G	donor_loss	0.9900
14:67533400:T:G	donor_loss	0.9900
14:67473942:C:CC	acceptor_gain	0.9800
14:67486994:A:AC	donor_gain	0.9800
14:67486995:C:CC	donor_gain	0.9800
14:67486995:CTCA:C	donor_gain	0.9800
14:67486999:CTT:C	donor_gain	0.9800
14:67487171:CCCT:C	acceptor_loss	0.9800
14:67487172:CCTG:C	acceptor_loss	0.9800
14:67487173:CTGGG:C	acceptor_loss	0.9800
14:67487174:T:A	acceptor_loss	0.9800
14:67515079:CACCT:C	donor_loss	0.9800
14:67515080:ACCT:A	donor_loss	0.9800
14:67515081:CCTAC:C	donor_loss	0.9800
14:67515082:CT:C	donor_loss	0.9800
14:67515083:TAC:T	donor_loss	0.9800
14:67515084:A:AC	donor_gain	0.9800
14:67515084:ACCGG:A	donor_loss	0.9800
14:67515085:C:CC	donor_gain	0.9800
14:67533395:GGAG:G	donor_gain	0.9800
14:67533399:G:GG	donor_gain	0.9800
14:67533526:G:GT	donor_gain	0.9800
14:67533629:G:GT	donor_gain	0.9800

AlphaMissense

494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:67473742:T:A	E61V	0.999
14:67473763:C:A	G54V	0.999
14:67473763:C:T	G54D	0.999
14:67473764:C:G	G54R	0.999
14:67473782:A:G	W48R	0.999
14:67473782:A:T	W48R	0.999
14:67473786:G:C	S46R	0.999
14:67473786:G:T	S46R	0.999
14:67473788:T:G	S46R	0.999
14:67473796:C:T	G43E	0.999
14:67473797:C:A	G43W	0.999
14:67473797:C:G	G43R	0.999
14:67473797:C:T	G43R	0.999
14:67473838:G:T	A29E	0.999
14:67473843:G:C	F27L	0.999
14:67473843:G:T	F27L	0.999
14:67473845:A:G	F27L	0.999
14:67473852:C:A	E24D	0.999
14:67473852:C:G	E24D	0.999
14:67473853:T:A	E24V	0.999
14:67473865:C:T	G20D	0.999
14:67473866:C:G	G20R	0.999
14:67473787:C:A	S46I	0.998
14:67473790:G:C	T45R	0.998
14:67473790:G:T	T45K	0.998
14:67473839:C:G	A29P	0.998
14:67473844:A:G	F27S	0.998
14:67473874:G:T	A17D	0.998
14:67473875:C:G	A17P	0.998
14:67473698:G:T	R76S	0.997

dbSNP variants (sampled 300 via entrez): RS1000053876 (14:67534513 ATTG>A), RS1000060501 (14:67494761 C>G,T), RS1000190515 (14:67489746 A>T), RS1000223497 (14:67510438 G>C), RS1000363665 (14:67524065 C>G), RS1000393704 (14:67475674 G>A), RS1000475638 (14:67490697 G>A,C), RS1000478297 (14:67477347 A>C,G,T), RS1000528578 (14:67531350 A>T), RS1000539508 (14:67495046 C>T), RS1000573438 (14:67502479 G>A), RS1000598407 (14:67529638 A>G), RS1000711764 (14:67524917 A>C), RS1000712931 (14:67485644 C>T), RS1000731560 (14:67515103 C>CG)

Disease associations

OMIM: gene MIM:619022 | disease phenotypes: MIM:612712

GenCC curated gene-disease

Mondo (1): Leber congenital amaurosis 13 (MONDO:0012990)

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001762_712	Obesity-related traits	5.000000e-08
GCST002544_2	Parkinson’s disease	7.000000e-14
GCST003139_1	Glomerular filtration rate in chronic kidney disease	9.000000e-06
GCST004902_8	Parkinson’s disease	1.000000e-10
GCST005648_27	Serum metabolite concentrations in chronic kidney disease	2.000000e-12
GCST005648_28	Serum metabolite concentrations in chronic kidney disease	2.000000e-08
GCST005650_213	Serum metabolite ratios in chronic kidney disease	3.000000e-16
GCST005650_214	Serum metabolite ratios in chronic kidney disease	4.000000e-21
GCST005650_215	Serum metabolite ratios in chronic kidney disease	3.000000e-14
GCST005650_216	Serum metabolite ratios in chronic kidney disease	6.000000e-16
GCST005650_217	Serum metabolite ratios in chronic kidney disease	2.000000e-20
GCST005650_218	Serum metabolite ratios in chronic kidney disease	5.000000e-30
GCST005650_219	Serum metabolite ratios in chronic kidney disease	5.000000e-22
GCST006631_16	Nicotine dependence and major depression (severity of comorbidity)	6.000000e-06
GCST010002_155	Refractive error	6.000000e-11
GCST012020_346	Serum metabolite levels	3.000000e-30
GCST012020_347	Serum metabolite levels	2.000000e-14
GCST012020_348	Serum metabolite levels	6.000000e-66
GCST012020_349	Serum metabolite levels	4.000000e-85
GCST012299_15	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	1.000000e-05
GCST90002380_25	Basophil percentage of white cells	1.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:0008343	sex interaction measurement
EFO:0007992	basophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567197	Leber Congenital Amaurosis 13 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, decreases reaction, increases expression	3
(+)-JQ1 compound	decreases expression	2
Nickel	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
GSK-J4	decreases expression	1
mivebresib	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Doxorubicin	increases expression	1
Lead	affects expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Magnetite Nanoparticles	increases methylation	1

Clinical trials (associated diseases)

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