TMEM50B

Summary

TMEM50B (transmembrane protein 50B, HGNC:1280) is a protein-coding gene on chromosome 21q22.11, encoding Transmembrane protein 50B (P56557).

Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway. Located in endoplasmic reticulum.

Source: NCBI Gene 757 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_006134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1280
Approved symbol	TMEM50B
Name	transmembrane protein 50B
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142188
Ensembl biotype	protein_coding
OMIM	617894
Entrez	757

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000420455, ENST00000432504, ENST00000441128, ENST00000442441, ENST00000459909, ENST00000468874, ENST00000470682, ENST00000474272, ENST00000484377, ENST00000542230, ENST00000898431, ENST00000898432, ENST00000927905, ENST00000957757, ENST00000957758, ENST00000957759

RefSeq mRNA: 1 — MANE Select: NM_006134 NM_006134

CCDS: CCDS13625

Canonical transcript exons

ENST00000542230 — 7 exons

Exon	Start	End
ENSE00001490415	33449141	33450863
ENSE00001874127	33479838	33479974
ENSE00002432940	33467010	33467122
ENSE00002433737	33468787	33468926
ENSE00002464649	33465342	33465409
ENSE00003500050	33460413	33460505
ENSE00003620269	33455727	33455784

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8671 / max 288.0773, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190252	22.6297	1812
190250	1.3345	757
190253	1.0317	703
190251	0.8712	501

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	98.44	gold quality
left lobe of thyroid gland	UBERON:0001120	98.19	gold quality
thyroid gland	UBERON:0002046	98.13	gold quality
left ovary	UBERON:0002119	97.40	gold quality
ovary	UBERON:0000992	97.10	gold quality
tibial nerve	UBERON:0001323	96.93	gold quality
right ovary	UBERON:0002118	96.92	gold quality
right lung	UBERON:0002167	96.80	gold quality
left uterine tube	UBERON:0001303	96.77	gold quality
cerebellar hemisphere	UBERON:0002245	96.68	gold quality
cerebellar cortex	UBERON:0002129	96.66	gold quality
cerebellum	UBERON:0002037	96.59	gold quality
mucosa of stomach	UBERON:0001199	96.30	gold quality
fallopian tube	UBERON:0003889	96.20	gold quality
pituitary gland	UBERON:0000007	96.13	gold quality
adenohypophysis	UBERON:0002196	96.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.13	gold quality
prostate gland	UBERON:0002367	96.03	gold quality
body of uterus	UBERON:0009853	96.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.90	gold quality
endocervix	UBERON:0000458	95.87	gold quality
fundus of stomach	UBERON:0001160	95.66	gold quality
body of pancreas	UBERON:0001150	95.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.58	gold quality
lower esophagus	UBERON:0013473	95.57	gold quality
sural nerve	UBERON:0015488	95.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.42	gold quality
hypothalamus	UBERON:0001898	95.36	gold quality
myometrium	UBERON:0001296	95.33	gold quality
right testis	UBERON:0004534	95.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.71
E-MTAB-7606	no	166.61
E-MTAB-7303	no	135.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

150 targeting TMEM50B, 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-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem50b	ENSMUSG00000022964
rattus_norvegicus	Tmem50b	ENSRNOG00000002028
drosophila_melanogaster	CG15012	FBGN0035528
caenorhabditis_elegans	Y74C10AL.2	WBGENE00022280

Paralogs (1): TMEM50A (ENSG00000183726)

Protein

Protein identifiers

Transmembrane protein 50B — P56557 (reviewed: P56557)

Alternative names: HCV p7-trans-regulated protein 3

All UniProt accessions (4): P56557, C9K0I4, F8WBF4, F8WDH1

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. May form homotrimers or homodimers.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane.

Similarity. Belongs to the UPF0220 family.

RefSeq proteins (1): NP_006125* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007919	UPF0220	Family

Pfam: PF05255

UniProt features (7 total): transmembrane region 4, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56557-F1	83.01	0.51

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 204 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, ELVIDGE_HYPOXIA_DN, TGCACTT_MIR519C_MIR519B_MIR519A, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_VACUOLAR_TRANSPORT, MORI_IMMATURE_B_LYMPHOCYTE_UP, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, TERAMOTO_OPN_TARGETS_CLUSTER_1, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_MULTIVESICULAR_BODY_SORTING_PATHWAY, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, TGANTCA_AP1_C

GO Biological Process (1): late endosome to vacuole transport via multivesicular body sorting pathway (GO:0032511)

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

GO Cellular Component (6): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
endosome transport via multivesicular body sorting pathway	1
late endosome to vacuole transport	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM50B	DONSON	Q9NYP3	641
TMEM50B	GART	P22102	599
TMEM50B	MRPS6	P82932	585
TMEM50B	DNAJC28	Q9NX36	577
TMEM50B	PAXBP1	Q9Y5B6	492
TMEM50B	DOP1B	Q9Y3R5	488
TMEM50B	CRYZL1	O95825	485
TMEM50B	SERGEF	Q9UGK8	432
TMEM50B	TBATA	Q96M53	432
TMEM50B	SYNGR2	O43760	431
TMEM50B	IFNGR2	P38484	426
TMEM50B	ZCCHC24	Q8N2G6	393
TMEM50B	PIGV	Q9NUD9	389
TMEM50B	IL10RB	Q08334	382
TMEM50B	GET1	O00258	379

IntAct

69 interactions, top by confidence:

A	B	Type	Score
TMEM50B	LEPROT	psi-mi:“MI:0915”(physical association)	0.560
LEPROT	TMEM50B	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	TMX2	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	EDA	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	GPX8	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	BCL2L1	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	GPR152	psi-mi:“MI:0915”(physical association)	0.560
LEPROTL1	TMEM50B	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	FXYD3	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	HLA-DPA1	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	CLRN1	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	TMEM52B	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	SLC16A13	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	SLC35C2	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
NCR1	TMEM50B	psi-mi:“MI:0915”(physical association)	0.560
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (24): TMEM50B (Affinity Capture-RNA), TMEM50B (Affinity Capture-MS), TMEM50B (Two-hybrid), TMEM50B (Two-hybrid), TMEM50B (Two-hybrid), TMEM50B (Two-hybrid), TMEM50B (Two-hybrid), SLC10A6 (Two-hybrid), CREB3L1 (Two-hybrid), EDA (Two-hybrid), CLRN1 (Two-hybrid), GPX8 (Two-hybrid), TMEM52B (Two-hybrid), SCN3B (Two-hybrid), TMEM88 (Two-hybrid)

ESM2 similar proteins: A2VDC7, A4FUZ5, A9CAZ8, B9TRX0, O15243, O89013, O95807, P04116, P23289, P23294, P36963, P36965, P47789, P47790, P56557, P60201, P60202, P60203, Q0P442, Q0P467, Q13491, Q13530, Q1E1E0, Q3SYT0, Q3SZL9, Q3T110, Q3ZC23, Q4R6L9, Q561T9, Q566G2, Q5PSV5, Q5R4C3, Q5R533, Q5R603, Q5R6E6, Q5ZJD9, Q712P7, Q7TNK0, Q7Z0Q2, Q803X0

Diamond homologs: A9CAZ8, O95807, P56557, Q3SZL9, Q54T60, Q5R4C3, Q9CXL1, Q9D1X9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1630 predictions. Top by Δscore:

Variant	Effect	Δscore
21:33432709:TTTAG:T	acceptor_loss	1.0000
21:33432710:TTAGC:T	acceptor_loss	1.0000
21:33432712:A:AG	acceptor_gain	1.0000
21:33432712:AG:A	acceptor_loss	1.0000
21:33432713:G:GA	acceptor_gain	1.0000
21:33436816:A:AG	acceptor_gain	1.0000
21:33436817:A:G	acceptor_gain	1.0000
21:33436826:A:G	acceptor_gain	1.0000
21:33436827:G:GG	acceptor_gain	1.0000
21:33467004:ACTT:A	donor_loss	1.0000
21:33467005:CT:C	donor_loss	1.0000
21:33467008:A:AC	donor_gain	1.0000
21:33467008:ACAT:A	donor_loss	1.0000
21:33467009:C:CA	donor_gain	1.0000
21:33467009:CA:C	donor_gain	1.0000
21:33467009:CATG:C	donor_gain	1.0000
21:33467009:CATGA:C	donor_gain	1.0000
21:33468781:ACTT:A	donor_loss	1.0000
21:33468783:TTACC:T	donor_loss	1.0000
21:33468784:T:TG	donor_loss	1.0000
21:33468785:ACC:A	donor_loss	1.0000
21:33468786:C:G	donor_loss	1.0000
21:33468924:ATCC:A	acceptor_loss	1.0000
21:33468926:CCT:C	acceptor_loss	1.0000
21:33468928:T:C	acceptor_loss	1.0000
21:33479837:CCCAG:C	donor_gain	1.0000
21:33479844:T:TA	donor_gain	1.0000
21:33432713:GC:G	acceptor_gain	0.9900
21:33432713:GCC:G	acceptor_gain	0.9900
21:33432713:GCCT:G	acceptor_gain	0.9900

AlphaMissense

1049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:33450843:C:T	G151E	1.000
21:33460481:C:T	G102D	1.000
21:33460482:C:G	G102R	1.000
21:33467110:A:G	W38R	1.000
21:33467110:A:T	W38R	1.000
21:33468794:C:T	G31D	1.000
21:33468795:C:G	G31R	1.000
21:33450839:T:A	R152S	0.999
21:33450839:T:G	R152S	0.999
21:33450840:C:G	R152T	0.999
21:33450844:C:G	G151R	0.999
21:33450844:C:T	G151R	0.999
21:33450848:T:A	K149N	0.999
21:33450848:T:G	K149N	0.999
21:33450850:T:C	K149E	0.999
21:33455727:C:A	S144I	0.999
21:33455736:A:T	I141K	0.999
21:33455744:A:C	N138K	0.999
21:33455744:A:T	N138K	0.999
21:33455766:C:T	G131E	0.999
21:33455767:C:G	G131R	0.999
21:33455767:C:T	G131R	0.999
21:33460436:A:G	L117P	0.999
21:33460443:A:G	W115R	0.999
21:33460443:A:T	W115R	0.999
21:33460448:G:A	S113F	0.999
21:33460448:G:T	S113Y	0.999
21:33460451:G:T	A112D	0.999
21:33460457:A:G	L110P	0.999
21:33460463:C:T	G108E	0.999

dbSNP variants (sampled 300 via entrez): RS1000013165 (21:33437034 G>A,C), RS1000025728 (21:33462046 T>C), RS1000088528 (21:33439371 A>G), RS1000280629 (21:33458882 C>A,T), RS1000380602 (21:33459481 C>T), RS1000602882 (21:33466470 C>G), RS1000628278 (21:33460903 C>T), RS1000719897 (21:33478560 G>T), RS1000726628 (21:33467252 C>A), RS1000791675 (21:33472992 A>C), RS1000859354 (21:33443110 T>TG), RS1000960263 (21:33435043 T>C), RS1000962212 (21:33478284 T>C,G), RS1001060498 (21:33454321 T>C), RS1001072712 (21:33447408 G>A)

Disease associations

OMIM: gene MIM:617894 | disease phenotypes: MIM:614889

GenCC curated gene-disease

Mondo (1): immunodeficiency 28 (MONDO:0013953)

Orphanet (2): Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency (Orphanet:319547), Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (Orphanet:319574)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001729_26	Crohn’s disease	2.000000e-16
GCST002598_2	Educational attainment	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Valproic Acid	increases expression	3
bisphenol A	increases methylation, increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Tunicamycin	increases expression	2
Particulate Matter	increases abundance, affects cotreatment, decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
dimethylarsinous acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
NSC 689534	affects binding, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0RH	Ubigene HeLa TMEM50B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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