TMEM39B

Summary

TMEM39B (transmembrane protein 39B, HGNC:25510) is a protein-coding gene on chromosome 1p35.2, encoding Transmembrane protein 39B (Q9GZU3). May protect the cells against DNA damage caused by exposure to the cold-warming stress and facilitates tissue damage repair during the recovery phase.

Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in membrane.

Source: NCBI Gene 55116 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_018056

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25510
Approved symbol	TMEM39B
Name	transmembrane protein 39B
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10315
Ensembl gene	ENSG00000121775
Ensembl biotype	protein_coding
Entrez	55116

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000336294, ENST00000438825, ENST00000441402, ENST00000466321, ENST00000468135, ENST00000472503, ENST00000476968, ENST00000487305, ENST00000498613, ENST00000862064, ENST00000862065, ENST00000933549, ENST00000933550, ENST00000969125, ENST00000969126

RefSeq mRNA: 4 — MANE Select: NM_018056 NM_001319677, NM_001319678, NM_001319679, NM_018056

CCDS: CCDS351

Canonical transcript exons

ENST00000336294 — 9 exons

Exon	Start	End
ENSE00001612773	32072939	32073051
ENSE00001696754	32102431	32102863
ENSE00003463525	32100442	32100562
ENSE00003547709	32074951	32075077
ENSE00003599151	32075603	32075822
ENSE00003621741	32091675	32092011
ENSE00003634453	32076763	32076846
ENSE00003640931	32077164	32077318
ENSE00003690523	32094784	32094971

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 88.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.3733 / max 190.6538, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1939	23.7603	1808
1938	1.6129	922

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.59	gold quality
monocyte	CL:0000576	86.64	gold quality
granulocyte	CL:0000094	86.53	gold quality
mononuclear cell	CL:0000842	86.49	gold quality
leukocyte	CL:0000738	86.43	gold quality
cortical plate	UBERON:0005343	85.41	gold quality
body of uterus	UBERON:0009853	84.95	gold quality
ganglionic eminence	UBERON:0004023	84.79	gold quality
stromal cell of endometrium	CL:0002255	84.74	gold quality
endocervix	UBERON:0000458	84.62	gold quality
descending thoracic aorta	UBERON:0002345	84.46	gold quality
ectocervix	UBERON:0012249	84.39	gold quality
ventricular zone	UBERON:0003053	83.89	gold quality
thoracic aorta	UBERON:0001515	83.77	gold quality
ascending aorta	UBERON:0001496	83.76	gold quality
right ovary	UBERON:0002118	83.70	gold quality
right coronary artery	UBERON:0001625	83.03	gold quality
lower esophagus mucosa	UBERON:0035834	82.88	gold quality
apex of heart	UBERON:0002098	82.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.84	gold quality
mucosa of transverse colon	UBERON:0004991	82.66	gold quality
left ovary	UBERON:0002119	82.57	gold quality
right lobe of thyroid gland	UBERON:0001119	82.49	gold quality
aorta	UBERON:0000947	82.34	gold quality
right lobe of liver	UBERON:0001114	82.16	gold quality
left coronary artery	UBERON:0001626	82.16	gold quality
left uterine tube	UBERON:0001303	81.82	gold quality
right frontal lobe	UBERON:0002810	81.81	gold quality
left lobe of thyroid gland	UBERON:0001120	81.67	gold quality
adenohypophysis	UBERON:0002196	81.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TMEM39B, 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-4425	100.00	67.59	1049
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-3165	96.18	66.22	473
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-8083	95.93	67.55	694

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem39b	ENSDARG00000018956
mus_musculus	Tmem39b	ENSMUSG00000053730
rattus_norvegicus	Tmem39b	ENSRNOG00000023746
drosophila_melanogaster	CG13016	FBGN0033899
caenorhabditis_elegans	tmem-39	WBGENE00017003

Paralogs (1): TMEM39A (ENSG00000176142)

Protein

Protein identifiers

Transmembrane protein 39B — Q9GZU3 (reviewed: Q9GZU3)

All UniProt accessions (3): Q9GZU3, F8WB89, Q5VVU5

UniProt curated annotations — full annotation on UniProt →

Function. May protect the cells against DNA damage caused by exposure to the cold-warming stress and facilitates tissue damage repair during the recovery phase.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the TMEM39 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9GZU3-1	1	yes
Q9GZU3-2	2
Q9GZU3-3	3
Q9GZU3-4	4

RefSeq proteins (4): NP_001306606, NP_001306607, NP_001306608, NP_060526* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019397	Uncharacterised_TMEM39	Family

Pfam: PF10271

UniProt features (19 total): transmembrane region 8, splice variant 6, chain 1, compositionally biased region 1, glycosylation site 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZU3-F1	74.45	0.32

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 8

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FISCHER_DREAM_TARGETS, CTTTGTA_MIR524, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, SENESE_HDAC3_TARGETS_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, chr1p35, GOCC_ORGANELLE_SUBCOMPARTMENT, GCM_DENR, BARX1_TARGET_GENES, FOXN3_TARGET_GENES, HOXB4_TARGET_GENES, HOXC6_TARGET_GENES, RBM34_TARGET_GENES, SETD7_TARGET_GENES

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (0):

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM39B	SIRAL2	Q9NWS6	522
TMEM39B	REEP6	Q96HR9	428
TMEM39B	DNAJC18	Q9H819	415
TMEM39B	GPR137C	Q8N3F9	402
TMEM39B	LETM2	Q2VYF4	399
TMEM39B	RHBDD3	Q9Y3P4	392
TMEM39B	GSG1	Q2KHT4	392
TMEM39B	TCP11L2	Q8N4U5	376
TMEM39B	MED19	A0JLT2	371
TMEM39B	PLD6	Q8N2A8	370
TMEM39B	ASXL3	Q9C0F0	360
TMEM39B	METTL26	Q96S19	360
TMEM39B	UBA5	Q9GZZ9	360
TMEM39B	STARD9	Q9P2P6	359
TMEM39B	PAQR3	Q6TCH7	353

IntAct

54 interactions, top by confidence:

A	B	Type	Score
LRFN4	RIMOC1	psi-mi:“MI:0914”(association)	0.530
SEMA7A	SGPL1	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
ADAM33	LRP5	psi-mi:“MI:0914”(association)	0.530
	UBXN8	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
IL13RA1	TMEM39B	psi-mi:“MI:0915”(physical association)	0.370
CHRNA9	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ISLR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
NRG1	HS6ST1	psi-mi:“MI:0914”(association)	0.350
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.350
PMEL	MAN1A2	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS), TMEM39B (Affinity Capture-MS)

ESM2 similar proteins: A2BD92, A4FV45, A5D7N3, A7S641, B0BN86, D3Z2R5, F1Q930, O76024, O95870, P17152, P97587, Q0IJ20, Q17QW2, Q1JPD2, Q1JPG0, Q2HJ63, Q3B8H3, Q4QQM5, Q5BK13, Q5BLE2, Q5RAS8, Q5RJQ8, Q5SWK7, Q5SYH2, Q5ZLD4, Q66H44, Q6DC66, Q6DF19, Q6GR21, Q6MG55, Q6NRI4, Q6NUQ4, Q6NWH5, Q6ZQE4, Q7L4E1, Q7SZC5, Q7ZW11, Q7ZWF4, Q7ZYA0, Q810L4

Diamond homologs: Q0IHF1, Q0VCF5, Q17QW2, Q5U2V9, Q66H44, Q6DF19, Q6GL42, Q6GNY8, Q6NRI4, Q6PH58, Q7ZW11, Q810L4, Q9CYC3, Q9GZU3, Q9NV64

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2738 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32073029:A:T	donor_gain	1.0000
1:32073047:GATGG:G	donor_gain	1.0000
1:32075077:GGTAA:G	donor_loss	1.0000
1:32075078:G:C	donor_loss	1.0000
1:32075079:T:A	donor_loss	1.0000
1:32076844:G:GT	donor_gain	1.0000
1:32077319:G:GG	donor_gain	1.0000
1:32091946:G:GT	donor_gain	1.0000
1:32092012:G:A	donor_loss	1.0000
1:32092012:G:GG	donor_gain	1.0000
1:32092013:T:A	donor_loss	1.0000
1:32094778:CCCCA:C	acceptor_loss	1.0000
1:32094779:CCCA:C	acceptor_loss	1.0000
1:32094781:CAGA:C	acceptor_loss	1.0000
1:32094782:A:AG	acceptor_gain	1.0000
1:32094782:A:G	acceptor_loss	1.0000
1:32094783:G:GG	acceptor_gain	1.0000
1:32094783:GA:G	acceptor_gain	1.0000
1:32094783:GAA:G	acceptor_gain	1.0000
1:32094783:GAAC:G	acceptor_gain	1.0000
1:32094783:GAACA:G	acceptor_gain	1.0000
1:32094969:CCC:C	donor_gain	1.0000
1:32094972:G:GG	donor_gain	1.0000
1:32100558:TCCAT:T	donor_gain	1.0000
1:32100559:CCATG:C	donor_loss	1.0000
1:32100560:CAT:C	donor_gain	1.0000
1:32100560:CATG:C	donor_loss	1.0000
1:32100561:AT:A	donor_gain	1.0000
1:32100562:TG:T	donor_loss	1.0000
1:32100563:G:GC	donor_loss	1.0000

AlphaMissense

3216 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32091917:T:C	L278P	1.000
1:32094908:C:A	A351D	1.000
1:32094917:T:C	L354P	1.000
1:32094919:G:C	G355R	1.000
1:32094920:G:A	G355D	1.000
1:32094920:G:T	G355V	1.000
1:32094925:T:A	W357R	1.000
1:32094925:T:C	W357R	1.000
1:32094926:G:C	W357S	1.000
1:32094927:G:C	W357C	1.000
1:32094927:G:T	W357C	1.000
1:32100443:T:A	W373R	1.000
1:32100443:T:C	W373R	1.000
1:32100445:G:C	W373C	1.000
1:32100445:G:T	W373C	1.000
1:32100461:T:A	W379R	1.000
1:32100461:T:C	W379R	1.000
1:32100463:G:C	W379C	1.000
1:32100463:G:T	W379C	1.000
1:32100500:T:G	Y392D	1.000
1:32100528:C:A	A401D	1.000
1:32100533:C:A	P403T	1.000
1:32100533:C:T	P403S	1.000
1:32100534:C:A	P403H	1.000
1:32100534:C:G	P403R	1.000
1:32100558:T:C	F411S	1.000
1:32091898:C:A	R272S	0.999
1:32091899:G:C	R272P	0.999
1:32091905:A:T	E274V	0.999
1:32091928:T:C	F282L	0.999

dbSNP variants (sampled 300 via entrez): RS1000041923 (1:32100347 G>A,T), RS1000075197 (1:32096747 C>T), RS1000297876 (1:32090494 C>T), RS1000314157 (1:32078445 T>C), RS1000530257 (1:32085478 C>T), RS1000566352 (1:32082975 C>A,T), RS1000601793 (1:32083982 T>G), RS1000625410 (1:32077048 G>A), RS1000626273 (1:32083991 A>C), RS1000630444 (1:32091495 C>T), RS1000825767 (1:32071319 G>A,C), RS1000890109 (1:32072907 C>T), RS1000892643 (1:32088432 A>G), RS1000932129 (1:32073820 A>G), RS1001029615 (1:32088769 C>CT,CTTTTTTTTTTTTTTTTTTTTTTT,CTTTTTTTTTTTTTTTTTTTTTTTT)

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

2 associations (top):

Study	Trait	p-value
GCST005951_36	Body mass index	9.000000e-10
GCST012038_1	Sleep duration (> 10 hours)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
bufotalin	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Asbestos, Crocidolite	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5L3	HAP1 TMEM39B (-) 2	Cancer cell line	Male
CVCL_XU52	HAP1 TMEM39B (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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