TMEM59L

Summary

TMEM59L (transmembrane protein 59 like, HGNC:13237) is a protein-coding gene on chromosome 19p13.11, encoding Transmembrane protein 59-like (Q9UK28). Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of APP.

This gene encodes a predicted type-I membrane glycoprotein. The encoded protein may play a role in functioning of the central nervous system.

Source: NCBI Gene 25789 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_012109

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13237
Approved symbol	TMEM59L
Name	transmembrane protein 59 like
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	BSMAP
Ensembl gene	ENSG00000105696
Ensembl biotype	protein_coding
OMIM	617096
Entrez	25789

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 retained_intron

ENST00000262817, ENST00000594709, ENST00000594859, ENST00000598660, ENST00000600490, ENST00000897894, ENST00000897895, ENST00000897896, ENST00000929592, ENST00000929593, ENST00000946166, ENST00000946167

RefSeq mRNA: 1 — MANE Select: NM_012109 NM_012109

CCDS: CCDS12383

Canonical transcript exons

ENST00000262817 — 8 exons

Exon	Start	End
ENSE00000866205	18612870	18613129
ENSE00003474305	18613872	18614016
ENSE00003550844	18617000	18617102
ENSE00003624985	18615975	18616127
ENSE00003649036	18614104	18614195
ENSE00003889597	18620408	18621039
ENSE00003893290	18618375	18618492
ENSE00003896168	18618155	18618272

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4535 / max 772.7766, expressed in 959 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174707	18.5912	942
174708	1.4498	170
174709	0.2752	119
174703	0.0779	27
174702	0.0447	16
174704	0.0148	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.43	gold quality
right frontal lobe	UBERON:0002810	99.36	gold quality
cerebellar hemisphere	UBERON:0002245	99.32	gold quality
cerebellar cortex	UBERON:0002129	99.29	gold quality
anterior cingulate cortex	UBERON:0009835	98.74	gold quality
cingulate cortex	UBERON:0003027	98.73	gold quality
prefrontal cortex	UBERON:0000451	98.41	gold quality
nucleus accumbens	UBERON:0001882	98.38	gold quality
amygdala	UBERON:0001876	98.17	gold quality
cerebellum	UBERON:0002037	98.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.70	gold quality
caudate nucleus	UBERON:0001873	97.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.46	gold quality
cortical plate	UBERON:0005343	97.37	gold quality
putamen	UBERON:0001874	97.02	gold quality
frontal cortex	UBERON:0001870	96.80	gold quality
frontal lobe	UBERON:0016525	96.80	gold quality
neocortex	UBERON:0001950	96.60	gold quality
adenohypophysis	UBERON:0002196	96.58	gold quality
hypothalamus	UBERON:0001898	95.74	gold quality
telencephalon	UBERON:0001893	95.53	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.50	gold quality
forebrain	UBERON:0001890	95.40	gold quality
pituitary gland	UBERON:0000007	95.31	gold quality
cerebral cortex	UBERON:0000956	95.21	gold quality
brain	UBERON:0000955	95.18	gold quality
cerebellar vermis	UBERON:0004720	94.39	gold quality
Ammon’s horn	UBERON:0001954	94.00	gold quality
temporal lobe	UBERON:0001871	93.38	gold quality
ganglionic eminence	UBERON:0004023	92.52	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	249.06
E-GEOD-84465	yes	6.81
E-ANND-3	yes	3.44
E-HCAD-5	no	2.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting TMEM59L, 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-1252-5P	100.00	69.80	2774
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-3943	95.87	64.57	523
HSA-MIR-6789-5P	94.05	66.19	285
HSA-MIR-4781-5P	88.22	64.40	100

Literature-anchored findings (GeneRIF, showing 1)

• Expression of TMEM59L associated with radiosensitive in glioblastoma. (PMID:37439405)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem59l	ENSDARG00000003655
mus_musculus	Tmem59l	ENSMUSG00000035964
rattus_norvegicus	Tmem59l	ENSRNOG00000022432

Paralogs (1): TMEM59 (ENSG00000116209)

Protein

Protein identifiers

Transmembrane protein 59-like — Q9UK28 (reviewed: Q9UK28)

Alternative names: Brain-specific membrane-anchored protein

All UniProt accessions (2): Q9UK28, M0R134

UniProt curated annotations — full annotation on UniProt →

Function. Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of APP. Inhibits APP transport to the cell surface and further shedding.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Expressed preferentially at high level in the brain.

Similarity. Belongs to the TMEM59 family.

RefSeq proteins (1): NP_036241* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022065	Uncharacterised_TMEM59	Family

Pfam: PF12280

UniProt features (5 total): signal peptide 1, chain 1, transmembrane region 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK28-F1	61.70	0.11

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): 97

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 120 (showing top): ATF_B, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GAANYNYGACNY_UNKNOWN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CREBP1_Q2, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, CREB_Q4, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_NEPHRON_EPITHELIUM_DEVELOPMENT, MYCMAX_01, ROZANOV_MMP14_TARGETS_UP, GOBP_RENAL_TUBULE_DEVELOPMENT, GOBP_MESONEPHRIC_TUBULE_MORPHOGENESIS

GO Biological Process (1): branching involved in ureteric bud morphogenesis (GO:0001658)

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

GO Cellular Component (3): Golgi membrane (GO:0000139), membrane (GO:0016020), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

4366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM59L	TOR4A	Q9NXH8	522
TMEM59L	TMEM101	Q96IK0	486
TMEM59L	TMEM208	Q9BTX3	475
TMEM59L	PSD2	Q9BQI7	474
TMEM59L	KXD1	Q9BQD3	466
TMEM59L	TMEM115	Q12893	445
TMEM59L	TRARG1	Q8IXB3	424
TMEM59L	TMEM278	A6NKF7	377
TMEM59L	ANKRD45	Q5TZF3	376
TMEM59L	NCKAP5L	Q9HCH0	373
TMEM59L	TMEM145	Q8NBT3	371
TMEM59L	TMEM178A	Q8NBL3	365
TMEM59L	ENTREP2	O60320	360
TMEM59L	FAM81A	Q8TBF8	344
TMEM59L	TMEM11	P17152	344

IntAct

57 interactions, top by confidence:

A	B	Type	Score
ITM2B	TMEM59L	psi-mi:“MI:0915”(physical association)	0.620
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CD1E	SUSD5	psi-mi:“MI:0914”(association)	0.530
GABRA3	HLA-C	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
YAP1	TMEM59L	psi-mi:“MI:0407”(direct interaction)	0.440
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PCDHGB4	FAM171A2	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
GABRA3	GPAA1	psi-mi:“MI:0914”(association)	0.350
HTR3A	GPAA1	psi-mi:“MI:0914”(association)	0.350
ATP1B4	RTN2	psi-mi:“MI:0914”(association)	0.350
ITM2B	SEMA4F	psi-mi:“MI:0914”(association)	0.350
MUC1	TNFSF9	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
CDH5	NBAS	psi-mi:“MI:0914”(association)	0.350
GINM1	FAM234B	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
CRLF2	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
HTR3C	GET1	psi-mi:“MI:0914”(association)	0.350
PCDHB1	GOLIM4	psi-mi:“MI:0914”(association)	0.350
ABHD14A	NDUFA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), TMEM59L (Proximity Label-MS)

ESM2 similar proteins: A0A096P2H6, A0A0D9S1R4, A2APA5, A9CBA0, P06740, P06759, P0DKU6, P0DKW1, P0DKW2, P0DKW3, P0DKW4, P0DKY3, P0DML4, P0DML5, P0DML6, P0DMN8, P0DOC4, P0DP53, P0DTG9, P0DTH0, P0DTH1, P0DTH2, P0DTH3, P0DTH4, P0DUP5, P0DUP6, P22749, P33622, P35225, P55056, P55057, P55797, Q0VCT2, Q13790, Q3SYR5, Q3ZRW9, Q5HZE8, Q5JTB6, Q5JX69, Q5JX71

Diamond homologs: Q0VCT2, Q2F7Z7, Q3T0Q2, Q4R8C8, Q5HZE8, Q5R800, Q7TNI2, Q9BXS4, Q9QY73, Q9UK28

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
adaptive immune response	7	8.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1643 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18613870:AGGC:A	acceptor_gain	1.0000
19:18613870:AGGCG:A	acceptor_gain	1.0000
19:18613871:GGCG:G	acceptor_gain	1.0000
19:18613871:GGCGG:G	acceptor_gain	1.0000
19:18614102:A:AG	acceptor_gain	1.0000
19:18614103:G:GG	acceptor_gain	1.0000
19:18614103:GCCT:G	acceptor_gain	1.0000
19:18616992:T:A	acceptor_gain	1.0000
19:18618244:G:GT	donor_gain	1.0000
19:18620404:GCA:G	acceptor_loss	1.0000
19:18620405:CA:C	acceptor_loss	1.0000
19:18620406:A:AC	acceptor_loss	1.0000
19:18620406:A:AG	acceptor_gain	1.0000
19:18620407:G:GG	acceptor_gain	1.0000
19:18620407:GC:G	acceptor_gain	1.0000
19:18620407:GCC:G	acceptor_gain	1.0000
19:18620407:GCCT:G	acceptor_gain	1.0000
19:18620407:GCCTC:G	acceptor_gain	1.0000
19:18613128:AG:A	donor_loss	0.9900
19:18613129:GGTGA:G	donor_loss	0.9900
19:18613130:G:A	donor_loss	0.9900
19:18613131:T:G	donor_loss	0.9900
19:18613870:A:AG	acceptor_gain	0.9900
19:18613871:G:GA	acceptor_gain	0.9900
19:18613871:GGC:G	acceptor_gain	0.9900
19:18614013:GCAG:G	donor_gain	0.9900
19:18614099:CACA:C	acceptor_loss	0.9900
19:18614102:A:G	acceptor_loss	0.9900
19:18614103:G:A	acceptor_loss	0.9900
19:18614103:GC:G	acceptor_gain	0.9900

AlphaMissense

2202 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18614007:T:A	C103S	0.998
19:18614008:G:C	C103S	0.998
19:18614107:G:A	C107Y	0.998
19:18613938:G:T	G80C	0.997
19:18614009:T:G	C103W	0.997
19:18614108:C:G	C107W	0.997
19:18614146:G:A	C120Y	0.997
19:18614147:T:G	C120W	0.997
19:18616080:T:A	W172R	0.997
19:18616080:T:C	W172R	0.997
19:18613939:G:A	G80D	0.996
19:18613941:T:A	C81S	0.996
19:18613942:G:C	C81S	0.996
19:18613961:C:G	C87W	0.996
19:18613965:T:C	F89L	0.996
19:18613966:T:G	F89C	0.996
19:18613967:T:A	F89L	0.996
19:18613967:T:G	F89L	0.996
19:18614008:G:A	C103Y	0.996
19:18614008:G:T	C103F	0.996
19:18614106:T:C	C107R	0.996
19:18614145:T:A	C120S	0.996
19:18614146:G:C	C120S	0.996
19:18616123:T:C	F186S	0.996
19:18618394:T:A	W268R	0.996
19:18618394:T:C	W268R	0.996
19:18618409:T:C	C273R	0.996
19:18618445:A:C	S285R	0.996
19:18618447:C:A	S285R	0.996
19:18618447:C:G	S285R	0.996

dbSNP variants (sampled 300 via entrez): RS1000003772 (19:18617638 T>C), RS1001788715 (19:18612571 G>A,C), RS1002170289 (19:18616958 T>C), RS1002222721 (19:18616649 T>A), RS1002391639 (19:18611041 C>G,T), RS1002495431 (19:18621336 A>G), RS1002928648 (19:18619197 A>C), RS1002941330 (19:18614462 A>C), RS1002975242 (19:18619875 A>T), RS1003059620 (19:18613419 C>G,T), RS1003158924 (19:18619806 A>G), RS1003482821 (19:18621512 A>G), RS1004287035 (19:18617018 A>C), RS1004588031 (19:18611102 C>T), RS1005062139 (19:18621259 C>G,T)

Disease associations

OMIM: gene MIM:617096 | 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
GCST008832_21	Gastroesophageal reflux disease	2.000000e-09
GCST010320_32	PR interval	2.000000e-09
GCST010321_91	PR interval	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
kojic acid	decreases expression	1
terbufos	increases methylation	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases response to substance	1
Acetaminophen	increases expression	1
Arbutin	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Fonofos	increases methylation	1
Folic Acid	decreases expression	1
Lead	affects expression	1
Parathion	increases methylation	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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