TMEM37

Summary

TMEM37 (transmembrane protein 37, HGNC:18216) is a protein-coding gene on chromosome 2q14.2, encoding Voltage-dependent calcium channel gamma-like subunit (Q8WXS4). Thought to stabilize the calcium channel in an inactivated (closed) state.

Predicted to enable calcium channel activity and voltage-gated monoatomic ion channel activity. Predicted to be involved in calcium ion transmembrane transport. Predicted to be located in membrane. Predicted to be part of monoatomic ion channel complex.

Source: NCBI Gene 140738 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_183240

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18216
Approved symbol	TMEM37
Name	transmembrane protein 37
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Aliases	PR1, PR
Ensembl gene	ENSG00000171227
Ensembl biotype	protein_coding
OMIM	618831
Entrez	140738

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000306406, ENST00000409826, ENST00000417645, ENST00000465296, ENST00000911072, ENST00000933286

RefSeq mRNA: 1 — MANE Select: NM_183240 NM_183240

CCDS: CCDS33281

Canonical transcript exons

ENST00000306406 — 2 exons

Exon	Start	End
ENSE00001022763	119436889	119438504
ENSE00001328799	119431854	119431924

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 98.58.

FANTOM5 (CAGE): breadth broad, TPM avg 6.0309 / max 344.2892, expressed in 698 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22273	5.8624	690
22272	0.1363	67
22271	0.0322	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.58	gold quality
decidua	UBERON:0002450	96.77	gold quality
adult mammalian kidney	UBERON:0000082	96.12	gold quality
mucosa of transverse colon	UBERON:0004991	96.05	gold quality
metanephros cortex	UBERON:0010533	95.73	gold quality
jejunal mucosa	UBERON:0000399	95.53	gold quality
right lobe of liver	UBERON:0001114	95.08	gold quality
liver	UBERON:0002107	93.22	gold quality
kidney	UBERON:0002113	93.22	gold quality
ileal mucosa	UBERON:0000331	92.77	gold quality
duodenum	UBERON:0002114	92.26	gold quality
renal medulla	UBERON:0000362	92.04	gold quality
adipose tissue	UBERON:0001013	91.78	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.56	gold quality
cortex of kidney	UBERON:0001225	91.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.96	gold quality
islet of Langerhans	UBERON:0000006	89.72	gold quality
metanephros	UBERON:0000081	89.37	gold quality
gall bladder	UBERON:0002110	89.00	gold quality
germinal epithelium of ovary	UBERON:0001304	88.95	gold quality
small intestine	UBERON:0002108	88.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.32	gold quality
transverse colon	UBERON:0001157	88.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.27	gold quality
nasal cavity epithelium	UBERON:0005384	88.12	gold quality
omental fat pad	UBERON:0010414	87.75	gold quality
peritoneum	UBERON:0002358	87.68	gold quality
right lobe of thyroid gland	UBERON:0001119	87.43	gold quality
pancreatic ductal cell	CL:0002079	87.28	gold quality
spleen	UBERON:0002106	87.11	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	175.32
E-MTAB-6701	yes	123.12
E-MTAB-6075	yes	94.09
E-MTAB-6678	yes	27.18
E-MTAB-5061	yes	18.09
E-GEOD-81608	yes	15.97
E-ENAD-27	yes	10.70
E-ANND-3	yes	8.54
E-CURD-10	no	115.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1

miRNA regulators (miRDB)

35 targeting TMEM37, 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-6124	99.87	69.78	3551
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-219B-5P	97.91	65.80	531
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-1224-3P	97.24	65.92	851
HSA-MIR-6860	97.21	66.31	1656

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem37	ENSDARG00000059305
mus_musculus	Tmem37	ENSMUSG00000050777
rattus_norvegicus	Tmem37	ENSRNOG00000047714

Protein

Protein identifiers

Voltage-dependent calcium channel gamma-like subunit — Q8WXS4 (reviewed: Q8WXS4)

Alternative names: Neuronal voltage-gated calcium channel gamma-like subunit, Transmembrane protein 37

All UniProt accessions (3): C9J1Q8, E7EMC0, Q8WXS4

UniProt curated annotations — full annotation on UniProt →

Function. Thought to stabilize the calcium channel in an inactivated (closed) state. Modulates calcium current when coexpressed with CACNA1G.

Subunit / interactions. The L-type calcium channel is composed of five subunits: alpha-1, alpha-2/delta, beta and gamma.

Subcellular location. Membrane.

Similarity. Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.

RefSeq proteins (1): NP_899063* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029372	Tmem37	Family

Pfam: PF15108

UniProt features (7 total): transmembrane region 4, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXS4-F1	87.00	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): ZHAN_MULTIPLE_MYELOMA_MF_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, GOLDRATH_ANTIGEN_RESPONSE, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GGARNTKYCCA_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, HNF1_C, BASAKI_YBX1_TARGETS_DN, BURTON_ADIPOGENESIS_10, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, ACEVEDO_LIVER_CANCER_UP, RIGGI_EWING_SARCOMA_PROGENITOR_UP, chr2q14, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (4): monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), monoatomic ion transmembrane transport (GO:0034220), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (2): voltage-gated monoatomic ion channel activity (GO:0005244), calcium channel activity (GO:0005262)

GO Cellular Component (2): monoatomic ion channel complex (GO:0034702), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic ion channel activity	1
voltage-gated channel activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM37	PRTN3	P15637	789
TMEM37	MAGEH1	Q9H213	591
TMEM37	NPR1	P16066	571
TMEM37	GLIPR2	Q9H4G4	540
TMEM37	CRISP2	P16562	527
TMEM37	CRISP1	P54107	527
TMEM37	TMEFF2	Q9UIK5	492
TMEM37	PHF12	Q96QT6	479
TMEM37	SCTR	P47872	444
TMEM37	TXK	P42681	437
TMEM37	CRISP3	P54108	418
TMEM37	GLIPR1	P48060	405
TMEM37	EEIG2	Q5T8I3	405
TMEM37	CHIT1	Q13231	400
TMEM37	ANKRD23	Q86SG2	392

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MPP3	TMEM37	psi-mi:“MI:0915”(physical association)	0.370
SPIB	TMEM37	psi-mi:“MI:0915”(physical association)	0.370
TMEM37	PLA2G12A	psi-mi:“MI:0915”(physical association)	0.370
TMEM37	ORM1	psi-mi:“MI:0915”(physical association)	0.370
HBP1	TMEM37	psi-mi:“MI:0915”(physical association)	0.370
UBQLN1	TMEM37	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (12): TMEM37 (Affinity Capture-RNA), TMEM37 (Co-fractionation), TMEM37 (Co-fractionation), TMEM37 (Co-fractionation), TMEM37 (Co-fractionation), TMEM37 (Co-fractionation), TMEM37 (Two-hybrid), TMEM37 (Two-hybrid), TMEM37 (Two-hybrid), TMEM37 (Two-hybrid), TMEM37 (Two-hybrid), UBQLN1 (Two-hybrid)

ESM2 similar proteins: A4IIU3, A6NML5, D3YWQ9, O75204, P0DP42, P11836, P20490, P56749, Q01362, Q0IIL2, Q2KJ11, Q2YDM3, Q32KQ5, Q3T110, Q3YBM2, Q497B3, Q4G068, Q504G0, Q5EB63, Q5FWC3, Q5HYL7, Q5M962, Q5R8D6, Q5R9K1, Q5RCD5, Q5RFC1, Q6GV28, Q7T392, Q7TQI0, Q7YQI4, Q8BGP5, Q8BHH8, Q8C6V3, Q8K177, Q8NCR9, Q8VHW1, Q8WXS4, Q920C4, Q925D4, Q940P5

Diamond homologs: Q8VHW1, Q8WXS4, Q9JJV3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

316 predictions. Top by Δscore:

Variant	Effect	Δscore
2:119431920:TGCAG:T	donor_loss	0.9900
2:119431921:GCAGG:G	donor_loss	0.9900
2:119431922:CAGGT:C	donor_loss	0.9900
2:119431924:GGTAG:G	donor_loss	0.9900
2:119431925:GTAGC:G	donor_loss	0.9900
2:119431926:T:G	donor_loss	0.9900
2:119436884:TCCA:T	acceptor_loss	0.9900
2:119436885:CCA:C	acceptor_loss	0.9900
2:119436887:A:AG	acceptor_gain	0.9900
2:119436887:A:C	acceptor_loss	0.9900
2:119436887:AGGCC:A	acceptor_gain	0.9900
2:119436888:G:GG	acceptor_gain	0.9900
2:119436888:GGCCC:G	acceptor_gain	0.9900
2:119431922:C:T	donor_gain	0.9800
2:119436876:C:CA	acceptor_gain	0.9800
2:119436885:CCAGG:C	acceptor_gain	0.9800
2:119436886:CAGG:C	acceptor_gain	0.9800
2:119436887:AG:A	acceptor_gain	0.9800
2:119436888:GG:G	acceptor_gain	0.9800
2:119436888:GGC:G	acceptor_gain	0.9800
2:119436888:GGCC:G	acceptor_gain	0.9800
2:119436877:G:A	acceptor_gain	0.9600
2:119431974:G:T	donor_gain	0.9500
2:119431974:G:GT	donor_gain	0.9300
2:119431960:C:CG	donor_gain	0.9200
2:119432211:A:T	donor_gain	0.9000
2:119431920:TGC:T	donor_gain	0.8900
2:119436884:TCCAG:T	acceptor_gain	0.8900
2:119436318:A:AG	acceptor_gain	0.8700
2:119436319:G:GG	acceptor_gain	0.8700

AlphaMissense

1238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:119437351:T:C	F162L	0.965
2:119437353:T:A	F162L	0.965
2:119437353:T:G	F162L	0.965
2:119437300:T:C	F145L	0.955
2:119437302:T:A	F145L	0.955
2:119437302:T:G	F145L	0.955
2:119437399:A:C	S178R	0.939
2:119437401:C:A	S178R	0.939
2:119437401:C:G	S178R	0.939
2:119437017:G:C	W50C	0.938
2:119437017:G:T	W50C	0.938
2:119437354:T:A	W163R	0.927
2:119437354:T:C	W163R	0.927
2:119437015:T:A	W50R	0.919
2:119437015:T:C	W50R	0.919
2:119437050:G:C	W61C	0.919
2:119437050:G:T	W61C	0.919
2:119437270:T:C	F135L	0.913
2:119437272:C:A	F135L	0.913
2:119437272:C:G	F135L	0.913
2:119437039:T:C	F58L	0.907
2:119437041:C:A	F58L	0.907
2:119437041:C:G	F58L	0.907
2:119437246:G:C	G127R	0.889
2:119437352:T:C	F162S	0.884
2:119437363:T:C	F166L	0.882
2:119437365:C:A	F166L	0.882
2:119437365:C:G	F166L	0.882
2:119437384:T:C	F173L	0.874
2:119437386:C:A	F173L	0.874

dbSNP variants (sampled 300 via entrez): RS1000027808 (2:119430483 G>A,C), RS1000441352 (2:119430830 G>A), RS1001035386 (2:119428363 C>T), RS1001279859 (2:119435814 C>A,G), RS1001291277 (2:119436089 C>G,T), RS1001526029 (2:119430173 G>A), RS1001702811 (2:119430997 G>A), RS1001891795 (2:119429943 G>A,T), RS1002167184 (2:119435401 C>T), RS1002272780 (2:119431533 T>C), RS1002439802 (2:119429721 A>C), RS1002893671 (2:119438086 C>A,T), RS1003118647 (2:119431979 TG>T), RS1003225742 (2:119436905 G>A), RS1003624499 (2:119434428 G>C,T)

Disease associations

OMIM: gene MIM:618831 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment, increases expression	5
Benzo(a)pyrene	decreases expression, increases methylation	4
Cyclosporine	decreases expression	4
bisphenol A	increases expression, increases methylation, affects expression, decreases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Cadmium	decreases expression	2
Calcitriol	increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
propionaldehyde	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
sulforaphane	increases expression	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
ormosil	decreases expression, affects binding	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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