TMEM203

Summary

TMEM203 (transmembrane protein 203, HGNC:28217) is a protein-coding gene on chromosome 9q34.3, encoding Transmembrane protein 203 (Q969S6). Involved in the regulation of cellular calcium homeotasis.

Involved in intracellular calcium ion homeostasis. Located in endoplasmic reticulum.

Source: NCBI Gene 94107 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total — 1 pathogenic
• MANE Select transcript: NM_053045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28217
Approved symbol	TMEM203
Name	transmembrane protein 203
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC14327, HBEBP1
Ensembl gene	ENSG00000187713
Ensembl biotype	protein_coding
OMIM	616499
Entrez	94107

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000343666

RefSeq mRNA: 1 — MANE Select: NM_053045 NM_053045

CCDS: CCDS35185

Canonical transcript exons

ENST00000343666 — 1 exons

Exon	Start	End
ENSE00001374176	137204082	137205648

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1709 / max 78.3085, expressed in 1803 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103330	14.1709	1803

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	93.40	gold quality
heart left ventricle	UBERON:0002084	92.69	gold quality
gastrocnemius	UBERON:0001388	91.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.75	gold quality
mucosa of transverse colon	UBERON:0004991	91.74	gold quality
muscle of leg	UBERON:0001383	91.69	gold quality
skin of leg	UBERON:0001511	91.50	gold quality
heart	UBERON:0000948	91.39	gold quality
prefrontal cortex	UBERON:0000451	91.35	gold quality
zone of skin	UBERON:0000014	91.25	gold quality
granulocyte	CL:0000094	91.17	gold quality
skin of abdomen	UBERON:0001416	91.17	gold quality
right lobe of liver	UBERON:0001114	91.10	gold quality
frontal cortex	UBERON:0001870	91.06	gold quality
right frontal lobe	UBERON:0002810	90.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.85	gold quality
right atrium auricular region	UBERON:0006631	90.72	gold quality
putamen	UBERON:0001874	90.70	gold quality
cerebral cortex	UBERON:0000956	90.66	gold quality
right adrenal gland cortex	UBERON:0035827	90.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.59	gold quality
anterior cingulate cortex	UBERON:0009835	90.52	gold quality
right adrenal gland	UBERON:0001233	90.42	gold quality
nucleus accumbens	UBERON:0001882	90.40	gold quality
fundus of stomach	UBERON:0001160	90.29	gold quality
left adrenal gland	UBERON:0001234	90.20	gold quality
caudate nucleus	UBERON:0001873	90.20	gold quality
adult mammalian kidney	UBERON:0000082	90.12	gold quality
cortical plate	UBERON:0005343	90.08	gold quality
lower esophagus	UBERON:0013473	89.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	82.39
E-ANND-3	yes	5.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting TMEM203, 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-3120-5P	100.00	65.56	965
HSA-MIR-6888-3P	99.97	65.95	1170
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-6715A-3P	99.83	68.05	1473
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-941	79.36	58.80	51

Literature-anchored findings (GeneRIF, showing 2)

• Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis and provides a causal link between intracellular calcium regulation and spermiogenesis. (PMID:25996873)
• Identification of TMEM203 sheds light into the control of STING-mediated innate immune responses. (PMID:31346090)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem203	ENSDARG00000104996
mus_musculus	Tmem203	ENSMUSG00000078201
rattus_norvegicus	Tmem203	ENSRNOG00000072261
drosophila_melanogaster	CG33932	FBGN0066303

Protein

Protein identifiers

Transmembrane protein 203 — Q969S6 (reviewed: Q969S6)

All UniProt accessions (1): Q969S6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of cellular calcium homeotasis. Required for spermatogenesis. Acts as a regulator of STING-mediated inflammatory signaling in macrophages. Forms a complex with STING, promoting the activity of TBK1 kinase and the transcription factor IRF3, leading to activation of type I interferon expression.

Subunit / interactions. Homodimer. Interacts with ATP2A2, ITPR3 and STIM1. Interacts with STING1 (via transmembrane domain).

Subcellular location. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment. Lysosome membrane.

Tissue specificity. Increased expression seen in T-lymphocytes from patients with systemic lupus erythematosus (SLE).

RefSeq proteins (1): NP_444273* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019396	TM_Fragile-X-F-assoc	Family

UniProt features (8 total): transmembrane region 4, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969S6-F1	84.89	0.34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): GOCC_VACUOLAR_MEMBRANE, GOBP_MALE_GAMETE_GENERATION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, WHN_B, GOBP_HOMEOSTATIC_PROCESS, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_CHEMICAL_HOMEOSTASIS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ENDOPLASMIC_RETICULUM_GOLGI_INTERMEDIATE_COMPARTMENT, GOCC_ORGANELLE_SUBCOMPARTMENT, NUYTTEN_NIPP1_TARGETS_DN, chr9q34, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNAR_KO_UP, GSE14415_NATURAL_TREG_VS_TCONV_UP

GO Biological Process (2): intracellular calcium ion homeostasis (GO:0006874), spermatogenesis (GO:0007283)

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

GO Cellular Component (6): lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), lysosome (GO:0005764), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
developmental process involved in reproduction	1
male gamete generation	1
binding	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM203	SNX8	Q9Y5X2	488
TMEM203	STIM1	Q13586	392
TMEM203	ANKLE2	Q86XL3	390
TMEM203	TMEM120A	Q9BXJ8	362
TMEM203	TMEM185B	Q9H7F4	360
TMEM203	SLC35G1	Q2M3R5	349
TMEM203	TMEM60	Q9H2L4	348
TMEM203	TRMT5	Q32P41	347
TMEM203	FMC1	Q96HJ9	347
TMEM203	SETD4	Q9NVD3	347
TMEM203	ATG9A	Q7Z3C6	327
TMEM203	TMEM185A	Q8NFB2	321
TMEM203	CDPF1	Q6NVV7	312
TMEM203	POP7	O75817	309
TMEM203	SSR2	P43308	307
TMEM203	NDOR1	Q9UHB4	307

IntAct

113 interactions, top by confidence:

A	B	Type	Score
TMEM203	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	TMX2	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	RMDN3	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	TMEM234	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	ATP6AP2	psi-mi:“MI:0915”(physical association)	0.560
STX4	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
MFSD5	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
CNR2	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
CPLX4	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
SSMEM1	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
ANK1	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
FAM174A	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
STOM	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	MANBAL	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
RETREG3	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
EBP	TMEM203	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (44): TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid), TMEM203 (Two-hybrid)

ESM2 similar proteins: A2AF53, A4K2N5, A4K2W1, O75915, P51811, Q08DE2, Q1RMQ3, Q3SYY9, Q3ZBX1, Q49LS5, Q4R4R4, Q4R5E3, Q56P28, Q58DA4, Q58E26, Q5BJW3, Q5E9M1, Q5F3F5, Q5GH61, Q5PQQ4, Q5PR61, Q5R4X8, Q5R8H8, Q5R9W1, Q5ZI05, Q5ZII3, Q62302, Q68DH5, Q6AZ61, Q6P4P2, Q6UWH6, Q78S06, Q7SYC7, Q7ZUA6, Q8C561, Q8K0B2, Q8N2H4, Q8NFB2, Q8R235, Q8R3R5

Diamond homologs: Q5XH84, Q6GNX5, Q8R235, Q969S6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2627632	NM_001128228.3(TPRN):c.301G>T (p.Glu101Ter)	Pathogenic

SpliceAI

303 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137205142:CAGG:C	donor_gain	0.8200
9:137205143:AGGA:A	donor_gain	0.8200
9:137205599:AAC:A	donor_gain	0.8000
9:137205034:CAG:C	acceptor_gain	0.7300
9:137205037:C:CC	acceptor_gain	0.7300
9:137205033:GCAG:G	acceptor_gain	0.7100
9:137205034:CAGC:C	acceptor_gain	0.7100
9:137205035:AG:A	acceptor_gain	0.6900
9:137205600:A:C	donor_gain	0.6700
9:137205194:T:TA	donor_gain	0.6500
9:137205598:CA:C	donor_gain	0.6500
9:137205599:AA:A	donor_gain	0.6500
9:137205035:AGC:A	acceptor_loss	0.6300
9:137205036:GCT:G	acceptor_loss	0.6300
9:137205037:C:T	acceptor_loss	0.6300
9:137205038:T:A	acceptor_loss	0.6300
9:137205039:G:C	acceptor_loss	0.6100
9:137204381:TTGG:T	acceptor_gain	0.6000
9:137205047:A:C	acceptor_loss	0.6000
9:137204688:T:C	donor_gain	0.5900
9:137205272:TTCC:T	donor_gain	0.5900
9:137205032:AGCAG:A	acceptor_gain	0.5800
9:137205274:C:CT	donor_gain	0.5300
9:137204687:A:AC	donor_gain	0.5200
9:137205143:AGGAC:A	donor_gain	0.5200
9:137205386:TG:T	donor_gain	0.5200
9:137204600:T:A	donor_gain	0.4900
9:137204777:A:C	acceptor_gain	0.4900
9:137205135:TGAG:T	donor_gain	0.4900
9:137205084:C:CA	donor_gain	0.4800

AlphaMissense

867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137205139:A:C	S92R	0.995
9:137205139:A:T	S92R	0.995
9:137205141:T:G	S92R	0.995
9:137205242:C:T	G58E	0.983
9:137205384:A:G	W11R	0.983
9:137205384:A:T	W11R	0.983
9:137205049:G:C	F122L	0.981
9:137205049:G:T	F122L	0.981
9:137205051:A:G	F122L	0.981
9:137205260:G:C	P52R	0.980
9:137205056:G:C	P120R	0.979
9:137205056:G:T	P120Q	0.979
9:137205218:A:T	I66N	0.979
9:137205235:G:C	S60R	0.979
9:137205235:G:T	S60R	0.979
9:137205237:T:G	S60R	0.979
9:137205176:G:T	A80E	0.971
9:137205137:A:T	L93H	0.970
9:137205243:C:G	G58R	0.970
9:137205243:C:T	G58R	0.970
9:137205363:C:T	E18K	0.968
9:137205072:C:G	G115R	0.967
9:137205050:A:G	F122S	0.966
9:137205047:A:T	I123N	0.965
9:137205251:G:T	A55D	0.964
9:137205260:G:T	P52H	0.964
9:137205362:T:A	E18V	0.964
9:137205207:G:T	R70S	0.963
9:137205248:G:T	A56D	0.963
9:137205253:G:C	F54L	0.963

dbSNP variants (sampled 300 via entrez): RS1000316314 (9:137205948 G>A), RS1001913493 (9:137205120 T>C), RS1001986964 (9:137204743 T>A), RS1002966087 (9:137206627 C>A,T), RS1003091122 (9:137206889 G>A,T), RS1004095692 (9:137206362 G>A,T), RS1004339209 (9:137203888 G>A,C,T), RS1006128815 (9:137203853 T>C), RS1007013110 (9:137204934 GC>G), RS1007250234 (9:137205713 C>T), RS1007799023 (9:137206895 A>G), RS1008520183 (9:137204352 A>C,G), RS1009099395 (9:137207305 C>G,T), RS1009693603 (9:137204384 G>A,C), RS1010471773 (9:137205895 C>G,T)

Disease associations

OMIM: gene MIM:616499 | disease phenotypes: MIM:613307

GenCC curated gene-disease

Mondo (1): autosomal recessive nonsyndromic hearing loss 79 (MONDO:0013215)

Orphanet (1): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567651	Deafness, Autosomal Recessive 79 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Silver	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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