TMEM50A

Summary

TMEM50A (transmembrane protein 50A, HGNC:30590) is a protein-coding gene on chromosome 1p36.11, encoding Transmembrane protein 50A (O95807).

This gene is located in the RH gene locus, between the RHD and RHCE genes. The function of its protein product is unknown; however, its sequence has potential transmembrane domains suggesting that it may be an integral membrane protein. Its position between the RH genes suggests that polymorphisms in this gene may be tightly linked to RH haplotypes and may contribute to selective pressure for or against certain RH haplotypes.

Source: NCBI Gene 23585 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_014313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30590
Approved symbol	TMEM50A
Name	transmembrane protein 50A
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	SMP1
Ensembl gene	ENSG00000183726
Ensembl biotype	protein_coding
OMIM	605348
Entrez	23585

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000374358, ENST00000468704, ENST00000480937, ENST00000487234, ENST00000491936, ENST00000498135, ENST00000905338, ENST00000905339, ENST00000905340, ENST00000905341, ENST00000915351, ENST00000951033, ENST00000951034, ENST00000951035

RefSeq mRNA: 1 — MANE Select: NM_014313 NM_014313

CCDS: CCDS264

Canonical transcript exons

ENST00000374358 — 7 exons

Exon	Start	End
ENSE00001463261	25360660	25362361
ENSE00001950898	25338334	25338456
ENSE00003505699	25352882	25352974
ENSE00003531275	25342961	25343073
ENSE00003542781	25340474	25340579
ENSE00003550196	25356793	25356853
ENSE00003682604	25351626	25351693

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 131.0831 / max 842.0722, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1496	130.4941	1828
1497	0.5890	290

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	98.96	gold quality
monocyte	CL:0000576	98.91	gold quality
mononuclear cell	CL:0000842	98.73	gold quality
leukocyte	CL:0000738	98.66	gold quality
epithelium of nasopharynx	UBERON:0001951	98.54	gold quality
palpebral conjunctiva	UBERON:0001812	98.37	gold quality
pericardium	UBERON:0002407	98.21	gold quality
parotid gland	UBERON:0001831	98.06	gold quality
gingiva	UBERON:0001828	97.90	gold quality
corpus epididymis	UBERON:0004359	97.84	gold quality
mammary duct	UBERON:0001765	97.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.68	gold quality
gingival epithelium	UBERON:0001949	97.67	gold quality
germinal epithelium of ovary	UBERON:0001304	97.66	gold quality
colonic mucosa	UBERON:0000317	97.55	gold quality
vena cava	UBERON:0004087	97.53	gold quality
cortical plate	UBERON:0005343	97.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.51	gold quality
left adrenal gland	UBERON:0001234	97.50	gold quality
right adrenal gland cortex	UBERON:0035827	97.50	gold quality
right adrenal gland	UBERON:0001233	97.48	gold quality
adrenal cortex	UBERON:0001235	97.45	gold quality
left adrenal gland cortex	UBERON:0035825	97.38	gold quality
saphenous vein	UBERON:0007318	97.35	gold quality
cauda epididymis	UBERON:0004360	97.34	gold quality
caput epididymis	UBERON:0004358	97.32	gold quality
oral cavity	UBERON:0000167	97.31	gold quality
pylorus	UBERON:0001166	97.31	gold quality
rectum	UBERON:0001052	97.30	gold quality
calcaneal tendon	UBERON:0003701	97.28	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	16.49
E-MTAB-6701	yes	14.81
E-CURD-46	yes	10.55
E-CURD-112	yes	9.14
E-MTAB-7052	no	453.19
E-MTAB-10290	no	316.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

91 targeting TMEM50A, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-323A-3P	99.79	70.30	1739

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem50a	ENSDARG00000015757
mus_musculus	Tmem50a	ENSMUSG00000028822
rattus_norvegicus	Tmem50a	ENSRNOG00000017279
drosophila_melanogaster	CG15012	FBGN0035528
caenorhabditis_elegans	Y74C10AL.2	WBGENE00022280

Paralogs (1): TMEM50B (ENSG00000142188)

Protein

Protein identifiers

Transmembrane protein 50A — O95807 (reviewed: O95807)

Alternative names: Small membrane protein 1

All UniProt accessions (3): B7Z5M7, O95807, Q7RU07

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the UPF0220 family.

RefSeq proteins (1): NP_055128* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007919	UPF0220	Family

Pfam: PF05255

UniProt features (10 total): transmembrane region 4, modified residue 2, sequence variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95807-F1	83.15	0.46

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 (2): 2, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MULTIVESICULAR_BODY_SORTING_PATHWAY, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, WANG_RESPONSE_TO_FORSKOLIN_UP, WANG_RESPONSE_TO_ANDROGEN_UP, AIYAR_COBRA1_TARGETS_UP, GOCC_GLIAL_CELL_PROJECTION, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOCC_CELL_BODY, GOCC_SOMATODENDRITIC_COMPARTMENT

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 (5): endoplasmic reticulum (GO:0005783), membrane (GO:0016020), neuronal cell body (GO:0043025), glial cell projection (GO:0097386), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
endosome transport via multivesicular body sorting pathway	1
late endosome to vacuole transport	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
somatodendritic compartment	1
cell body	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM50A	RHCE	P18577	948
TMEM50A	RSRP1	Q9BUV0	674
TMEM50A	SERTAD3	Q9UJW9	580
TMEM50A	MACO1	Q8N5G2	547
TMEM50A	TMEM253	P0C7T8	545
TMEM50A	SYF2	O95926	513
TMEM50A	NPEPPS	P55786	493
TMEM50A	YBX3	P16989	489
TMEM50A	BRD3OS	A0A1B0GUI7	470
TMEM50A	BID	P55957	462
TMEM50A	CYSRT1	A8MQ03	447
TMEM50A	NOXRED1	Q6NXP6	447
TMEM50A	PBLD	P30039	425
TMEM50A	MTPAP	Q9NVV4	415
TMEM50A	SLC10A5	Q5PT55	404

IntAct

38 interactions, top by confidence:

A	B	Type	Score
ABCG4	TMEM50A	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	SYT9	psi-mi:“MI:0915”(physical association)	0.560
	TMEM50A	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	COMT	psi-mi:“MI:0915”(physical association)	0.560
LEPROT	TMEM50A	psi-mi:“MI:0915”(physical association)	0.560
LEPROTL1	TMEM50A	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	ABCG4	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	AQP6	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	HLA-DPA1	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	SLC30A8	psi-mi:“MI:0915”(physical association)	0.560
TMEM50A	REEP4	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
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM50A		psi-mi:“MI:0915”(physical association)	0.000
COMT	TMEM50A	psi-mi:“MI:0915”(physical association)	0.000
TMEM50A	LEPROT	psi-mi:“MI:0915”(physical association)	0.000
TMEM50A	LEPROTL1	psi-mi:“MI:0915”(physical association)	0.000
TMEM50A	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000
TMEM50A	AQP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): TMEM50A (Affinity Capture-RNA), TMEM50A (Affinity Capture-MS), TMEM50A (Positive Genetic), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), TMEM50A (Two-hybrid), LEPROT (Two-hybrid), HLA-DPA1 (Two-hybrid)

ESM2 similar proteins: A1CKG4, A1D708, A2XSY1, A4R2N5, A6QRX6, A6RRF7, A7EMV1, B0XXU1, B2AR67, O46521, O95214, O95807, P13498, P52650, Q0CNZ5, Q0JDK9, Q0V0G4, Q17QF8, Q1E1E0, Q28F21, Q2GSS4, Q32PD8, Q39080, Q3ZBX1, Q4WXT2, Q566G2, Q5PQQ4, Q5R5Z8, Q5RDE9, Q61462, Q62737, Q6CC06, Q6GM42, Q6GPA8, Q6P0C7, Q6PDU4, Q7S693, Q8K3C0, Q8TAC9, Q92535

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1008 predictions. Top by Δscore:

Variant	Effect	Δscore
1:25340471:A:AG	acceptor_gain	1.0000
1:25340471:AAGT:A	acceptor_gain	1.0000
1:25340472:A:AG	acceptor_gain	1.0000
1:25340473:G:GG	acceptor_gain	1.0000
1:25340473:GT:G	acceptor_gain	1.0000
1:25340574:GTACT:G	donor_gain	1.0000
1:25340579:AG:A	donor_loss	1.0000
1:25340580:G:A	donor_loss	1.0000
1:25340580:G:GG	donor_gain	1.0000
1:25340581:TA:T	donor_loss	1.0000
1:25340582:A:AG	donor_loss	1.0000
1:25340583:A:AC	donor_loss	1.0000
1:25343072:AT:A	donor_gain	1.0000
1:25343074:G:GG	donor_gain	1.0000
1:25338453:GGAC:G	donor_gain	0.9900
1:25338454:GACG:G	donor_gain	0.9900
1:25338457:G:GG	donor_gain	0.9900
1:25338772:A:T	donor_gain	0.9900
1:25340464:T:A	acceptor_loss	0.9900
1:25340471:AAG:A	acceptor_loss	0.9900
1:25340472:AGT:A	acceptor_gain	0.9900
1:25340473:G:GA	acceptor_loss	0.9900
1:25340473:GTG:G	acceptor_gain	0.9900
1:25340473:GTGA:G	acceptor_gain	0.9900
1:25340473:GTGAC:G	acceptor_gain	0.9900
1:25340576:ACTA:A	donor_gain	0.9900
1:25340577:CTA:C	donor_gain	0.9900
1:25340578:TA:T	donor_gain	0.9900
1:25342959:A:AG	acceptor_gain	0.9900
1:25342960:G:GT	acceptor_gain	0.9900

AlphaMissense

1031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:25340557:C:A	A24D	1.000
1:25340571:G:C	G29R	1.000
1:25340572:G:A	G29D	1.000
1:25342970:G:C	G35R	1.000
1:25342971:G:A	G35D	1.000
1:25342973:T:A	W36R	1.000
1:25342973:T:C	W36R	1.000
1:25342976:T:A	W37R	1.000
1:25342976:T:C	W37R	1.000
1:25343045:G:C	G60R	1.000
1:25343046:G:A	G60D	1.000
1:25351632:T:A	N71K	1.000
1:25351632:T:G	N71K	1.000
1:25351633:G:C	A72P	1.000
1:25352893:T:A	W96R	1.000
1:25352893:T:C	W96R	1.000
1:25352897:T:C	L97P	1.000
1:25352905:G:C	G100R	1.000
1:25352906:G:A	G100D	1.000
1:25352924:G:A	G106E	1.000
1:25360679:G:C	G150R	1.000
1:25360680:G:A	G150D	1.000
1:25340549:T:A	N21K	0.999
1:25340549:T:G	N21K	0.999
1:25340568:G:C	A28P	0.999
1:25340569:C:A	A28D	0.999
1:25342970:G:T	G35C	0.999
1:25342971:G:T	G35V	0.999
1:25342986:T:A	I40K	0.999
1:25342994:G:C	A43P	0.999

dbSNP variants (sampled 300 via entrez): RS1000082818 (1:25343450 A>G), RS1000357511 (1:25338456 C>G), RS1000392276 (1:25338618 C>G,T), RS1000414200 (1:25344860 T>C), RS1000479135 (1:25343144 A>G), RS1000561211 (1:25350010 C>A,T), RS1000825560 (1:25350174 A>G), RS1001036729 (1:25349663 C>G), RS1001086450 (1:25337327 C>T), RS1001099223 (1:25356532 T>C), RS1001432756 (1:25354949 T>A), RS1001529568 (1:25354529 C>T), RS1001536219 (1:25347247 T>C), RS1001550018 (1:25357578 T>A,C,G), RS1001588667 (1:25347715 T>A,C)

Disease associations

OMIM: gene MIM:605348 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001120_3	Erythrocyte sedimentation rate	2.000000e-13
GCST90002391_55	Mean corpuscular hemoglobin concentration	7.000000e-23
GCST90002391_56	Mean corpuscular hemoglobin concentration	1.000000e-24
GCST90002396_118	Mean reticulocyte volume	8.000000e-20
GCST90002397_617	Mean spheric corpuscular volume	5.000000e-42
GCST90002405_597	Reticulocyte count	7.000000e-37
GCST90002406_135	Reticulocyte fraction of red cells	3.000000e-37

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects methylation	2
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
methylparaben	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Colforsin	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Metribolone	increases expression	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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