TMEM174

Summary

TMEM174 (transmembrane protein 174, HGNC:28187) is a protein-coding gene on chromosome 5q13.2, encoding Transmembrane protein 174 (Q8WUU8). Regulator of plasma phosphate homeostasis.

Predicted to be involved in phosphate ion homeostasis. Located in endoplasmic reticulum membrane.

Source: NCBI Gene 134288 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_153217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28187
Approved symbol	TMEM174
Name	transmembrane protein 174
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC13034, FLJ31268
Ensembl gene	ENSG00000164325
Ensembl biotype	protein_coding
OMIM	614909
Entrez	134288

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296776, ENST00000511737

RefSeq mRNA: 1 — MANE Select: NM_153217 NM_153217

CCDS: CCDS4018

Canonical transcript exons

ENST00000296776 — 2 exons

Exon	Start	End
ENSE00001733771	73173193	73173869
ENSE00002243072	73174060	73175143

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 99.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0776 / max 73.1771, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57034	0.0587	3
57035	0.0189	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.57	gold quality
left ventricle myocardium	UBERON:0006566	93.49	gold quality
adult mammalian kidney	UBERON:0000082	87.82	gold quality
kidney	UBERON:0002113	83.86	gold quality
tibialis anterior	UBERON:0001385	83.79	silver quality
renal medulla	UBERON:0000362	83.72	gold quality
adult organism	UBERON:0007023	83.55	gold quality
cardia of stomach	UBERON:0001162	79.85	silver quality
vena cava	UBERON:0004087	79.59	gold quality
pons	UBERON:0000988	79.44	silver quality
subthalamic nucleus	UBERON:0001906	79.38	silver quality
pericardium	UBERON:0002407	78.67	silver quality
saphenous vein	UBERON:0007318	78.41	silver quality
inferior vagus X ganglion	UBERON:0005363	78.22	silver quality
oocyte	CL:0000023	78.06	silver quality
lateral nuclear group of thalamus	UBERON:0002736	77.79	silver quality
dorsal root ganglion	UBERON:0000044	77.43	silver quality
trigeminal ganglion	UBERON:0001675	77.39	silver quality
superior vestibular nucleus	UBERON:0007227	77.23	silver quality
medulla oblongata	UBERON:0001896	77.20	silver quality
substantia nigra pars reticulata	UBERON:0001966	77.16	silver quality
nasal cavity epithelium	UBERON:0005384	77.13	gold quality
myocardium	UBERON:0002349	77.03	gold quality
substantia nigra pars compacta	UBERON:0001965	76.87	silver quality
cerebellar vermis	UBERON:0004720	76.73	gold quality
synovial joint	UBERON:0002217	75.65	silver quality
ileal mucosa	UBERON:0000331	75.54	silver quality
upper arm skin	UBERON:0004263	75.19	gold quality
penis	UBERON:0000989	75.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting TMEM174, 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-6740-5P	100.00	65.64	932
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-647	97.73	67.79	927
HSA-MIR-558	97.50	67.16	977
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-3184-3P	96.96	66.91	845
HSA-MIR-3200-3P	95.41	64.23	396

Literature-anchored findings (GeneRIF, showing 1)

• these results suggest the potential role of TMEM174 in renal development and physiological function. (PMID:20331980)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem174	ENSDARG00000035388
mus_musculus	Tmem174	ENSMUSG00000046082
rattus_norvegicus	Tmem174	ENSRNOG00000015472

Protein

Protein identifiers

Transmembrane protein 174 — Q8WUU8 (reviewed: Q8WUU8)

All UniProt accessions (1): Q8WUU8

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of plasma phosphate homeostasis. Decreases serum inorganic phosphate (Pi) uptake by regulating the sodium-phosphate cotransporter SLC34A1 trafficking by PTH and FGF23 in the kidney.

Subunit / interactions. Interacts with SLC34A1; regulates SLC34A1 internalization by PTH and FGF23.

Subcellular location. Endoplasmic reticulum membrane. Apical cell membrane.

Tissue specificity. Predominantly expressed in kidney. Selectively localized in the apical membrane of renal proximal tubule epithelial cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WUU8-1	1	yes
Q8WUU8-2	2

RefSeq proteins (1): NP_694949* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027835	TMEM174	Family

Pfam: PF15029

UniProt features (4 total): transmembrane region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUU8-F1	58.68	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): GOCC_APICAL_PLASMA_MEMBRANE, GOCC_APICAL_PART_OF_CELL, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_PLASMA_MEMBRANE_REGION, GOCC_ORGANELLE_SUBCOMPARTMENT, MIKKELSEN_IPS_WITH_HCP_H3K27ME3, MIKKELSEN_ES_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, NFE2L2.V2, MIR32_3P, MIR3185, GSE10463_CD40L_AND_VA347_VS_CD40L_IN_DC_DN

GO Biological Process (1): phosphate ion homeostasis (GO:0055062)

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

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), apical plasma membrane (GO:0016324), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inorganic ion homeostasis	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
apical part of cell	1
plasma membrane region	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM174	INSYN2B	A6NMK8	591
TMEM174	LRRC31	Q6UY01	557
TMEM174	SZRD1	Q7Z422	541
TMEM174	MEP1A	Q16819	503
TMEM174	FCHO2	Q0JRZ9	490
TMEM174	TM9SF1	O15321	479
TMEM174	TMEM161A	Q9NX61	471
TMEM174	TMEM171	Q8WVE6	465
TMEM174	LYPD6	Q86Y78	457
TMEM174	GARIN1B	Q96KD3	450
TMEM174	TMEM207	Q6UWW9	448
TMEM174	LRRIQ4	A6NIV6	435
TMEM174	ZNF366	Q8N895	430
TMEM174	LRRC34	Q8IZ02	427
TMEM174	NSA2	O95478	421
TMEM174	KRTAP8-1	Q8IUC2	421

IntAct

42 interactions, top by confidence:

A	B	Type	Score
SGTA	TMEM174	psi-mi:“MI:0915”(physical association)	0.720
TMEM174	SGTA	psi-mi:“MI:0915”(physical association)	0.720
TMEM174	CMTM7	psi-mi:“MI:0915”(physical association)	0.600
CACNB2	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
KRT31	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
KRT34	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
TMEM174	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
TMEM174	PLLP	psi-mi:“MI:0915”(physical association)	0.560
MAL	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
BAG3	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
EMD	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
KLF11	TMEM174	psi-mi:“MI:0915”(physical association)	0.560
TMEM174	TOM1L1	psi-mi:“MI:0914”(association)	0.350
TMEM174	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
TMEM174	KRT34	psi-mi:“MI:0915”(physical association)	0.000
TMEM174	KRT31	psi-mi:“MI:0915”(physical association)	0.000
SGTA	TMEM174	psi-mi:“MI:0915”(physical association)	0.000
CMTM7	TMEM174	psi-mi:“MI:0915”(physical association)	0.000
PLLP	TMEM174	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): TMEM174 (Two-hybrid), SGTA (Two-hybrid), TMEM174 (Two-hybrid), TMEM174 (Two-hybrid), TMEM174 (Two-hybrid), TMEM174 (Two-hybrid), TMEM174 (Two-hybrid), TMEM174 (Two-hybrid), TMEM174 (Two-hybrid), TMEM174 (Two-hybrid), CACNB2 (Two-hybrid), MAL (Two-hybrid), CYSRT1 (Two-hybrid), HECW2 (Affinity Capture-MS), WDR44 (Affinity Capture-MS)

ESM2 similar proteins: A2AR95, A4IHY6, B7ZWI3, D3ZF92, O15165, O43278, O75509, O88204, P98153, P98154, Q0VBF2, Q1L8G6, Q29RU0, Q4KMG9, Q566M8, Q5DTZ6, Q5HZW5, Q5R662, Q5R8E0, Q5RD34, Q5RF74, Q5VUB5, Q61003, Q68FU0, Q6AXS2, Q6NRX0, Q6UWW9, Q6ZPS6, Q6ZUJ8, Q7TQH7, Q86YD5, Q8BGN6, Q8BLD6, Q8BUJ9, Q8R182, Q8TEB7, Q8WUU8, Q91ZV2, Q91ZV3, Q96PD2

Diamond homologs: Q5R8E0, Q68FU0, Q8WUU8, Q9DCX7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

100 predictions. Top by Δscore:

Variant	Effect	Δscore
5:73173865:CACAG:C	donor_loss	0.9800
5:73173867:CAGG:C	donor_loss	0.9800
5:73173870:GTAT:G	donor_loss	0.9800
5:73173871:T:G	donor_loss	0.9800
5:73174059:GGCCC:G	acceptor_gain	0.9700
5:73174054:TTTCA:T	acceptor_loss	0.9600
5:73174055:TTCAG:T	acceptor_loss	0.9600
5:73174056:TCAGG:T	acceptor_loss	0.9600
5:73174057:CAG:C	acceptor_loss	0.9600
5:73174058:A:AG	acceptor_gain	0.9600
5:73174058:A:C	acceptor_loss	0.9600
5:73174059:G:GA	acceptor_loss	0.9600
5:73174059:G:GG	acceptor_gain	0.9600
5:73174052:C:G	acceptor_gain	0.8900
5:73174058:AG:A	acceptor_gain	0.8800
5:73174059:GG:G	acceptor_gain	0.8800
5:73174053:A:AG	acceptor_gain	0.8700
5:73174059:GGCC:G	acceptor_gain	0.8600
5:73174106:G:GT	donor_gain	0.8500
5:73173809:A:G	donor_gain	0.8100
5:73174051:A:AG	acceptor_gain	0.8100
5:73174059:GGC:G	acceptor_gain	0.8100
5:73174054:T:G	acceptor_gain	0.8000
5:73173654:GC:G	donor_gain	0.7900
5:73174891:TGCA:T	acceptor_gain	0.7600
5:73174100:G:GT	donor_gain	0.7000
5:73174139:G:GT	donor_gain	0.7000
5:73174893:CA:C	acceptor_gain	0.6700
5:73174894:AA:A	acceptor_gain	0.6700
5:73173853:G:GT	donor_gain	0.6400

AlphaMissense

1580 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:73173394:G:A	G51R	0.998
5:73173394:G:C	G51R	0.998
5:73173373:G:C	G44R	0.996
5:73173395:G:A	G51E	0.996
5:73173496:T:C	F85L	0.996
5:73173498:C:A	F85L	0.996
5:73173498:C:G	F85L	0.996
5:73173374:G:A	G44D	0.995
5:73173394:G:T	G51W	0.995
5:73173466:G:A	G75R	0.995
5:73173466:G:C	G75R	0.995
5:73173487:G:A	G82R	0.994
5:73173487:G:C	G82R	0.994
5:73173473:T:A	V77D	0.993
5:73173415:G:C	G58R	0.992
5:73173634:T:C	F131L	0.992
5:73173636:C:A	F131L	0.992
5:73173636:C:G	F131L	0.992
5:73173362:T:C	L40S	0.991
5:73173385:G:A	G48R	0.991
5:73173385:G:C	G48R	0.991
5:73173476:T:C	L78P	0.991
5:73173476:T:G	L78R	0.991
5:73173488:G:A	G82E	0.991
5:73173395:G:T	G51V	0.989
5:73173476:T:A	L78Q	0.989
5:73173383:T:A	L47Q	0.988
5:73173494:C:A	T84K	0.988
5:73173607:T:C	F122L	0.988
5:73173609:C:A	F122L	0.988

dbSNP variants (sampled 300 via entrez): RS1001733631 (5:73174746 G>A), RS1002056662 (5:73174698 G>A), RS1002213965 (5:73174473 C>T), RS1002781971 (5:73172619 G>A), RS1006422811 (5:73172465 G>A), RS1006756004 (5:73175350 G>A), RS1007417131 (5:73172896 C>T), RS1007584723 (5:73172731 C>T), RS1008686431 (5:73171555 C>G), RS1008887110 (5:73175429 C>A), RS1009008561 (5:73173968 C>A,T), RS1010406332 (5:73174623 G>T), RS1010777340 (5:73171612 A>T), RS1011433788 (5:73175527 T>G), RS1011994557 (5:73172210 A>G)

Disease associations

OMIM: gene MIM:614909 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001610_12	Renal function-related traits (BUN)	2.000000e-06
GCST003476_8	Eyebrow thickness	3.000000e-07
GCST003477_7	Monobrow thickness	4.000000e-07
GCST003996_7	Monobrow	7.000000e-35
GCST005986_7	Blood urea nitrogen levels	1.000000e-11
GCST012146_10	Hemoglobin levels	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
propionaldehyde	decreases expression	1
2-palmitoylglycerol	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Drugs, Chinese Herbal	increases expression	1
Naphthoquinones	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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