TMEM185A

Summary

TMEM185A (transmembrane protein 185A, HGNC:17125) is a protein-coding gene on chromosome Xq28, encoding Transmembrane protein 185A (Q8NFB2).

The protein encoded by this gene is predicted to be a transmembrane protein. This gene is best known for localizing to the CpG island of the fragile site FRAXF. The 5’ untranslated region of this gene contains a CGG trinucleotide repeat sequence that normally consists of 7-40 tandem CGG repeats but which can expand to greater than 300 repeats. Methylation of the CpG island leads to transcriptional silencing of this gene, but neither the silencing nor an expanded repeat region appear to manifest itself in a clear phenotypic manner. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome.

Source: NCBI Gene 84548 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 80 total — 1 pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_032508

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17125
Approved symbol	TMEM185A
Name	transmembrane protein 185A
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000269556
Ensembl biotype	protein_coding
OMIM	300031
Entrez	84548

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000502618, ENST00000502858, ENST00000502900, ENST00000507237, ENST00000511776, ENST00000517359, ENST00000600449, ENST00000611119, ENST00000612022, ENST00000616857

RefSeq mRNA: 3 — MANE Select: NM_032508 NM_001174092, NM_001282302, NM_032508

CCDS: CCDS14689, CCDS55523, CCDS76041

Canonical transcript exons

ENST00000600449 — 7 exons

Exon	Start	End
ENSE00002983579	149600303	149600479
ENSE00003056222	149603987	149604070
ENSE00003196994	149599554	149599677
ENSE00003715964	149611287	149611463
ENSE00003726649	149608627	149608834
ENSE00003754583	149596556	149598255
ENSE00003845997	149631543	149631792

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 92.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6750 / max 41.7629, expressed in 1682 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200820	3.6058	1420
200821	2.0691	1344

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	92.65	gold quality
cardiac atrium	UBERON:0002081	91.89	gold quality
left ovary	UBERON:0002119	91.04	gold quality
cortical plate	UBERON:0005343	90.42	gold quality
right ovary	UBERON:0002118	90.32	gold quality
stromal cell of endometrium	CL:0002255	89.90	gold quality
apex of heart	UBERON:0002098	89.86	gold quality
skin of leg	UBERON:0001511	89.59	gold quality
heart left ventricle	UBERON:0002084	89.54	gold quality
calcaneal tendon	UBERON:0003701	89.39	gold quality
lower esophagus mucosa	UBERON:0035834	89.18	gold quality
colonic epithelium	UBERON:0000397	88.90	gold quality
cardiac ventricle	UBERON:0002082	88.79	gold quality
skin of abdomen	UBERON:0001416	88.61	gold quality
heart	UBERON:0000948	88.55	gold quality
mucosa of stomach	UBERON:0001199	88.30	gold quality
smooth muscle tissue	UBERON:0001135	88.04	gold quality
popliteal artery	UBERON:0002250	87.88	gold quality
tibial artery	UBERON:0007610	87.88	gold quality
zone of skin	UBERON:0000014	87.37	gold quality
right coronary artery	UBERON:0001625	87.37	gold quality
ventricular zone	UBERON:0003053	87.34	gold quality
ganglionic eminence	UBERON:0004023	87.34	gold quality
left adrenal gland cortex	UBERON:0035825	87.28	gold quality
secondary oocyte	CL:0000655	87.18	gold quality
esophagus mucosa	UBERON:0002469	87.18	gold quality
ectocervix	UBERON:0012249	87.17	gold quality
left adrenal gland	UBERON:0001234	87.13	gold quality
aorta	UBERON:0000947	87.12	gold quality
monocyte	CL:0000576	86.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.61
E-MTAB-2983	no	1.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting TMEM185A, 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-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-3664-5P	96.74	66.56	770
HSA-MIR-25-5P	87.02	64.95	84

Literature-anchored findings (GeneRIF, showing 2)

• Transcriptionally silenced in a normal individual with a FRAXF CGG full mutation (fragile site). (PMID:12404111)
• The mouse ee3 is an orphan G-protein-coupled receptor with potential connections to erythropoietin and 5HT2a receptor signalling. ee3_2, a similar gene, is also described, along with human orthologs. (PMID:15525354)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem185	ENSDARG00000044327
mus_musculus	Tmem185a	ENSMUSG00000073139
rattus_norvegicus	Tmem185a	ENSRNOG00000011047

Paralogs (2): TMEM60 (ENSG00000135211), TMEM185B (ENSG00000226479)

Protein

Protein identifiers

Transmembrane protein 185A — Q8NFB2 (reviewed: Q8NFB2)

Alternative names: Protein FAM11A

All UniProt accessions (8): Q8NFB2, A0A087X081, B7Z4G6, E5RFI9, E5RGV1, E7EMM1, H0YAP3, H0YBJ6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with MAP1B.

Subcellular location. Cell projection. Dendrite. Membrane.

Similarity. Belongs to the TMEM185 family.

RefSeq proteins (3): NP_001167563, NP_001269231, NP_115897* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF10269

UniProt features (11 total): transmembrane region 7, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFB2-F1	77.97	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, BENPORATH_ES_WITH_H3K27ME3, CHX10_01, TSENG_IRS1_TARGETS_DN, NKX22_01, GOCC_NEURON_PROJECTION, BRACHAT_RESPONSE_TO_CISPLATIN, RGAGGAARY_PU1_Q6, BRACHAT_RESPONSE_TO_METHOTREXATE_UP, BRACHAT_RESPONSE_TO_CAMPTOTHECIN_UP, FOX_Q2, TAATTA_CHX10_01

GO Biological Process (0):

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

GO Cellular Component (3): membrane (GO:0016020), dendrite (GO:0030425), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM185A	AFF2	P51816	950
TMEM185A	FMR1	Q06787	896
TMEM185A	FRA10AC1	Q70Z53	658
TMEM185A	CBL	P22681	604
TMEM185A	BGN	P13247	548
TMEM185A	HSFX4	A0A1B0GTS1	543
TMEM185A	AFF1	P51825	528
TMEM185A	AFF3	P51826	519
TMEM185A	EOLA1	Q8TE69	480
TMEM185A	GPR137C	Q8N3F9	467
TMEM185A	EOLA2	Q96DE9	446
TMEM185A	CXorf51A	A0A1B0GTR3	445
TMEM185A	DSG4	Q86SJ6	432
TMEM185A	GPR157	Q5UAW9	411
TMEM185A	MAGEA9B	P43362	398
TMEM185A	HSFX1	Q9UBD0	398

IntAct

32 interactions, top by confidence:

A	B	Type	Score
AGT	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
FOS	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
GATM	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
GRB2	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
HSF1	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
KLKB1	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
TMEM185A	LPL	psi-mi:“MI:0915”(physical association)	0.560
NDUFB10	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
VHL	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
TMEM185A	RER1	psi-mi:“MI:0914”(association)	0.350

BioGRID (155): CACNA2D1 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), PALM (Affinity Capture-MS), SMPDL3B (Affinity Capture-MS), NCAM1 (Affinity Capture-MS), CD109 (Affinity Capture-MS), PTPRG (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), CXADR (Affinity Capture-MS), TMEM185B (Affinity Capture-MS), RAP2A (Affinity Capture-MS), GAP43 (Affinity Capture-MS), DAAM1 (Affinity Capture-MS), CPNE8 (Affinity Capture-MS)

ESM2 similar proteins: A2AF53, A4FV75, A4K2N5, A4K2W1, A5A6S6, A6QL84, A6ZIQ8, A9JRA0, B1AZA5, D3ZEH5, D3ZXD8, E1BD52, O60337, P58749, Q08DE2, Q108U3, Q2TBU2, Q3SYY9, Q3TMP8, Q4R5E3, Q58DA4, Q5BJW3, Q5JZQ8, Q5R8H8, Q5R9W1, Q5RBJ7, Q5RFE0, Q5ZII3, Q62302, Q6UWH6, Q6ZQ89, Q78S06, Q7SYC7, Q7ZUA6, Q86W33, Q8CIF6, Q8K0B2, Q8N2H4, Q8NBJ9, Q8NFB2

Diamond homologs: A2AF53, Q08DE2, Q5R8H8, Q7SYC7, Q8NFB2, Q8R3R5, Q9H7F4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685716	GRCh37/hg19 Xq27.1-28(chrX:139513270-149234353)x2	Pathogenic

SpliceAI

1462 predictions. Top by Δscore:

Variant	Effect	Δscore
X:149598251:CCACC:C	acceptor_gain	1.0000
X:149598252:CACC:C	acceptor_gain	1.0000
X:149598252:CACCC:C	acceptor_gain	1.0000
X:149598253:ACC:A	acceptor_gain	1.0000
X:149598254:CC:C	acceptor_gain	1.0000
X:149598254:CCC:C	acceptor_gain	1.0000
X:149598255:CC:C	acceptor_gain	1.0000
X:149598256:C:CC	acceptor_gain	1.0000
X:149598256:C:T	acceptor_gain	1.0000
X:149599552:A:AC	donor_gain	1.0000
X:149599553:C:CC	donor_gain	1.0000
X:149599553:CA:C	donor_gain	1.0000
X:149599553:CAGTG:C	donor_gain	1.0000
X:149599565:C:A	donor_gain	1.0000
X:149599674:GAAT:G	acceptor_gain	1.0000
X:149599677:TC:T	acceptor_loss	1.0000
X:149599678:C:CA	acceptor_loss	1.0000
X:149599678:C:CC	acceptor_gain	1.0000
X:149600297:GCTTA:G	donor_loss	1.0000
X:149600298:CTTA:C	donor_loss	1.0000
X:149600299:TTA:T	donor_loss	1.0000
X:149600300:TACCT:T	donor_loss	1.0000
X:149600301:ACCTC:A	donor_loss	1.0000
X:149600302:C:G	donor_loss	1.0000
X:149600302:CCT:C	donor_gain	1.0000
X:149600435:C:CT	acceptor_gain	1.0000
X:149600476:CAAC:C	acceptor_gain	1.0000
X:149603985:A:AC	donor_gain	1.0000
X:149603985:ACAAG:A	donor_gain	1.0000
X:149603986:C:CC	donor_gain	1.0000

AlphaMissense

2293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:149608656:A:G	W132R	1.000
X:149608656:A:T	W132R	1.000
X:149598246:C:T	G273D	0.999
X:149600461:A:G	W176R	0.999
X:149600461:A:T	W176R	0.999
X:149600466:G:C	P174R	0.999
X:149600466:G:T	P174Q	0.999
X:149603998:A:G	W166R	0.999
X:149603998:A:T	W166R	0.999
X:149604033:A:T	I154K	0.999
X:149604042:A:T	L151H	0.999
X:149604047:G:C	N149K	0.999
X:149604047:G:T	N149K	0.999
X:149608654:C:A	W132C	0.999
X:149608654:C:G	W132C	0.999
X:149608658:A:T	V131D	0.999
X:149608697:G:C	P118R	0.999
X:149608697:G:T	P118Q	0.999
X:149611321:C:G	G61R	0.999
X:149611321:C:T	G61R	0.999
X:149611360:A:G	W48R	0.999
X:149611360:A:T	W48R	0.999
X:149598246:C:A	G273V	0.998
X:149598247:C:G	G273R	0.998
X:149598253:A:G	W271R	0.998
X:149598253:A:T	W271R	0.998
X:149599554:A:G	W270R	0.998
X:149599554:A:T	W270R	0.998
X:149600313:A:G	L225P	0.998
X:149600319:G:C	P223R	0.998

dbSNP variants (sampled 300 via entrez): RS1000355788 (X:149606477 G>A), RS1000742527 (X:149605297 C>T), RS1000807161 (X:149606854 C>T), RS1001005785 (X:149622943 T>C), RS1001093119 (X:149605001 G>A), RS1001447363 (X:149632498 T>C), RS1002244244 (X:149605716 C>T), RS1002329853 (X:149614340 A>G), RS1002598351 (X:149605378 T>C), RS1002856140 (X:149609082 G>A,C), RS1002908543 (X:149609524 C>T), RS1003193327 (X:149606956 G>C), RS1003242364 (X:149607479 G>A), RS1003377817 (X:149616712 T>C), RS1003511569 (X:149626106 G>A)

Disease associations

OMIM: gene MIM:300031 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000118	Phenotypic abnormality
HP:0003564	Folate-dependent fragile site at Xq28
HP:0012758	Neurodevelopmental delay

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	increases expression, affects cotreatment	1
beta-lapachone	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
Antimycin A	decreases expression	1
Arsenic	affects expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Triclosan	decreases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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