TMEM221

Summary

TMEM221 (transmembrane protein 221, HGNC:21943) is a protein-coding gene on chromosome 19p13.11, encoding Transmembrane protein 221 (A6NGB7).

Predicted to be located in membrane.

Source: NCBI Gene 100130519 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001190844

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21943
Approved symbol	TMEM221
Name	transmembrane protein 221
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	Jiraiya
Ensembl gene	ENSG00000188051
Ensembl biotype	protein_coding
Entrez	100130519

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000341130, ENST00000593461

RefSeq mRNA: 1 — MANE Select: NM_001190844 NM_001190844

CCDS: CCDS54230

Canonical transcript exons

ENST00000341130 — 3 exons

Exon	Start	End
ENSE00001375301	17448143	17448668
ENSE00001383866	17435509	17436927
ENSE00003504005	17445199	17445284

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 82.78.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4821 / max 26.0160, expressed in 258 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179868	0.4821	258

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	82.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.34	gold quality
left ovary	UBERON:0002119	74.11	gold quality
right adrenal gland cortex	UBERON:0035827	73.78	gold quality
right ovary	UBERON:0002118	73.41	gold quality
right adrenal gland	UBERON:0001233	72.77	gold quality
prefrontal cortex	UBERON:0000451	72.46	gold quality
left adrenal gland	UBERON:0001234	71.78	gold quality
left adrenal gland cortex	UBERON:0035825	71.62	gold quality
right frontal lobe	UBERON:0002810	71.56	gold quality
anterior cingulate cortex	UBERON:0009835	71.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.94	gold quality
adrenal cortex	UBERON:0001235	69.86	gold quality
ganglionic eminence	UBERON:0004023	69.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.32	gold quality
ovary	UBERON:0000992	67.93	gold quality
adrenal gland	UBERON:0002369	67.51	gold quality
amygdala	UBERON:0001876	66.81	gold quality
neocortex	UBERON:0001950	66.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.36	gold quality
frontal cortex	UBERON:0001870	66.28	gold quality
buccal mucosa cell	CL:0002336	66.20	gold quality
stromal cell of endometrium	CL:0002255	64.91	gold quality
cerebral cortex	UBERON:0000956	62.46	gold quality
left uterine tube	UBERON:0001303	62.40	gold quality
right uterine tube	UBERON:0001302	62.35	gold quality
adenohypophysis	UBERON:0002196	59.61	gold quality
forebrain	UBERON:0001890	59.53	gold quality
brain	UBERON:0000955	58.40	gold quality
hypothalamus	UBERON:0001898	58.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting TMEM221, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-670-3P	99.03	68.88	2404

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem221	ENSMUSG00000043664
rattus_norvegicus	Tmem221	ENSRNOG00000018167

Protein

Protein identifiers

Transmembrane protein 221 — A6NGB7 (reviewed: A6NGB7)

All UniProt accessions (1): A6NGB7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001177773* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029201	Jiraiya	Family
IPR053101	TM221	Family

Pfam: PF15038

UniProt features (6 total): transmembrane region 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NGB7-F1	68.14	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): chr19p13, CHAF1B_TARGET_GENES, SUPT16H_TARGET_GENES, MIR6504_3P, MIR10399_5P, MIR670_3P, MIR5004_5P, MIR6072, MIR1224_5P, MIR4712_3P, MIR6891_3P, MIR4654, MIR1225_3P, MIR4769_5P, MANNO_MIDBRAIN_NEUROTYPES_HRGL2A

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

219 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM221	GPR137C	Q8N3F9	630
TMEM221	TMEM132E	Q6IEE7	590
TMEM221	TMEM171	Q8WVE6	572
TMEM221	LHFPL7	Q6ICI0	552
TMEM221	OVOL3	O00110	519
TMEM221	GPR162	Q16538	509
TMEM221	TMEM38A	Q9H6F2	487
TMEM221	TMEM150C	B9EJG8	484
TMEM221	TMC5	Q6UXY8	472
TMEM221	TMEM212	A6NML5	470
TMEM221	OPRD1	P41143	391
TMEM221	ADGRB2	O60241	390
TMEM221	GPR37	O15354	381
TMEM221	WDFY1	Q8IWB7	378
TMEM221	TMEM45A	Q9NWC5	357

IntAct

2 interactions, top by confidence:

A	B	Type	Score
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): TMEM221 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A2R8YCJ5, A2A699, A2AEV7, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NL88, A8MVW0, A9JSM3, B2RU40, B8ZZ34, C9JH25, D4A9R4, J3QNX5, P0CG09, P98077, Q0VD38, Q14761, Q17QH7, Q29RK8, Q2KJ18, Q2M3V2, Q3SX20, Q5BJT1, Q5HZJ5, Q5RKR3, Q5T442, Q64697, Q69YZ2, Q6PB97, Q6PCT2, Q6UXK2, Q6ZMQ8, Q6ZVH7, Q6ZW31, Q80XF7, Q8BLS7

Diamond homologs: A6NGB7, Q8K071

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

707 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17436923:CAGTG:C	acceptor_gain	1.0000
19:17448144:T:TA	donor_gain	1.0000
19:17436928:C:CC	acceptor_gain	0.9900
19:17445282:GACCT:G	acceptor_loss	0.9900
19:17445283:ACCT:A	acceptor_loss	0.9900
19:17445284:CCTGG:C	acceptor_loss	0.9900
19:17445285:CT:C	acceptor_loss	0.9900
19:17445285:CTGGA:C	acceptor_loss	0.9900
19:17445286:T:C	acceptor_loss	0.9900
19:17447841:C:A	donor_gain	0.9900
19:17448141:ACCT:A	donor_gain	0.9900
19:17448142:CCTC:C	donor_gain	0.9900
19:17436735:T:TA	donor_gain	0.9800
19:17436924:AGTG:A	acceptor_gain	0.9800
19:17436925:GTG:G	acceptor_gain	0.9800
19:17436926:TG:T	acceptor_gain	0.9800
19:17436927:GC:G	acceptor_loss	0.9800
19:17436929:T:G	acceptor_loss	0.9800
19:17445290:A:AC	acceptor_gain	0.9800
19:17447835:AG:A	donor_gain	0.9800
19:17448138:CCTA:C	donor_loss	0.9800
19:17448141:A:T	donor_loss	0.9800
19:17448142:C:CT	donor_loss	0.9800
19:17436488:C:CA	donor_gain	0.9700
19:17436898:C:CT	acceptor_gain	0.9700
19:17445194:CACA:C	donor_loss	0.9700
19:17445195:ACAC:A	donor_loss	0.9700
19:17445196:CA:C	donor_loss	0.9700
19:17445198:C:CA	donor_loss	0.9700
19:17445198:C:G	donor_loss	0.9700

AlphaMissense

1806 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17436899:G:C	F145L	0.972
19:17436899:G:T	F145L	0.972
19:17436901:A:G	F145L	0.972
19:17448384:C:G	G27R	0.956
19:17445226:A:G	C127R	0.952
19:17448414:C:G	G17R	0.952
19:17436856:C:G	G160R	0.946
19:17445272:A:C	F111L	0.943
19:17445272:A:T	F111L	0.943
19:17445274:A:G	F111L	0.943
19:17436855:C:T	G160D	0.935
19:17436873:G:T	A154D	0.932
19:17436901:A:T	F145I	0.932
19:17448367:A:C	F32L	0.928
19:17448367:A:T	F32L	0.928
19:17448369:A:G	F32L	0.928
19:17445220:C:G	G129R	0.927
19:17445220:C:T	G129R	0.927
19:17448401:G:T	A21D	0.925
19:17436862:C:G	G158R	0.916
19:17448210:A:G	C85R	0.916
19:17445223:A:G	C128R	0.912
19:17436900:A:C	F145C	0.905
19:17445219:C:T	G129E	0.905
19:17445235:C:G	G124R	0.902
19:17448413:C:T	G17D	0.899
19:17436885:C:T	G150D	0.897
19:17448219:C:G	G82R	0.896
19:17448219:C:T	G82R	0.896
19:17448374:A:G	L30P	0.895

dbSNP variants (sampled 300 via entrez): RS1000017887 (19:17449619 G>A), RS1000226568 (19:17445724 A>C,G), RS1000280481 (19:17439988 A>G), RS1000348743 (19:17440156 C>A), RS1000353612 (19:17440946 G>A), RS1000356501 (19:17438072 A>C), RS1000384639 (19:17441271 C>G), RS1000622515 (19:17439807 G>A), RS1000717311 (19:17440066 G>A), RS1000898068 (19:17447046 A>C), RS1000964632 (19:17444407 C>T), RS1001314005 (19:17445796 A>G), RS1001504520 (19:17440593 T>C), RS1001601400 (19:17446193 CATCCATCCATCT>C), RS1001805334 (19:17440438 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006088_10	Familial squamous cell lung carcinoma	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006953	family history of lung cancer

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fluorene-9-bisphenol	decreases expression	1
titanium dioxide	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	decreases methylation	1
Phenylmercuric Acetate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1

Clinical trials (associated diseases)

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