MIPOL1

Summary

MIPOL1 (mirror-image polydactyly 1, HGNC:21460) is a protein-coding gene on chromosome 14q13.3-q21.1, encoding Mirror-image polydactyly gene 1 protein (Q8TD10).

This gene encodes a coiled-coil domain-containing protein. The encoded protein may function as a tumor suppressor. A translocation that results in truncation of the protein encoded by this locus has been associated with mirror-image polydactyly, also known as Laurin-Sandrow Syndrome. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 145282 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_001388067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21460
Approved symbol	MIPOL1
Name	mirror-image polydactyly 1
Location	14q13.3-q21.1
Locus type	gene with protein product
Status	Approved
Aliases	CCDC193
Ensembl gene	ENSG00000151338
Ensembl biotype	protein_coding
OMIM	606850
Entrez	145282

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 49 protein_coding, 9 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay, 1 TEC

ENST00000327441, ENST00000396294, ENST00000537471, ENST00000539062, ENST00000539174, ENST00000553349, ENST00000554114, ENST00000554829, ENST00000554930, ENST00000555870, ENST00000556451, ENST00000556615, ENST00000556753, ENST00000556940, ENST00000624539, ENST00000684589, ENST00000694961, ENST00000694962, ENST00000694963, ENST00000694964, ENST00000694965, ENST00000694966, ENST00000694967, ENST00000694968, ENST00000694969, ENST00000694970, ENST00000694971, ENST00000694972, ENST00000695406, ENST00000698512, ENST00000909321, ENST00000909322, ENST00000909323, ENST00000909324, ENST00000909325, ENST00000909326, ENST00000909327, ENST00000909328, ENST00000909329, ENST00000909330, ENST00000909331, ENST00000931726, ENST00000931727, ENST00000931728, ENST00000931729, ENST00000931730, ENST00000931731, ENST00000971096, ENST00000971097, ENST00000971098, ENST00000971099, ENST00000971100, ENST00000971101, ENST00000971102, ENST00000971103, ENST00000971104, ENST00000971105, ENST00000971106, ENST00000971107, ENST00000971108, ENST00000971109, ENST00000971110, ENST00000971111

RefSeq mRNA: 13 — MANE Select: NM_001388067 NM_001195296, NM_001195297, NM_001388067, NM_001388068, NM_001388069, NM_001388070, NM_001388071, NM_001388072, NM_001388073, NM_001388074, NM_001388075, NM_001388077, NM_138731

CCDS: CCDS91866, CCDS91869, CCDS9664

Canonical transcript exons

ENST00000684589 — 13 exons

Exon	Start	End
ENSE00001524534	37247103	37247240
ENSE00003522523	37268658	37268793
ENSE00003530918	37285318	37285447
ENSE00003557731	37308056	37308089
ENSE00003558192	37266938	37267169
ENSE00003593898	37308349	37308519
ENSE00003639893	37270420	37270525
ENSE00003655554	37247829	37247907
ENSE00003659980	37369517	37369624
ENSE00003674114	37422855	37422949
ENSE00003917032	37197937	37198104
ENSE00003917984	37546905	37551259
ENSE00003963252	37499908	37500138

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 94.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5410 / max 533.4573, expressed in 1425 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139306	3.6748	1240
139308	3.5707	1170
139307	0.6312	285
139305	0.3667	206
139304	0.2875	129
139318	0.0101	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.31	gold quality
sural nerve	UBERON:0015488	82.38	gold quality
colonic epithelium	UBERON:0000397	81.87	gold quality
adrenal tissue	UBERON:0018303	80.54	gold quality
left testis	UBERON:0004533	79.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.95	gold quality
tendon	UBERON:0000043	79.87	gold quality
testis	UBERON:0000473	79.76	gold quality
right testis	UBERON:0004534	79.45	gold quality
popliteal artery	UBERON:0002250	77.69	gold quality
tibial artery	UBERON:0007610	77.67	gold quality
ventricular zone	UBERON:0003053	77.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.10	gold quality
left ovary	UBERON:0002119	76.81	gold quality
ectocervix	UBERON:0012249	76.58	gold quality
islet of Langerhans	UBERON:0000006	76.57	gold quality
aorta	UBERON:0000947	76.41	gold quality
stromal cell of endometrium	CL:0002255	76.20	gold quality
body of pancreas	UBERON:0001150	76.02	gold quality
cortical plate	UBERON:0005343	75.93	gold quality
pancreas	UBERON:0001264	75.52	gold quality
smooth muscle tissue	UBERON:0001135	75.49	gold quality
ascending aorta	UBERON:0001496	75.34	gold quality
endocervix	UBERON:0000458	75.21	gold quality
thoracic aorta	UBERON:0001515	75.19	gold quality
body of uterus	UBERON:0009853	75.07	gold quality
right ovary	UBERON:0002118	74.86	gold quality
lower esophagus mucosa	UBERON:0035834	74.66	gold quality
ovary	UBERON:0000992	74.55	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	8146.92
E-GEOD-130473	yes	2442.31
E-GEOD-106540	yes	1423.96
E-CURD-97	yes	1079.18
E-MTAB-5061	yes	574.08
E-GEOD-81547	yes	455.17
E-MTAB-10137	yes	377.74
E-MTAB-7052	yes	338.46
E-ANND-3	yes	7.12
E-GEOD-150728	no	2985.24
E-MTAB-9067	no	1217.78
E-GEOD-98556	no	817.82
E-CURD-89	no	391.25
E-GEOD-76312	no	271.39
E-GEOD-70580	no	122.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

203 targeting MIPOL1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 4)

• candidate gene for mirror-image polydactyly of hands and feet anomaly. Maps to 14q13. (PMID:11954550)
• Study provides compelling evidence that chromosome 14 harbors tumor suppressor genes associated with NPC and that a candidate gene, MIPOL1, is associated with tumor development. (PMID:19667180)
• To date, at least ten loci and four non-syndromic polydactyly-causing genes, including the GLI3 gene, the ZNF141 gene, the MIPOL1 gene and the PITX1 gene, have been identified. (Review) (PMID:26515020)
• Functional characterization of a candidate tumor suppressor gene, Mirror Image Polydactyly 1, in nasopharyngeal carcinoma. (PMID:31609475)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mipol1	ENSDARG00000104845
mus_musculus	Mipol1	ENSMUSG00000047022
rattus_norvegicus	Mipol1	ENSRNOG00000009151

Protein

Protein identifiers

Mirror-image polydactyly gene 1 protein — Q8TD10 (reviewed: Q8TD10)

All UniProt accessions (15): A0A8Q3SHM7, A0A8Q3SHT3, A0A8Q3SHU0, A0A8Q3SHU5, A0A8Q3SHV0, A0A8Q3SHV2, A0A8Q3SHY7, A0A8Q3SI06, A0A8Z5CCZ9, Q8TD10, G3V2C4, G3V3K8, G3V5R6, G5EA54, Q49AL5

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed very weakly in heart, liver, skeletal muscle, kidney, pancreas and fetal kidney. Not detected in brain, placenta and lung.

Disease relevance. A chromosomal aberration involving MIPOL1 is found in a patient with mirror-image polydactyly of hands and feet without other anomalies (MIP). Translocation t(2;14)(p23.3;q13). MIP is a very rare congenital anomaly characterized by mirror-image duplication of digits. MIP is occasionally associated with dimelia of the ulna and fibula, tibial and/or fibular hypoplasia, nasal abnormality and other malformations. Most MIP cases are sporadic, but very rare parent-child transmissions observed in familial cases suggest an autosomal mode of inheritance.

Miscellaneous. May be due to a competing acceptor splice site.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TD10-1	1	yes
Q8TD10-2	2
Q8TD10-3	3

RefSeq proteins (13): NP_001182225, NP_001182226, NP_001374996, NP_001374997, NP_001374998, NP_001374999, NP_001375000, NP_001375001, NP_001375002, NP_001375003, NP_001375004, NP_001375006, NP_620059 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026175	MIPOL1	Family

UniProt features (9 total): splice variant 3, coiled-coil region 2, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD10-F1	77.51	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, ACATTCC_MIR1_MIR206, AACTTT_UNKNOWN, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, chr14q13, ACACTCC_MIR122A, MODULE_342, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GCNP_SHH_UP_EARLY.V1_DN, GSE14699_NAIVE_VS_DELETIONAL_TOLERANCE_CD8_TCELL_DN, CBX7_TARGET_GENES, COBLL1_TARGET_GENES, NFE2L1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIPOL1	SLC25A21	Q9BQT8	731
MIPOL1	PITX2	Q99697	657
MIPOL1	PITX1	P78337	651
MIPOL1	CARD14	Q9BXL6	548
MIPOL1	ETV1	P50549	525
MIPOL1	ZNF141	Q15928	515
MIPOL1	FOXC1	Q12948	494
MIPOL1	RUSC2	Q8N2Y8	483
MIPOL1	DLX2	Q07687	469
MIPOL1	SLC45A3	Q96JT2	456
MIPOL1	ALX3	O95076	455
MIPOL1	SMIM23	A6NLE4	448
MIPOL1	IGFBPL1	Q8WX77	442
MIPOL1	IQCE	Q6IPM2	431
MIPOL1	OTP	Q5XKR4	424

IntAct

305 interactions, top by confidence:

A	B	Type	Score
SSX3	MIPOL1	psi-mi:“MI:0915”(physical association)	0.780
MIPOL1	SSX3	psi-mi:“MI:0915”(physical association)	0.780
MIPOL1	PRPF31	psi-mi:“MI:0915”(physical association)	0.720
CCT3	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	UBE2K	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	BYSL	psi-mi:“MI:0915”(physical association)	0.720
FAM161A	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	ZGPAT	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	MAGEA6	psi-mi:“MI:0915”(physical association)	0.720
TTC12	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
SMARCE1	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
SCNM1	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
ENKD1	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
PRPF31	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	CCT3	psi-mi:“MI:0915”(physical association)	0.720
UBE2K	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
BYSL	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
MAGEA6	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	TTC12	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	SMARCE1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (128): MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid), MIPOL1 (Two-hybrid)

ESM2 similar proteins: A0JMQ7, A2AM05, A2AUM9, A6PWD2, A7MD70, B1AJZ9, O35550, O35551, O75330, O94986, P0CB05, Q03410, Q05D60, Q15276, Q15431, Q17QT2, Q2KJE0, Q3UKC1, Q3UPP8, Q498G2, Q4KLY0, Q4R703, Q4R7H3, Q5NVN6, Q5PR68, Q5R4U3, Q5U3Z6, Q5VU43, Q5ZJA3, Q62209, Q66HA4, Q66KE8, Q69ZB0, Q6NRC9, Q6P3P1, Q6TFL3, Q70FJ1, Q80UF4, Q80Z25, Q86SQ7

Diamond homologs: Q8TD10, Q9D9F8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MIPOL1	“up-regulates activity”	RHOB	binding
MIPOL1	“down-regulates activity”	AKT
MIPOL1	“down-regulates activity”	RELA

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

5207 predictions. Top by Δscore:

Variant	Effect	Δscore
14:37240570:G:GG	donor_gain	1.0000
14:37266933:TACA:T	acceptor_loss	1.0000
14:37266934:ACAG:A	acceptor_loss	1.0000
14:37266936:A:AC	acceptor_loss	1.0000
14:37266937:GA:G	acceptor_gain	1.0000
14:37266937:GAC:G	acceptor_gain	1.0000
14:37266937:GACAT:G	acceptor_gain	1.0000
14:37267170:G:GG	donor_gain	1.0000
14:37267750:T:G	acceptor_gain	1.0000
14:37268656:A:AG	acceptor_gain	1.0000
14:37268657:G:GG	acceptor_gain	1.0000
14:37268657:GC:G	acceptor_gain	1.0000
14:37268657:GCGTT:G	acceptor_gain	1.0000
14:37268789:AAAAG:A	donor_loss	1.0000
14:37268790:AAAG:A	donor_loss	1.0000
14:37268791:AAG:A	donor_loss	1.0000
14:37268792:AGGT:A	donor_loss	1.0000
14:37268793:GGTAT:G	donor_loss	1.0000
14:37268794:GTATA:G	donor_loss	1.0000
14:37268795:T:A	donor_loss	1.0000
14:37268805:A:T	donor_gain	1.0000
14:37285312:T:TA	acceptor_gain	1.0000
14:37285316:A:AG	acceptor_gain	1.0000
14:37285317:G:GG	acceptor_gain	1.0000
14:37285317:GCT:G	acceptor_gain	1.0000
14:37285431:G:GT	donor_gain	1.0000
14:37285443:AAAGT:A	donor_gain	1.0000
14:37285444:AAGT:A	donor_gain	1.0000
14:37285446:GT:G	donor_gain	1.0000
14:37285448:G:GG	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003634 (14:37362931 A>G), RS1000020282 (14:37581007 A>G), RS1000020864 (14:37334908 T>C,G), RS1000027370 (14:37422966 C>T), RS1000044800 (14:37581366 C>T), RS1000046242 (14:37487829 C>A,T), RS1000058250 (14:37490704 G>C,T), RS1000069497 (14:37355290 G>A,C,T), RS1000075454 (14:37277770 T>A), RS1000078183 (14:37406822 T>C), RS1000078473 (14:37487543 A>C,T), RS1000084733 (14:37543429 C>A,G), RS1000092065 (14:37235395 T>C), RS1000097018 (14:37575957 A>AG), RS1000100258 (14:37222301 C>A)

Disease associations

OMIM: gene MIM:606850 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002981_5	Longitudinal alcohol consumption	1.000000e-06
GCST003995_9	Tonsillectomy	8.000000e-13
GCST004602_177	Mean corpuscular volume	3.000000e-14
GCST004630_198	Mean corpuscular hemoglobin	8.000000e-15
GCST005014_96	Tonsillectomy	8.000000e-13
GCST005580_81	Intraocular pressure	2.000000e-11
GCST005580_88	Intraocular pressure	4.000000e-11
GCST008058_276	Estimated glomerular filtration rate	2.000000e-07
GCST009325_15	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	4.000000e-08
GCST009391_424	Metabolite levels	7.000000e-06
GCST90002382_223	Eosinophil percentage of white cells	6.000000e-11
GCST90002396_560	Mean reticulocyte volume	1.000000e-40
GCST90002403_504	Red blood cell count	1.000000e-15

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004695	intraocular pressure measurement
EFO:0010388	phosphatidylcholine 38:6 measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

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
Benzo(a)pyrene	decreases expression, decreases methylation	3
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
phenethyl isothiocyanate	affects binding	1
jinfukang	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Temozolomide	increases expression	1
Leflunomide	increases expression	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Clorgyline	increases expression	1
Endosulfan	decreases expression	1
Methotrexate	increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Vanadates	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin M1	decreases expression	1

Clinical trials (associated diseases)

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