UNK

Summary

UNK (unk zinc finger, HGNC:29369) is a protein-coding gene on chromosome 17q25.1, encoding RING finger protein unkempt homolog (Q9C0B0). Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development.

Enables mRNA CDS binding activity. Involved in cell morphogenesis involved in neuron differentiation and negative regulation of cytoplasmic translation. Located in cytoplasm.

Source: NCBI Gene 85451 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_001080419

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29369
Approved symbol	UNK
Name	unk zinc finger
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1753
Ensembl gene	ENSG00000132478
Ensembl biotype	protein_coding
OMIM	616375
Entrez	85451

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000586217, ENST00000586527, ENST00000587258, ENST00000587501, ENST00000589666, ENST00000589790, ENST00000592074, ENST00000592629, ENST00000925668, ENST00000925669, ENST00000925670, ENST00000925671

RefSeq mRNA: 1 — MANE Select: NM_001080419 NM_001080419

CCDS: CCDS45778

Canonical transcript exons

ENST00000589666 — 16 exons

Exon	Start	End
ENSE00000905152	75818642	75818816
ENSE00001058536	75812112	75812288
ENSE00001117806	75819920	75820108
ENSE00001117807	75815169	75815253
ENSE00001117808	75818103	75818168
ENSE00001117811	75816770	75816912
ENSE00001117812	75823265	75823522
ENSE00001117814	75822477	75822658
ENSE00001117818	75819684	75819785
ENSE00001229552	75817326	75817526
ENSE00002785893	75824262	75825799
ENSE00002924949	75784806	75784984
ENSE00003463791	75812455	75812585
ENSE00003547224	75813761	75813878
ENSE00003551573	75813078	75813213
ENSE00003565275	75809760	75809969

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 93.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6411 / max 148.4644, expressed in 1806 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162800	21.6411	1806

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.56	gold quality
sural nerve	UBERON:0015488	93.10	gold quality
right uterine tube	UBERON:0001302	93.05	gold quality
kidney epithelium	UBERON:0004819	92.04	gold quality
left ovary	UBERON:0002119	91.69	gold quality
ventricular zone	UBERON:0003053	91.44	gold quality
right ovary	UBERON:0002118	91.38	gold quality
skin of leg	UBERON:0001511	91.31	gold quality
right testis	UBERON:0004534	91.21	gold quality
endocervix	UBERON:0000458	91.12	gold quality
body of uterus	UBERON:0009853	91.05	gold quality
ectocervix	UBERON:0012249	90.93	gold quality
right lobe of thyroid gland	UBERON:0001119	90.90	gold quality
pituitary gland	UBERON:0000007	90.87	gold quality
upper arm skin	UBERON:0004263	90.77	gold quality
left testis	UBERON:0004533	90.73	gold quality
adenohypophysis	UBERON:0002196	90.58	gold quality
skin of abdomen	UBERON:0001416	90.54	gold quality
zone of skin	UBERON:0000014	90.13	gold quality
left uterine tube	UBERON:0001303	89.79	gold quality
uterine cervix	UBERON:0000002	89.55	gold quality
left lobe of thyroid gland	UBERON:0001120	89.54	gold quality
minor salivary gland	UBERON:0001830	89.54	gold quality
tibial nerve	UBERON:0001323	89.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.49	gold quality
lower esophagus mucosa	UBERON:0035834	89.49	gold quality
ganglionic eminence	UBERON:0004023	89.48	gold quality
testis	UBERON:0000473	89.41	gold quality
adult organism	UBERON:0007023	89.37	gold quality
spleen	UBERON:0002106	89.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting UNK, 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-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	unk	ENSDARG00000000935
mus_musculus	Unk	ENSMUSG00000020770
rattus_norvegicus	Unk	ENSRNOG00000006600
drosophila_melanogaster	unk	FBGN0004395
caenorhabditis_elegans		WBGENE00016407

Paralogs (1): UNKL (ENSG00000059145)

Protein

Protein identifiers

RING finger protein unkempt homolog — Q9C0B0 (reviewed: Q9C0B0)

Alternative names: Zinc finger CCCH domain-containing protein 5

All UniProt accessions (6): Q9C0B0, K7EIZ1, K7ELF5, K7EMB1, K7EQ93, K7EQJ1

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes.

Subcellular location. Cytoplasm.

Similarity. Belongs to the unkempt family.

RefSeq proteins (1): NP_001073888* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR040594	UNK_Znf_1	Domain
IPR045234	Unkempt-like	Family
IPR057295	UNK_Znf_4	Domain
IPR057296	UNK_Znf_5	Domain

Pfam: PF00642, PF18384, PF23035, PF23261, PF25427

UniProt features (19 total): zinc finger region 6, modified residue 5, compositionally biased region 3, region of interest 3, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0B0-F1	66.84	0.37

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 (5): 240, 374, 378, 385, 631

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_NEURON_MIGRATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT, GOBP_REGULATION_OF_CYTOPLASMIC_TRANSLATION, BIDUS_METASTASIS_UP, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_REGULATION_OF_TRANSLATION, GOMF_MRNA_BINDING

GO Biological Process (5): in utero embryonic development (GO:0001701), neuron migration (GO:0001764), cell morphogenesis involved in neuron differentiation (GO:0048667), negative regulation of cytoplasmic translation (GO:2000766), regulation of translation (GO:0006417)

GO Molecular Function (5): RNA binding (GO:0003723), zinc ion binding (GO:0008270), ribosome binding (GO:0043022), mRNA CDS binding (GO:1990715), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	1
cell migration	1
generation of neurons	1
cell morphogenesis	1
neuron differentiation	1
neuron development	1
cytoplasmic translation	1
negative regulation of translation	1
regulation of cytoplasmic translation	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
transition metal ion binding	1
ribonucleoprotein complex binding	1
mRNA binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UNK	HLA-C	P04222	764
UNK	HLA-E	P13747	656
UNK	HLA-G	P17693	583
UNK	IL15	P40933	562
UNK	KIR2DL3	P43628	558
UNK	NCAM1	P13591	507
UNK	PGF	P49763	491
UNK	KLRD1	Q13241	462
UNK	HLA-A	P01891	460
UNK	KIR2DL4	P78400	455
UNK	NCR1	O76036	448
UNK	FCGR3A	P08637	447
UNK	FCGR3B	O75015	447
UNK	KLRC1	P26715	446
UNK	KIR2DL1	P43626	443

IntAct

20 interactions, top by confidence:

A	B	Type	Score
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
ACOT8	PML	psi-mi:“MI:0914”(association)	0.530
PABPC1	UNK	psi-mi:“MI:0407”(direct interaction)	0.440
CAMK2D	DVL2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
rep	PCNT	psi-mi:“MI:0914”(association)	0.350
SHANK3	IGKV3D-15	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
MDFI	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SIRT5	YEATS4	psi-mi:“MI:0914”(association)	0.350
CPEB1	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
UNK	PAX8	psi-mi:“MI:0915”(physical association)	0.000
ATXN1	UNK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (420): DPY30 (Affinity Capture-RNA), HINT1 (Affinity Capture-RNA), CALM2 (Affinity Capture-RNA), CLTC (Affinity Capture-RNA), USMG5 (Affinity Capture-RNA), ARF4 (Affinity Capture-RNA), GDI2 (Affinity Capture-RNA), MGST3 (Affinity Capture-RNA), TUBB (Affinity Capture-RNA), HSPA4 (Affinity Capture-RNA), CSDE1 (Affinity Capture-RNA), PPP2CA (Affinity Capture-RNA), CDC42 (Affinity Capture-RNA), EEF1A1 (Affinity Capture-RNA), CSE1L (Affinity Capture-RNA)

ESM2 similar proteins: A0A8M9QN10, A1A4L4, A7E2V4, A7E305, D4A039, E9Q0S6, O00750, O70405, O75385, P0C279, P59997, P70166, Q08E13, Q1LUT1, Q1LVK9, Q1LXR6, Q3UJB9, Q3UQI9, Q3UUF8, Q3ZAV8, Q4G0A6, Q52KN7, Q58D79, Q5DTV4, Q5R733, Q5RF72, Q5SSZ5, Q5XI59, Q64337, Q6A037, Q6EE22, Q6IRU7, Q6P1H6, Q6P2E9, Q6ZQF7, Q76LL6, Q7T2V3, Q7ZVP1, Q8BL48, Q8C008

Diamond homologs: O82199, O82307, Q5FWH2, Q6EE22, Q6L4N4, Q86B79, Q8BL48, Q9C0B0, Q9H9P5, Q9ZWA1, Q9FU27, Q9M0G2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	UNK	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3691 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75784985:G:GG	donor_gain	1.0000
17:75809931:G:GG	donor_gain	1.0000
17:75809965:GACGA:G	donor_gain	1.0000
17:75809968:GA:G	donor_gain	1.0000
17:75809970:G:GG	donor_gain	1.0000
17:75812110:A:AG	acceptor_gain	1.0000
17:75812111:G:GA	acceptor_loss	1.0000
17:75812111:G:GG	acceptor_gain	1.0000
17:75812450:CCCA:C	acceptor_loss	1.0000
17:75812451:CCAG:C	acceptor_loss	1.0000
17:75812453:A:AG	acceptor_gain	1.0000
17:75812453:AG:A	acceptor_gain	1.0000
17:75812454:G:GT	acceptor_gain	1.0000
17:75812454:GG:G	acceptor_gain	1.0000
17:75812454:GGGA:G	acceptor_gain	1.0000
17:75812579:TGGCA:T	donor_gain	1.0000
17:75812580:GGCAA:G	donor_gain	1.0000
17:75812581:GCAAG:G	donor_gain	1.0000
17:75812584:AGGT:A	donor_loss	1.0000
17:75812585:GGTAC:G	donor_loss	1.0000
17:75812586:G:C	donor_loss	1.0000
17:75812587:T:G	donor_loss	1.0000
17:75813073:T:TA	acceptor_gain	1.0000
17:75813076:A:AG	acceptor_gain	1.0000
17:75813077:G:GG	acceptor_gain	1.0000
17:75813077:GA:G	acceptor_gain	1.0000
17:75813199:G:GT	donor_gain	1.0000
17:75813211:CAG:C	donor_loss	1.0000
17:75813212:AGGT:A	donor_loss	1.0000
17:75813214:G:GA	donor_loss	1.0000

AlphaMissense

5279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75809765:T:C	L37P	1.000
17:75809773:T:C	F40L	1.000
17:75809774:T:C	F40S	1.000
17:75809774:T:G	F40C	1.000
17:75809775:C:A	F40L	1.000
17:75809775:C:G	F40L	1.000
17:75809776:C:A	R41S	1.000
17:75809776:C:G	R41G	1.000
17:75809777:G:C	R41P	1.000
17:75809788:T:A	C45S	1.000
17:75809788:T:C	C45R	1.000
17:75809789:G:A	C45Y	1.000
17:75809789:G:C	C45S	1.000
17:75809789:G:T	C45F	1.000
17:75809790:C:G	C45W	1.000
17:75809797:T:C	F48L	1.000
17:75809798:T:C	F48S	1.000
17:75809798:T:G	F48C	1.000
17:75809799:T:A	F48L	1.000
17:75809799:T:G	F48L	1.000
17:75809812:T:A	C53S	1.000
17:75809812:T:C	C53R	1.000
17:75809813:G:A	C53Y	1.000
17:75809813:G:C	C53S	1.000
17:75809813:G:T	C53F	1.000
17:75809814:C:G	C53W	1.000
17:75809836:T:A	C61S	1.000
17:75809836:T:C	C61R	1.000
17:75809837:G:A	C61Y	1.000
17:75809837:G:C	C61S	1.000

dbSNP variants (sampled 300 via entrez): RS1000085815 (17:75788397 C>A), RS1000110712 (17:75794586 C>T), RS1000114933 (17:75788668 T>C), RS1000168647 (17:75787942 C>T), RS1000171098 (17:75818528 C>A,T), RS1000209799 (17:75824067 G>A), RS1000271520 (17:75824887 C>G), RS1000297210 (17:75783169 C>T), RS1000324403 (17:75811444 A>T), RS1000327861 (17:75824508 A>G), RS1000384189 (17:75795265 G>A), RS1000453310 (17:75788849 G>C), RS1000467229 (17:75818318 AG>A,AGG), RS1000505366 (17:75789235 T>C,G), RS1000523275 (17:75818857 T>G)

Disease associations

OMIM: gene MIM:616375 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004606_28	Eosinophil count	3.000000e-09
GCST004624_10	Sum eosinophil basophil counts	8.000000e-10
GCST006612_25	LDL cholesterol	2.000000e-08
GCST009150_14	Low density lipoprotein cholesterol levels	3.000000e-22
GCST009597_204	Multiple sclerosis	7.000000e-06
GCST90002381_541	Eosinophil count	1.000000e-14
GCST90002382_481	Eosinophil percentage of white cells	2.000000e-10
GCST90002397_586	Mean spheric corpuscular volume	5.000000e-11
GCST90011898_83	Alanine aminotransferase levels	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007991	eosinophil percentage of leukocytes

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 cotreatment, decreases expression	5
Smoke	decreases expression, decreases reaction	2
Tobacco Smoke Pollution	decreases expression	2
FR900359	increases phosphorylation	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	decreases expression, decreases reaction	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Ribonucleotides	affects binding	1
Dronabinol	increases expression	1
Cyclosporine	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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