KLF18

Summary

KLF18 (KLF transcription factor 18, HGNC:51793) is a protein-coding gene on chromosome 1p34.1, encoding Kruppel-like factor 18 (A0A0U1RQI7).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus.

Source: NCBI Gene 105378952 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_001358438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:51793
Approved symbol	KLF18
Name	KLF transcription factor 18
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000283039
Ensembl biotype	protein_coding
OMIM	621009
Entrez	105378952

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000634670

RefSeq mRNA: 1 — MANE Select: NM_001358438 NM_001358438

CCDS: CCDS85967

Canonical transcript exons

ENST00000634670 — 2 exons

Exon	Start	End
ENSE00001714047	44137821	44138011
ENSE00003786506	44138664	44141631

Expression profiles

Bgee: expression breadth tissue_specific, 6 present calls, max score 76.83.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.83	gold quality
kidney epithelium	UBERON:0004819	76.09	gold quality
upper arm skin	UBERON:0004263	73.97	gold quality
cardiac muscle of right atrium	UBERON:0003379	72.35	gold quality
left ventricle myocardium	UBERON:0006566	72.24	gold quality
pancreatic ductal cell	CL:0002079	71.88	silver quality
epithelial cell of pancreas	CL:0000083	70.18	gold quality
buccal mucosa cell	CL:0002336	65.94	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	63.62	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.43	gold quality
epithelium of nasopharynx	UBERON:0001951	62.43	gold quality
superficial temporal artery	UBERON:0001614	62.28	gold quality
quadriceps femoris	UBERON:0001377	61.65	gold quality
mammary duct	UBERON:0001765	61.65	gold quality
epithelium of mammary gland	UBERON:0003244	61.62	gold quality
vastus lateralis	UBERON:0001379	61.02	gold quality
biceps brachii	UBERON:0001507	60.74	gold quality
myocardium	UBERON:0002349	59.84	gold quality
mucosa of paranasal sinus	UBERON:0005030	58.07	gold quality
tibialis anterior	UBERON:0001385	58.03	silver quality
deltoid	UBERON:0001476	56.79	gold quality
nasal cavity epithelium	UBERON:0005384	56.62	gold quality
layer of synovial tissue	UBERON:0007616	54.45	gold quality
lower lobe of lung	UBERON:0008949	53.70	silver quality
inferior vagus X ganglion	UBERON:0005363	53.29	gold quality
upper leg skin	UBERON:0004262	53.17	gold quality
urethra	UBERON:0000057	52.87	gold quality
saphenous vein	UBERON:0007318	52.55	gold quality
subthalamic nucleus	UBERON:0001906	52.47	gold quality
pericardium	UBERON:0002407	52.41	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf1	ENSDARG00000017400
danio_rerio	klf5l	ENSDARG00000018757
danio_rerio	klf17	ENSDARG00000038792
danio_rerio	klf2b	ENSDARG00000040432
danio_rerio	klf2a	ENSDARG00000042667
danio_rerio	klf13	ENSDARG00000061368
danio_rerio	zgc:153115	ENSDARG00000069342
danio_rerio	si:ch211-117k10.3	ENSDARG00000090914
danio_rerio	sp5l	ENSDARG00000115868
mus_musculus	Zfp352	ENSMUSG00000070902
rattus_norvegicus	Zfp352	ENSRNOG00000033600
rattus_norvegicus	Zfp353	ENSRNOG00000050804
drosophila_melanogaster	Klf15	FBGN0025679
drosophila_melanogaster	CG3065	FBGN0034946
drosophila_melanogaster	luna	FBGN0040765
drosophila_melanogaster	CG42741	FBGN0261705
drosophila_melanogaster	dar1	FBGN0263239
caenorhabditis_elegans		WBGENE00018990

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), KLF15 (ENSG00000163884), SP8 (ENSG00000164651), KLF13 (ENSG00000169926), SP7 (ENSG00000170374), KLF17 (ENSG00000171872), KLF11 (ENSG00000172059), SP6 (ENSG00000189120), SP5 (ENSG00000204335), SP9 (ENSG00000217236), KLF14 (ENSG00000266265)

Protein

Protein identifiers

Kruppel-like factor 18 — A0A0U1RQI7 (reviewed: A0A0U1RQI7)

All UniProt accessions (1): A0A0U1RQI7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_001345367* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011049	Serralysin-like_metalloprot_C	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (4 total): zinc finger region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A0U1RQI7-F1	57.76	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): chr1p34, MATSUDA_NATURAL_KILLER_DIFFERENTIATION, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, PILON_KLF1_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_RNA_METABOLIC_PROCESS, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF18	CCDC24	Q8N4L8	451
KLF18	SIN3A	Q96ST3	430
KLF18	ERI3	O43414	364
KLF18	RNF220	Q5VTB9	358
KLF18	B4GALT2	O60909	305
KLF18	CTBP1	Q13363	275
KLF18	DMAP1	Q9NPF5	257
KLF18	KLF8	O95600	247
KLF18	SLC6A9	P48067	246
KLF18	KLF10	Q13118	231
KLF18	CTBP2	P56545	231
KLF18	SP9	P0CG40	219
KLF18	KLF14	Q8TD94	214
KLF18	KLF11	O14901	205
KLF18	NR1I2	O75469	205

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A023PXQ4, A0A0U1RQI7, A6NJU9, A6NNC1, A8MRT5, A8MUU9, C9JG80, E2RYF6, E5RHQ5, F8W0I5, O13534, O59779, P08399, P0C732, P0C785, P0DTH6, P0DW28, P13208, P15941, P21787, P24856, P39564, P51861, P87269, Q00130, Q01456, Q12444, Q13117, Q1HVI8, Q27905, Q2EEQ3, Q4ZJY7, Q4ZJZ0, Q5SDL7, Q63661, Q69577, Q6B0Y1, Q6RY98, Q6ZQT0, Q6ZRX8

Diamond homologs: A0A0U1RQI7, C7EMF5, Q00453, Q5JT82, Q8CFA7, O35738, O35819, Q19A41, Q60843, Q9ET58, Q9TZ64, Q9VZN4, Q9Y4X4, O14901, P03001, P08047, P17842, P22227, P31509, P34694, P34695, P79797, Q02026, Q02027, Q22678, Q59KL6, Q8VHT7, Q8VHT8, Q92664, Q9BXK1, Q9Y5W3, O62651, P19544, P22561, P49952, P49953, P50902, O08876, O43474, O89091

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

102 predictions. Top by Δscore:

Variant	Effect	Δscore
1:44138018:C:CT	acceptor_gain	0.9800
1:44138019:A:T	acceptor_gain	0.9700
1:44138656:TCAC:T	donor_loss	0.9400
1:44138657:CACT:C	donor_loss	0.9400
1:44138658:ACTC:A	donor_loss	0.9400
1:44138659:CT:C	donor_loss	0.9400
1:44138660:T:TC	donor_loss	0.9400
1:44138661:C:CC	donor_loss	0.9400
1:44138662:A:AG	donor_loss	0.9400
1:44138008:TCCCC:T	acceptor_loss	0.8900
1:44138010:CC:C	acceptor_gain	0.8900
1:44138011:CC:C	acceptor_gain	0.8900
1:44138011:CCTGG:C	acceptor_loss	0.8900
1:44138013:T:C	acceptor_loss	0.8900
1:44138662:A:AC	donor_gain	0.8900
1:44138663:C:CC	donor_gain	0.8900
1:44138012:C:CC	acceptor_gain	0.8700
1:44138009:CCC:C	acceptor_gain	0.8400
1:44138010:CCC:C	acceptor_gain	0.8400
1:44138018:C:T	acceptor_gain	0.8300
1:44138007:CTCCC:C	acceptor_gain	0.8000
1:44138663:CCGGT:C	donor_gain	0.8000
1:44138022:C:CT	acceptor_gain	0.7900
1:44138826:T:C	acceptor_gain	0.7800
1:44138658:A:AC	donor_gain	0.7500
1:44138659:C:CC	donor_gain	0.7500
1:44138663:CCG:C	donor_gain	0.7500
1:44138663:CCGG:C	donor_gain	0.7500
1:44138662:AC:A	donor_gain	0.7200
1:44138663:CC:C	donor_gain	0.7200

AlphaMissense

7012 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44137881:A:C	F1033L	0.999
1:44137881:A:T	F1033L	0.999
1:44137883:A:G	F1033L	0.999
1:44137965:A:C	F1005L	0.999
1:44137965:A:T	F1005L	0.999
1:44137967:A:G	F1005L	0.999
1:44137994:A:G	C996R	0.999
1:44137940:G:C	H1014D	0.998
1:44137978:C:G	C1001S	0.998
1:44137979:A:G	C1001R	0.998
1:44137979:A:T	C1001S	0.998
1:44137993:C:G	C996S	0.998
1:44137994:A:T	C996S	0.998
1:44137864:A:G	L1039P	0.997
1:44137893:G:C	C1029W	0.997
1:44137895:A:G	C1029R	0.997
1:44137904:A:G	C1026R	0.997
1:44137926:G:C	H1018Q	0.997
1:44137926:G:T	H1018Q	0.997
1:44137938:G:C	H1014Q	0.997
1:44137938:G:T	H1014Q	0.997
1:44137948:A:G	L1011P	0.997
1:44137966:A:G	F1005S	0.997
1:44137977:A:C	C1001W	0.997
1:44137992:G:C	C996W	0.997
1:44137993:C:T	C996Y	0.997
1:44137854:A:C	H1042Q	0.996
1:44137854:A:T	H1042Q	0.996
1:44137882:A:G	F1033S	0.996
1:44137894:C:G	C1029S	0.996

dbSNP variants (sampled 300 via entrez): RS1000062234 (1:44138382 G>A), RS1000685278 (1:44138149 T>C,G), RS1000968986 (1:44138913 G>A,T), RS1001000060 (1:44138571 C>T), RS1001180867 (1:44137901 A>C,G,T), RS1001252967 (1:44138090 C>A,T), RS1001740810 (1:44138570 C>A), RS1002208231 (1:44139283 C>A,G), RS1002503282 (1:44141305 T>A,C,G), RS1002667045 (1:44139532 C>T), RS1003618384 (1:44140874 G>A), RS1004011936 (1:44137437 A>T), RS1004077569 (1:44143145 C>A,T), RS1004450472 (1:44143519 A>G), RS1004665621 (1:44143381 C>A,T)

Disease associations

OMIM: gene MIM:621009 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Copper	decreases expression, affects cotreatment	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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