KLF7

Summary

KLF7 (KLF transcription factor 7, HGNC:6350) is a protein-coding gene on chromosome 2q33.3, encoding Krueppel-like factor 7 (O75840). Transcriptional factor.

The protein encoded by this gene is a member of the Kruppel-like transcriptional regulator family. Members in this family regulate cell proliferation, differentiation and survival and contain three C2H2 zinc fingers at the C-terminus that mediate binding to GC-rich sites. This protein may contribute to the progression of type 2 diabetes by inhibiting insulin expression and secretion in pancreatic beta-cells and by deregulating adipocytokine secretion in adipocytes. A pseudogene of this gene is located on the long arm of chromosome 3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8609 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 82 total
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_003709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6350
Approved symbol	KLF7
Name	KLF transcription factor 7
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Aliases	UKLF
Ensembl gene	ENSG00000118263
Ensembl biotype	protein_coding
OMIM	604865
Entrez	8609

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000309446, ENST00000421199, ENST00000423015, ENST00000426163, ENST00000435602, ENST00000451244, ENST00000457962, ENST00000458272, ENST00000467833, ENST00000703689, ENST00000703733, ENST00000703734, ENST00000703735, ENST00000703736, ENST00000874448, ENST00000874449, ENST00000874450, ENST00000874451, ENST00000948505

RefSeq mRNA: 4 — MANE Select: NM_003709 NM_001270942, NM_001270943, NM_001270944, NM_003709

CCDS: CCDS2373, CCDS59438, CCDS59439, CCDS59440

Canonical transcript exons

ENST00000309446 — 4 exons

Exon	Start	End
ENSE00000934675	207123774	207124404
ENSE00001401308	207165467	207165948
ENSE00001854866	207074137	207081264
ENSE00003473020	207088458	207088581

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 96.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.5023 / max 747.5692, expressed in 1746 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33385	11.0941	1689
33382	10.0605	1528
33380	3.5108	1276
33367	1.9986	597
33384	1.4908	678
33386	1.3298	433
33379	0.7577	422
33383	0.5807	335
202549	0.3291	132
33381	0.2321	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.55	gold quality
cortical plate	UBERON:0005343	94.98	gold quality
saphenous vein	UBERON:0007318	92.12	gold quality
ganglionic eminence	UBERON:0004023	92.00	gold quality
calcaneal tendon	UBERON:0003701	91.48	gold quality
dorsal root ganglion	UBERON:0000044	90.72	gold quality
bone marrow cell	CL:0002092	90.33	gold quality
blood vessel layer	UBERON:0004797	89.89	gold quality
sural nerve	UBERON:0015488	89.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.31	gold quality
hair follicle	UBERON:0002073	88.90	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.71	gold quality
lower lobe of lung	UBERON:0008949	88.66	gold quality
blood	UBERON:0000178	88.49	gold quality
monocyte	CL:0000576	88.36	gold quality
tendon	UBERON:0000043	88.25	gold quality
mononuclear cell	CL:0000842	88.18	gold quality
renal glomerulus	UBERON:0000074	88.18	gold quality
metanephric glomerulus	UBERON:0004736	88.08	gold quality
leukocyte	CL:0000738	87.78	gold quality
visceral pleura	UBERON:0002401	87.18	gold quality
smooth muscle tissue	UBERON:0001135	87.12	gold quality
vena cava	UBERON:0004087	86.24	gold quality
pancreatic ductal cell	CL:0002079	86.13	silver quality
parietal pleura	UBERON:0002400	86.00	gold quality
superficial temporal artery	UBERON:0001614	85.86	gold quality
cardia of stomach	UBERON:0001162	85.85	gold quality
trigeminal ganglion	UBERON:0001675	85.84	gold quality
bone marrow	UBERON:0002371	85.83	gold quality
synovial joint	UBERON:0002217	85.76	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	28.43
E-ANND-3	yes	13.94
E-GEOD-124858	no	237.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
CDKN1A	Activation
CDKN1B
FABP7	Activation
FBXO38
HK2	Repression
INS	Repression
KLF7
NGF
NTRK1	Unknown
NTRK2
SLC13A4	Unknown

JASPAR motifs

Motif	Name	Family
MA1959.1	KLF7	Three-zinc finger Kruppel-related
MA1959.2	KLF7	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:28916725

Upstream regulators (CollecTRI, top): KLF7, MYC

miRNA regulators (miRDB)

294 targeting KLF7, 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-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049

Literature-anchored findings (GeneRIF, showing 36)

• KLF7 was upregulated by morphine at both the transcriptional and the translational levels, promoting cell growth up to day 4 (PMID:14644156)
• The gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes. (PMID:15937668)
• KLF7 may contribute to the pathogenesis of type 2 diabetes through an impairment of insulin biosynthesis and secretion in pancreatic beta-cells and a reduction of insulin sensitivity in peripheral tissues. (PMID:16339272)
• We identified a novel association between the minor A-allele of KLF7 and protection against obesity in the Danish population (PMID:19147600)
• a dominant mutation in FBXO38 causes adult-onset, progressive spinal muscular atrophy with calf predominance (PMID:24207122)
• Higher expression of TLR4 and KLF7 may play a vital role in the process of inflammation induced by obesity in visceral adipose tissue (PMID:27714571)
• Kruppel family member KLF7 promotes the corneal progenitor cell state; on many genes, KLF7 antagonized the corneal differentiation-promoting KLF4. (PMID:28916725)
• KLF7 has an important role in gastric cancer (GC) progression, as it inhibits GC cell migration and may serve as a prognostic marker (PMID:28977783)
• e report 4 unrelated individuals with de novo KLF7 missense variants who share similar clinical features of developmental delay/ID, hypotonia, feeding/swallowing issues, psychiatric features and neuromuscular symptoms, and add to the knowledge about the phenotypic spectrum associated with KLF7 haploinsufficiency. (PMID:29251763)
• Bioinformatics analysis and luciferase reporter gene assays revealed that Kruppel-like factor 7 (KLF7) was the target of miR-185. Overexpression of miR-185 reduced the expression of KLF7 in NSCLC cells. Upregulation of KLF7 partly neutralized the inhibitory effects of miR-185 on the proliferation and invasion of NSCLC. (PMID:29716672)
• KLF7 is decreased in women with polycystic ovary syndrome, but no significant association was observed between KLF7 and the BMI, total testosterone, and insulin resistance (PMID:30969076)
• Mechanistically, KLF7 transcriptionally activated argininosuccinate lyase (ASL), which was observed highly expressed in glioma tissues. KLF7 potentiates polyamine biosynthesis and glioma cell growth via transcriptionally activates ASL. (PMID:31018905)
• STAT3-induced LINC00668 contributed to non-small cell lung cancer progression through upregulating KLF7 expression by sponging miR-193a. (PMID:31150989)
• High Expression of Kruppel-like Factor 7 Indicates Unfavorable Clinical Outcomes in Patients with Lung Adenocarcinoma. (PMID:32092599)
• KLF7 promotes pancreatic cancer growth and metastasis by up-regulating ISG expression and maintaining Golgi complex integrity. (PMID:32430335)
• Elevated KLF7 levels may serve as a prognostic signature and might contribute to progression of squamous carcinoma. (PMID:32536035)
• KLF7 promotes macrophage activation by activating the NF-kappaB signaling pathway in epicardial adipose tissue in patients with coronary artery disease. (PMID:32633394)
• KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer. (PMID:33250051)
• KLF7 is associated with poor prognosis and regulates migration and adhesion in tongue cancer. (PMID:33393169)
• OSMRbeta mutants enhance basal keratinocyte differentiation via inactivation of the STAT5/KLF7 axis in PLCA patients. (PMID:33502684)
• GNA14 stimulation of KLF7 promotes malignant growth of endometrial cancer through upregulation of HAS2. (PMID:33892667)
• Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7. (PMID:34614499)
• LncRNA SNHG14 accelerates breast cancer progression through sponging miR-543 and regulating KLF7 expression. (PMID:34783894)
• Kruppel-like Transcription Factor 7 Is a Causal Gene in Autism Development. (PMID:35328799)
• Long noncoding RNA PVT1 regulates the proliferation and apoptosis of ARPE-19 cells in vitro via the miR-1301-3p/KLF7 axis. (PMID:35451342)
• Cancer-suppressing miR-520-3p gene inhibits proliferation, migration, and invasion of gastric cancer cells through targeted regulation of KLF7. (PMID:35465967)
• Kruppel-like factor 7 influences translation and pathways involved in ribosomal biogenesis in breast cancer. (PMID:36192788)
• LncRNA NUTM2A-AS1 aggravates the progression of hepatocellular carcinoma by activating the miR-186-5p/KLF7-mediated Wnt/beta-catenin pathway. (PMID:36242728)
• Circular hsa_circ_0020377 regulates KLF7 by targeting miR-194-5p to facilitate tumor cell malignant behaviors and glycolysis in oral squamous cell carcinoma progression. (PMID:36717528)
• Molecular function of Kruppel-like factor 7 in biology. (PMID:37227154)
• HMGB1-mediated elevation of KLF7 facilitates hepatocellular carcinoma progression and metastasis through upregulating TLR4 and PTK2. (PMID:37554278)
• KLF7 regulates super-enhancer-driven IGF2BP2 overexpression to promote the progression of head and neck squamous cell carcinoma. (PMID:38443991)
• UKLF/PCBP2 axis governs the colorectal cancer development by transcriptionally activating SLC39A4. (PMID:38768927)
• KLF7 promotes neuroblastoma differentiation through the GTPase signaling pathway by upregulating neuroblast differentiation-associated protein AHNAKs and glycerophosphodiesterase GDPD5. (PMID:38924469)
• KLF7 enhances the invasion and migration of colorectal cancer cells via the miR-139-5p/TPD52 axis. (PMID:39097779)
• Newborn adiposity is associated with cord blood DNA methylation at IGF1R and KLF7. (PMID:39165088)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf7b	ENSDARG00000043821
danio_rerio	klf7a	ENSDARG00000073857
mus_musculus	Klf7	ENSMUSG00000025959
rattus_norvegicus	Klf7	ENSRNOG00000046242
drosophila_melanogaster	luna	FBGN0040765

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), 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), KLF18 (ENSG00000283039)

Protein

Protein identifiers

Krueppel-like factor 7 — O75840 (reviewed: O75840)

Alternative names: Ubiquitous krueppel-like factor

All UniProt accessions (8): A0A994J3U4, A0A994J401, A0A994J6Y4, C9JX20, O75840, E7EQY2, E7EUU0, E9PHC9

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional factor. Plays a critical role in neuronal morphogenesis and survival of sensory neurons. Represses the corneal epithelium differentiation. Also acts as a metabolic regulator, by modulating insulin sensitivity in pancreatic beta cells and skeletal muscle cells. Inhibits transcriptional inducers of adipogenesis and has a repressive role in the expression of several adipokines, including leptin.

Subunit / interactions. Interacts with FBXO38.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Domain organisation. The acidic N-terminal part may favor interaction with the basic domain of transcription factors. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF7, the motif is inactive.

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

Isoforms (6)

UniProt ID	Names	Canonical?
O75840-1	1	yes
O75840-2	2
O75840-3	3
O75840-4	4
O75840-5	5
O75840-6	6

RefSeq proteins (4): NP_001257871, NP_001257872, NP_001257873, NP_003700* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (15 total): splice variant 6, zinc finger region 3, sequence variant 3, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75840-F1	55.46	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 528 (showing top): GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_INSULIN_SECRETION, GOZGIT_ESR1_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, LHX3_01

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), axonogenesis (GO:0007409), axon guidance (GO:0007411), glucose homeostasis (GO:0042593), regulation of epidermal cell differentiation (GO:0045604), positive regulation of transcription by RNA polymerase II (GO:0045944), dendrite morphogenesis (GO:0048813), negative regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061179), negative regulation of adipose tissue development (GO:1904178), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (8): 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), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
cell morphogenesis involved in neuron differentiation	2
neuron projection morphogenesis	2
negative regulation of DNA-templated transcription	1
axon development	1
axonogenesis	1
neuron projection guidance	1
carbohydrate homeostasis	1
epidermal cell differentiation	1
regulation of epithelial cell differentiation	1
regulation of epidermis development	1
positive regulation of DNA-templated transcription	1
dendrite development	1
insulin secretion involved in cellular response to glucose stimulus	1
negative regulation of insulin secretion	1
negative regulation of response to stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
adipose tissue development	1
regulation of adipose tissue development	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	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
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1

Protein interactions and networks

STRING

912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF7	FBXO38	Q6PIJ6	899
KLF7	RNH1	P13489	649
KLF7	SOX11	P35716	568
KLF7	NTRK1	P04629	499
KLF7	TBX3	O15119	494
KLF7	NHLH1	Q02575	484
KLF7	SOX2	P48431	456
KLF7	ZNF292	O60281	447
KLF7	LIN28A	Q9H9Z2	445
KLF7	POU5F1	P31359	443
KLF7	FBXO15	Q8NCQ5	442
KLF7	EBF1	Q9UH73	433
KLF7	SPRR2A	P35326	423
KLF7	PLAUR	Q03405	423
KLF7	NANOG	Q9H9S0	419

IntAct

5 interactions, top by confidence:

A	B	Type	Score
	KLF7	psi-mi:“MI:0915”(physical association)	0.370
IL1RN	KLF7	psi-mi:“MI:0915”(physical association)	0.370
TNFSF10	KLF7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (8): KLF7 (Affinity Capture-RNA), FBXO38 (Two-hybrid), KLF7 (Reconstituted Complex), FBXO38 (Affinity Capture-Western), KLF7 (Affinity Capture-Western), KLF7 (Affinity Capture-RNA), KLF7 (Affinity Capture-RNA), APP (Reconstituted Complex)

ESM2 similar proteins: A9ZPC9, O08584, O08876, O08954, O14901, O35739, O35819, O43623, O70343, O75840, O89091, P10244, P22227, P36197, P37275, P41182, P43300, P43301, P48972, P55878, P79288, P97469, Q01713, Q06889, Q4V7E1, Q5EXX3, Q5ZM39, Q60542, Q62947, Q64318, Q6DCW1, Q6NRM0, Q6XDT6, Q753Y2, Q804R0, Q865B7, Q8AWY2, Q8NAP3, Q8NCP5, Q8R0A2

Diamond homologs: O08584, O08876, O14901, O35738, O35819, O43474, O62259, O70494, O75840, O89090, O89091, O95600, P08047, P0CG40, P46099, P57682, P58334, Q01714, Q02446, Q02447, Q0VA40, Q13118, Q13351, Q13887, Q14V87, Q19A40, Q19A41, Q22678, Q24266, Q3SY56, Q5XGT8, Q60793, Q60843, Q60980, Q62445, Q64HY3, Q64HY5, Q65ZG6, Q6BEB4, Q6NW96

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FBXO38	“up-regulates activity”	KLF7	binding
KLF7	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	11
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1592 predictions. Top by Δscore:

Variant	Effect	Δscore
2:207124400:CATGT:C	acceptor_gain	1.0000
2:207124401:ATGT:A	acceptor_gain	1.0000
2:207124402:TGT:T	acceptor_gain	1.0000
2:207124402:TGTC:T	acceptor_loss	1.0000
2:207124403:GT:G	acceptor_gain	1.0000
2:207124403:GTC:G	acceptor_loss	1.0000
2:207124404:TCT:T	acceptor_loss	1.0000
2:207124405:C:A	acceptor_loss	1.0000
2:207124405:C:CC	acceptor_gain	1.0000
2:207124406:T:A	acceptor_loss	1.0000
2:207088449:T:TA	donor_gain	0.9900
2:207088578:TCACC:T	acceptor_loss	0.9900
2:207088579:CACCT:C	acceptor_loss	0.9900
2:207088583:T:C	acceptor_loss	0.9900
2:207124409:A:T	acceptor_gain	0.9900
2:207124750:A:AC	acceptor_gain	0.9900
2:207124750:A:C	acceptor_gain	0.9900
2:207165462:TTCAC:T	donor_loss	0.9900
2:207165463:TCAC:T	donor_loss	0.9900
2:207165464:CACC:C	donor_loss	0.9900
2:207165465:A:C	donor_loss	0.9900
2:207165466:C:CT	donor_loss	0.9900
2:207088577:CTCAC:C	acceptor_gain	0.9800
2:207088579:CAC:C	acceptor_gain	0.9800
2:207109583:C:CC	acceptor_gain	0.9800
2:207119040:TTTCC:T	donor_gain	0.9800
2:207124408:C:CT	acceptor_gain	0.9800
2:207124749:CA:C	acceptor_gain	0.9800
2:207165466:CCTG:C	donor_gain	0.9800
2:207088453:TTTA:T	donor_loss	0.9700

AlphaMissense

1965 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:207081258:A:C	F288L	1.000
2:207081258:A:T	F288L	1.000
2:207081260:A:G	F288L	1.000
2:207088474:A:G	C281R	1.000
2:207088535:A:C	F260L	1.000
2:207088535:A:T	F260L	1.000
2:207088537:A:G	F260L	1.000
2:207081231:G:C	H297Q	0.999
2:207081231:G:T	H297Q	0.999
2:207081241:A:G	L294P	0.999
2:207081259:A:G	F288S	0.999
2:207088473:C:G	C281S	0.999
2:207088474:A:T	C281S	0.999
2:207088478:G:C	F279L	0.999
2:207088478:G:T	F279L	0.999
2:207088480:A:G	F279L	0.999
2:207088496:G:C	H273Q	0.999
2:207088496:G:T	H273Q	0.999
2:207088498:G:C	H273D	0.999
2:207088502:C:A	R271S	0.999
2:207088502:C:G	R271S	0.999
2:207088508:G:C	H269Q	0.999
2:207088508:G:T	H269Q	0.999
2:207088510:G:C	H269D	0.999
2:207088518:A:G	L266P	0.999
2:207088536:A:G	F260S	0.999
2:207088562:G:C	C251W	0.999
2:207088563:C:G	C251S	0.999
2:207088564:A:G	C251R	0.999
2:207088564:A:T	C251S	0.999

dbSNP variants (sampled 300 via entrez): RS1000002541 (2:207094799 T>C), RS1000010961 (2:207142790 T>A), RS1000049011 (2:207098125 C>G), RS1000049233 (2:207101622 T>C), RS1000152695 (2:207095141 C>T), RS1000201499 (2:207153409 A>G), RS1000246771 (2:207088384 C>G,T), RS1000280167 (2:207154913 G>C), RS1000368139 (2:207107577 T>C), RS1000388096 (2:207107628 A>G), RS1000425011 (2:207136307 C>T), RS1000454168 (2:207101289 G>A,C,T), RS1000483614 (2:207148735 T>A,C), RS1000496212 (2:207131985 C>T), RS1000505220 (2:207106506 C>T)

Disease associations

OMIM: gene MIM:604865 | disease phenotypes: MIM:607834

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (3): neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), anxiety (MONDO:0011918)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST002913_1	Lachrymal/Salivary gland lesion in type 1 autoimmune pancreatitis	3.000000e-06
GCST004601_37	Red blood cell count	6.000000e-09
GCST004604_82	Hematocrit	5.000000e-11
GCST004615_7	Hemoglobin concentration	1.000000e-10
GCST006463_3	Urinary albumin excretion (no hypertensive medication)	5.000000e-08
GCST006620_1	Self-rated health	2.000000e-10
GCST006627_85	Diastolic blood pressure	5.000000e-09
GCST007327_27	Smoking status (ever vs never smokers)	3.000000e-08
GCST008948_1	Chromosomal aberration frequency (chromatid type) in genotoxic compound exposure	9.000000e-08
GCST010083_145	Hemoglobin levels	4.000000e-12
GCST011832_4	Pediatric central nervous system tumors (pleiotropy)	3.000000e-06
GCST012244_2	Childhood asthma exacerbations in long-acting beta2-agonist treatment	5.000000e-06
GCST90000025_867	Appendicular lean mass	6.000000e-13
GCST90002383_198	Hematocrit	1.000000e-19
GCST90002384_241	Hemoglobin	1.000000e-17
GCST90002401_394	Platelet distribution width	1.000000e-09
GCST90002403_121	Red blood cell count	5.000000e-14

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0007124	salivary gland lesion
EFO:0007125	lachrymal gland lesion
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004285	albuminuria
EFO:0004778	self rated health
EFO:0006336	diastolic blood pressure
EFO:0004318	smoking behavior
EFO:0009862	chromatid-type aberration frequency
EFO:0007614	asthma exacerbation measurement
EFO:0004980	appendicular lean mass
EFO:0007984	platelet component distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001007	Anxiety	F01.470.132
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Formaldehyde	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric oxide	increases expression	1
hydroquinone	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
vanadium pentoxide	increases expression	1
CGP 52608	affects binding, increases reaction	1
torcetrapib	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3R7	SEES3-1V human KLF7, clone1	Embryonic stem cell	Male
CVCL_A3R8	SEES3-1V human KLF7, clone2	Embryonic stem cell	Male
CVCL_A3R9	SEES3-1V human KLF7, clone3	Embryonic stem cell	Male
CVCL_E0G5	Ubigene HeLa KLF7 KO	Cancer cell line	Female
CVCL_F1P3	HyCyte HCT 116 KO-hKLF7	Cancer cell line	Male
CVCL_HC81	HEK293 eGFP-KLF7	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays