ZNF268

Summary

ZNF268 (zinc finger protein 268, HGNC:13061) is a protein-coding gene on chromosome 12q24.33, encoding Zinc finger protein 268 (Q14587). Acts as a transcriptional repressor.

Predicted to enable DNA binding activity and DNA-binding transcription factor activity. Involved in several processes, including positive regulation of non-canonical NF-kappaB signal transduction; regulation of apoptotic process; and regulation of primary metabolic process. Located in cytosol and nucleus.

Source: NCBI Gene 10795 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 175 total
• MANE Select transcript: NM_003415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13061
Approved symbol	ZNF268
Name	zinc finger protein 268
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	HZF3
Ensembl gene	ENSG00000090612
Ensembl biotype	protein_coding
OMIM	604753
Entrez	10795

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000228289, ENST00000416488, ENST00000500625, ENST00000534953, ENST00000536435, ENST00000536899, ENST00000537973, ENST00000539248, ENST00000541009, ENST00000541211, ENST00000541975, ENST00000542711, ENST00000542986, ENST00000546126, ENST00000585488, ENST00000588312, ENST00000591951, ENST00000592241, ENST00000611984, ENST00000885506, ENST00000885507, ENST00000937514

RefSeq mRNA: 9 — MANE Select: NM_003415 NM_001165881, NM_001165882, NM_001165883, NM_001165884, NM_001165885, NM_001165886, NM_001165887, NM_003415, NM_152943

CCDS: CCDS45012, CCDS53851, CCDS53852, CCDS53853, CCDS53854, CCDS59239, CCDS59240

Canonical transcript exons

ENST00000536435 — 6 exons

Exon	Start	End
ENSE00002957617	133202144	133214832
ENSE00003495048	133191908	133192003
ENSE00003584348	133187872	133188072
ENSE00003595282	133191489	133191615
ENSE00003734567	133181946	133182030
ENSE00003900710	133181495	133181686

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 88.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7240 / max 108.5483, expressed in 1776 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128860	8.6934	1749
128861	2.0306	1109

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	88.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.87	gold quality
choroid plexus epithelium	UBERON:0003911	87.43	gold quality
calcaneal tendon	UBERON:0003701	85.75	gold quality
cortical plate	UBERON:0005343	84.82	gold quality
ventricular zone	UBERON:0003053	84.63	gold quality
ganglionic eminence	UBERON:0004023	83.15	gold quality
buccal mucosa cell	CL:0002336	83.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.97	gold quality
pigmented layer of retina	UBERON:0001782	82.86	gold quality
islet of Langerhans	UBERON:0000006	82.33	gold quality
colonic epithelium	UBERON:0000397	81.73	gold quality
stromal cell of endometrium	CL:0002255	80.52	gold quality
oocyte	CL:0000023	80.18	gold quality
embryo	UBERON:0000922	80.11	gold quality
palpebral conjunctiva	UBERON:0001812	79.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.53	gold quality
blood vessel layer	UBERON:0004797	79.27	gold quality
secondary oocyte	CL:0000655	78.65	gold quality
endometrium	UBERON:0001295	78.60	gold quality
visceral pleura	UBERON:0002401	78.20	gold quality
germinal epithelium of ovary	UBERON:0001304	77.93	gold quality
rectum	UBERON:0001052	77.52	gold quality
tonsil	UBERON:0002372	77.42	gold quality
pleura	UBERON:0000977	77.34	gold quality
parietal pleura	UBERON:0002400	77.32	gold quality
gall bladder	UBERON:0002110	77.29	gold quality
adrenal gland	UBERON:0002369	77.17	gold quality
placenta	UBERON:0001987	76.76	gold quality
pancreas	UBERON:0001264	76.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.32

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CNTN2
UPF1
ZNF268

Upstream regulators (CollecTRI, top): CEBPA, CREB1, GATA1, KLF13, STAT1, ZNF268

miRNA regulators (miRDB)

241 targeting ZNF268, 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-188-3P	100.00	68.76	1240
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939

Literature-anchored findings (GeneRIF, showing 13)

• This protein has a conserved KRAB domain which localizes to the nucleus and has transcriptional repressor activity. (PMID:12822888)
• ZNF268 plays a role in early human liver development most likely by functioning through a cytoplasmic mechanism (PMID:15547661)
• 4 alternative transcripts of ZNF268 were detected in the human blood cells. (PMID:16735226)
• ZNF268 gene promoter is atypical and requires an intragenic element located within the first exon that mediates the effect of CREB for its activity (PMID:16787922)
• ZNF268 gene may function as a transcriptional activator in the growth and differentiation of cells in development and/or pathogenesis. (PMID:16865230)
• HTLV-1 oncoprotein tax represses ZNF268 expression through the cAMP-responsive element-binding (PMID:18375384)
• results indicate that a spliced form of ZNF268 lacking the KRAB domain is located in the cytosol, where it seems to play a role in TNF-alpha-induced NF-kappaB activation by interacting with the IKK complex. (PMID:18677094)
• Results demonstrate that the mammalian gene ZNF268 is regulated by hUpf1 via its promoter. (PMID:18774934)
• aberrant alternative splicing of ZNF268 is a potential prognostic factor of and may contribute to human hematological malignancies. (PMID:18949428)
• ZNF268 is a crucial downstream target and effector of GATA-1 (PMID:22235304)
• These results reveal a novel role of ZNF268b2 that contributes to cervical carcinogenesis in part through enhancing NF-kappaB signaling. (PMID:23091055)
• The nuclear localization activity of KRAB domain is a conserved feature of ZNF268. (PMID:23665872)
• KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly. (PMID:31835635)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631), ZNF3 (ENSG00000166526)

Protein

Protein identifiers

Zinc finger protein 268 — Q14587 (reviewed: Q14587)

Alternative names: Zinc finger protein HZF3

All UniProt accessions (13): Q14587, A0A075B6T9, A0A087WV54, E7EV44, F5H1T2, F5H467, F5H670, F5H6R9, F5H7L3, F5H848, K7EIF0, K7EMS6, K7EQP6

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional repressor. Inhibits erythroid differentiation and tumor cell proliferation. Plays a role during ovarian cancer development and progression. Contributes to cervical carcinogenesis in part through the TNF-induced NF-kappa-B signaling pathway by interacting with the I-kappa-B-kinase (IKK) core complex. Involved in the regulation of antiviral interferon signaling. During viral infection, recruits SETD4 to TBK1, leading to TBK1 monomethylation, which is critical for the assembly of TBK1 complex and IRF3 signaling.

Subunit / interactions. Interacts (via the KRAB domain) with TRIM28 (via the RBCC domain); the interaction increases ZNF268 nuclear localization activity. Isoform 2 interacts with CHUK and IKBKB; the interaction is further increased in a TNF-dependent manner. Interacts with TOLLIP; this interaction is impaired by ZNF268 phosphorylation at Ser-178. Forms a ternary complex with TBK1 and SETD4; the interaction between SETD4 and TBK1 is ZNF268-dependent and leads to TBK1 monomethylation.

Subcellular location. Nucleus Nucleus. Cytoplasm Cytoplasm.

Tissue specificity. Overexpressed in ovarian cancer tissues compared to normal ovarian tissues. Isoform 1 and isoform 2 are expressed in squamous epithelium tissues. Isoform 2 is overexpressed in squamous cervical cancer (at protein level). Expressed in blood cells. Isoform 1 is expressed in pancreas, lung, skeletal muscle, heart, placenta, liver, kidney and brain. Isoform 2 expressed in chronic lymphocytic leukemia (CLL) and several tumor cell lines. Isoform 3 is expressed in several tumor cells. Isoform 5 is expressed in fetal liver and several tumor cells. Isoform 6 is weakly expressed in brain, lung amd small intestin and in several tumor cells. Isoform 7 is expressed in fetal liver and several tumor cells.

Post-translational modifications. Phosphorylation at Ser-178 stabilizes the protein by interfering with its binding to TOLLIP, hence impairing its degradation by Tollip-mediated selective autophagy system.

Domain organisation. The KRAB domain functions to reinforce the nuclear localization of isoform 1 in addition to its transcription repression activity.

Induction. Down-regulated during erythroid differentiation by GATA1. Down-regulated by HTLV-1 Tax through the CREB/ATF pathway. Up-regulated by the regulator of nonsense transcript UPF1. Up-regulated by the cyclic AMP-dependent transcription factor ATF4.

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

Isoforms (7)

UniProt ID	Names	Canonical?
Q14587-1	1, ZNF268a, KW-4 variant-1	yes
Q14587-2	2, ZNF268s, KW-4 variant-2
Q14587-3	3, ZNF268c
Q14587-4	4, ZNF268d
Q14587-6	5, ZNF268e
Q14587-7	6, ZNF268f
Q14587-8	7, ZNF268g

RefSeq proteins (9): NP_001159353, NP_001159354, NP_001159355, NP_001159356, NP_001159357, NP_001159358, NP_001159359, NP_003406, NP_694422 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050758	Znf_C2H2-type	Family
IPR056436	Znf-C2H2_ZIC1-5/GLI1-3-like	Domain

Pfam: PF00096, PF01352, PF23561

UniProt features (147 total): strand 48, helix 27, zinc finger region 24, turn 16, splice variant 12, mutagenesis site 9, sequence conflict 7, chain 1, domain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
2EL4	SOLUTION NMR
2EL5	SOLUTION NMR
2EL6	SOLUTION NMR
2EM1	SOLUTION NMR
2EMV	SOLUTION NMR
2EMW	SOLUTION NMR
2EMX	SOLUTION NMR
2EMY	SOLUTION NMR
2EN0	SOLUTION NMR
2EN6	SOLUTION NMR
2EN7	SOLUTION NMR
2EOF	SOLUTION NMR
2EOG	SOLUTION NMR
2EOI	SOLUTION NMR
2EOJ	SOLUTION NMR
2EOK	SOLUTION NMR
2EOL	SOLUTION NMR
2EOP	SOLUTION NMR
2EPV	SOLUTION NMR
2EPW	SOLUTION NMR
2EPY	SOLUTION NMR
2YTF	SOLUTION NMR
2YTQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14587-F1	68.62	0.01

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 (1): 178

Mutagenesis-validated functional residues (9):

Position	Phenotype
85	strongly reduces nuclear localization and interaction with trim28; when associated with a-86.
86	reduces nuclear localization. strongly reduces nuclear localization and interaction with trim28; when associated with a-
88	reduces nuclear localization.
90	reduces nuclear localization.
93	reduces nuclear localization. strongly reduces nuclear localization; when associated with a-94 and a-95.
94	reduces nuclear localization. inhibits nuclear localization; when associated with a-93 and a-95.
95	reduces nuclear localization. inhibits nuclear localization; when associated with a-93 and a-94.
178	loss of phosphorylation by tbk1.
178	loss of interaction with tollip.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 184 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (20): negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of protein phosphorylation (GO:0001934), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), regulation of mitotic cell cycle (GO:0007346), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), cell differentiation (GO:0030154), positive regulation of cell migration (GO:0030335), regulation of protein catabolic process (GO:0042176), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of cell differentiation (GO:0045597), positive regulation of protein catabolic process (GO:0045732), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of cell cycle (GO:0051726), cellular response to tumor necrosis factor (GO:0071356), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), positive regulation of biosynthetic process (GO:0009891), regulation of cell differentiation (GO:0045595)

GO Molecular Function (5): DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
cell population proliferation	2
regulation of cell population proliferation	2
positive regulation of cellular process	2
protein catabolic process	2
apoptotic process	2
regulation of apoptotic process	2
cell differentiation	2
regulation of cellular process	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
mitotic cell cycle	1
regulation of cell cycle	1
negative regulation of cellular process	1
cellular developmental process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of catabolic process	1
regulation of protein metabolic process	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
regulation of cell differentiation	1
positive regulation of developmental process	1
positive regulation of catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
positive regulation of DNA-templated transcription	1
cell cycle	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF268	LGALS16	A8MUM7	408
ZNF268	MYEOV	Q96EZ4	369
ZNF268	CLC	Q05315	353
ZNF268	SETDB1	Q15047	332
ZNF268	EIF2S3	P41091	309
ZNF268	RINL	Q6ZS11	308
ZNF268	EFCAB13	Q8IY85	268
ZNF268	NAA38	Q9BRA0	257
ZNF268	TSTD1	Q8NFU3	246
ZNF268	TRIM28	Q13263	230
ZNF268	ABHD14A	Q9BUJ0	229
ZNF268	ZNRF4	Q8WWF5	223
ZNF268	ZMIZ2	Q8NF64	222
ZNF268	SFTA2	Q6UW10	220
ZNF268	NR3C1	P04150	204

IntAct

14 interactions, top by confidence:

A	B	Type	Score
RBPJ	NOTCH1	psi-mi:“MI:0914”(association)	0.910
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
TRIM28	ZNF320	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
SLC9A8	ZNF432	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
KRT40	ANKRD36	psi-mi:“MI:0914”(association)	0.350
EDAR	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
MRFAP1L1	MYO9A	psi-mi:“MI:0914”(association)	0.350
OTUD3	MLF1	psi-mi:“MI:0914”(association)	0.350
SLC9A8	AP1G1	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Negative Genetic), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS), ZNF268 (Affinity Capture-MS)

ESM2 similar proteins: A2VDQ7, A6NNF4, A8MQ14, A8MTY0, E9QAG8, O75290, O75373, P08043, P0CJ79, P10751, P17017, P17027, P17039, P35789, P51522, P51523, Q08AN1, Q14585, Q14587, Q3SYV7, Q3ZCX4, Q4R4C7, Q52M93, Q5MCW4, Q5R5U3, Q5R8X1, Q5R9F0, Q5SXM1, Q6ECI4, Q6JLC9, Q6P3V2, Q6P5C7, Q6ZN57, Q86UE3, Q86XN6, Q86YE8, Q8C827, Q8IYB9, Q8N4W9, Q8N7M2

Diamond homologs: A0JPL0, A2VDP4, A6QLU5, A6QPT6, A8MQ14, A8MUZ8, A8MWA4, B1APH4, B2RXC5, E9PYI1, E9Q8G5, O75290, O94892, P08042, P0CH99, P0CI00, P17014, P17025, P17030, P17031, P17032, P17098, P21506, P51508, P51523, P51786, P51814, P52736, P52738, Q02525, Q03923, Q03936, Q06730, Q06732, Q0VCB0, Q13401, Q14587, Q16587, Q2M218, Q2M3X9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GATA1	“down-regulates quantity by repression”	ZNF268	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1360 predictions. Top by Δscore:

Variant	Effect	Δscore
12:133181944:A:AG	acceptor_gain	1.0000
12:133181945:G:GG	acceptor_gain	1.0000
12:133181945:GC:G	acceptor_gain	1.0000
12:133182029:GG:G	donor_gain	1.0000
12:133182030:GG:G	donor_gain	1.0000
12:133182031:G:GG	donor_gain	1.0000
12:133182031:GT:G	donor_loss	1.0000
12:133182032:T:A	donor_loss	1.0000
12:133192004:G:GG	donor_gain	1.0000
12:133181625:G:GT	donor_gain	0.9900
12:133181634:G:GT	donor_gain	0.9900
12:133181684:G:GT	donor_gain	0.9900
12:133181704:TTTC:T	donor_gain	0.9900
12:133181718:G:GT	donor_gain	0.9900
12:133182026:TTTGG:T	donor_gain	0.9900
12:133182027:TTGG:T	donor_gain	0.9900
12:133182028:TGGG:T	donor_loss	0.9900
12:133182033:GAG:G	donor_loss	0.9900
12:133191517:T:TA	acceptor_gain	0.9900
12:133191525:ACCT:A	acceptor_gain	0.9900
12:133191525:ACCTG:A	acceptor_gain	0.9900
12:133191528:T:TA	acceptor_gain	0.9900
12:133191612:CTAGG:C	donor_loss	0.9900
12:133191613:TAGGT:T	donor_loss	0.9900
12:133191614:AGG:A	donor_loss	0.9900
12:133191615:GGT:G	donor_loss	0.9900
12:133191616:G:GT	donor_loss	0.9900
12:133191616:GT:G	donor_loss	0.9900
12:133191617:T:A	donor_loss	0.9900
12:133191617:T:G	donor_loss	0.9900

AlphaMissense

6336 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:133203547:T:C	F621L	0.999
12:133203549:T:A	F621L	0.999
12:133203549:T:G	F621L	0.999
12:133203566:T:C	L627P	0.999
12:133203799:T:C	F705L	0.999
12:133203801:C:A	F705L	0.999
12:133203801:C:G	F705L	0.999
12:133203379:T:C	F565L	0.998
12:133203381:C:A	F565L	0.998
12:133203381:C:G	F565L	0.998
12:133203818:T:C	L711P	0.998
12:133203398:T:C	L571P	0.997
12:133203463:T:C	F593L	0.997
12:133203465:T:A	F593L	0.997
12:133203465:T:G	F593L	0.997
12:133203482:T:C	L599P	0.997
12:133203631:T:C	F649L	0.997
12:133203633:T:A	F649L	0.997
12:133203633:T:G	F649L	0.997
12:133203883:T:C	F733L	0.997
12:133203885:T:A	F733L	0.997
12:133203885:T:G	F733L	0.997
12:133203902:T:C	L739P	0.997
12:133203967:T:C	F761L	0.997
12:133203969:T:A	F761L	0.997
12:133203969:T:G	F761L	0.997
12:133204051:T:C	F789L	0.997
12:133204053:T:A	F789L	0.997
12:133204053:T:G	F789L	0.997
12:133202959:T:C	F425L	0.996

dbSNP variants (sampled 300 via entrez): RS1000187965 (12:133205749 C>T), RS1000220063 (12:133200731 C>G,T), RS1000289767 (12:133201773 T>C), RS1000303086 (12:133192387 C>A,T), RS1000327370 (12:133192188 T>A,G), RS1000339883 (12:133212537 A>G), RS1000363311 (12:133195917 T>C,G), RS1000465547 (12:133196253 C>G,T), RS1000593518 (12:133200959 T>G), RS1000699643 (12:133197397 A>G), RS1000753346 (12:133197632 G>C,T), RS1000832487 (12:133180890 C>A), RS1000878073 (12:133188016 A>G), RS1000942511 (12:133182604 A>G), RS1000973737 (12:133182289 A>G)

Disease associations

OMIM: gene MIM:604753 | 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
GCST010002_179	Refractive error	1.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	5
Valproic Acid	affects expression, decreases expression	4
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	3
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
avobenzone	decreases expression	1
JP8 aviation fuel	increases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Progesterone	increases expression	1
Smoke	decreases expression, increases abundance	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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