ZFP91

Summary

ZFP91 (ZFP91 zinc finger protein, atypical E3 ubiquitin ligase, HGNC:14983) is a protein-coding gene on chromosome 11q12.1, encoding E3 ubiquitin-protein ligase ZFP91 (Q96JP5). DNA-binding transcription factor.

The protein encoded by this gene is a member of the zinc finger family of proteins. The gene product contains C2H2-type domains, which are the classical zinc finger domains found in numerous nucleic acid-binding proteins. This protein functions as a regulator of the non-canonical NF-kappaB pathway in lymphotoxin-beta receptor signaling. Alternative splicing results in multiple transcript variants. A read-through transcript variant composed of ZFP91 and the downstream CNTF gene sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. A ZFP91-related pseudogene has also been identified on chromosome 2.

Source: NCBI Gene 80829 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_053023

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14983
Approved symbol	ZFP91
Name	ZFP91 zinc finger protein, atypical E3 ubiquitin ligase
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	PZF, ZNF757
Ensembl gene	ENSG00000186660
Ensembl biotype	protein_coding
OMIM	619289
Entrez	80829

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000316059, ENST00000870366, ENST00000870367, ENST00000870368, ENST00000870369

RefSeq mRNA: 2 — MANE Select: NM_053023 NM_001197051, NM_053023

CCDS: CCDS31553

Canonical transcript exons

ENST00000316059 — 11 exons

Exon	Start	End
ENSE00001254942	58617196	58621550
ENSE00001933324	58579063	58579622
ENSE00003509984	58614229	58614343
ENSE00003510427	58612762	58612840
ENSE00003518661	58610298	58610334
ENSE00003524841	58610950	58611054
ENSE00003538562	58611604	58611738
ENSE00003539689	58609830	58610039
ENSE00003564273	58616716	58616815
ENSE00003612342	58612278	58612328
ENSE00003630402	58584856	58584884

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.1562 / max 86.1572, expressed in 1645 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114353	9.8930	1785
114351	3.4994	1393
114354	1.6567	1082
114352	1.2455	792

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	98.72	gold quality
ileal mucosa	UBERON:0000331	98.45	gold quality
left ventricle myocardium	UBERON:0006566	97.81	gold quality
deltoid	UBERON:0001476	97.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.87	gold quality
cerebellar vermis	UBERON:0004720	96.73	gold quality
oviduct epithelium	UBERON:0004804	96.03	gold quality
upper arm skin	UBERON:0004263	96.00	gold quality
sperm	CL:0000019	95.88	gold quality
adult organism	UBERON:0007023	95.59	gold quality
quadriceps femoris	UBERON:0001377	95.57	gold quality
myocardium	UBERON:0002349	95.53	gold quality
cartilage tissue	UBERON:0002418	95.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.34	gold quality
biceps brachii	UBERON:0001507	95.30	gold quality
skeletal muscle tissue	UBERON:0001134	95.13	gold quality
vastus lateralis	UBERON:0001379	95.13	gold quality
epithelial cell of pancreas	CL:0000083	94.90	gold quality
muscle tissue	UBERON:0002385	94.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.57	gold quality
left testis	UBERON:0004533	94.25	gold quality
right testis	UBERON:0004534	94.05	gold quality
calcaneal tendon	UBERON:0003701	93.61	gold quality
heart right ventricle	UBERON:0002080	93.58	gold quality
testis	UBERON:0000473	93.55	gold quality
skeletal muscle organ	UBERON:0014892	93.36	gold quality
upper leg skin	UBERON:0004262	93.24	gold quality
kidney epithelium	UBERON:0004819	93.05	gold quality
skin of hip	UBERON:0001554	93.00	gold quality
islet of Langerhans	UBERON:0000006	92.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SOX10

miRNA regulators (miRDB)

265 targeting ZFP91, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
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-371B-5P	99.99	75.34	4759

Literature-anchored findings (GeneRIF, showing 18)

• likely to play an important role in cell proliferation and/or anti-apoptosis, and may serve as a molecular marker for AML (PMID:12738986)
• An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-kappaB-inducing kinase via Lys63-linked ubiquitination. (PMID:20682767)
• These data clearly indicate that ZFP91 is a key regulator in LIGHT-induced activation of non-canonical NF-kappaB pathway in LTbetaR signaling. (PMID:20804734)
• hHgher protein levels of ZFP91 in all cancer cell lines. (PMID:24272675)
• Data show that NF-kappaB/p65 is required for the binding of zinc finger protein 91 (ZFP91) to the HIF-1alpha promoter and for the transcriptional activation of HIF-1alpha gene mediated by ZFP91. (PMID:27144516)
• ZFP91 is overexpressed in prostate cancer. (PMID:27975057)
• lenalidomide induces the ubiquitination and degradation of ZFP91 (PMID:28530236)
• our findings indicated that miR-188-5p serves as a tumor suppressor in human gastric cancer (GC)by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment (PMID:29471891)
• research describes a mechanism by which ZFP91 promotes production of IL-1beta under physiological conditions and suggests that ZFP91 may be a promising therapeutic target for intervention in inflammatory, infectious and autoimmune-related diseases (PMID:30182366)
• The ubiquitinase ZFP91 promotes tumor cell survival and confers chemoresistance through FOXA1 destabilization. (PMID:31046116)
• Roles of miR-640 and Zinc Finger Protein 91 (ZFP91) in Angiopoietin-1-Induced In Vitro Angiogenesis. (PMID:32630670)
• E3 ligase ZFP91 inhibits Hepatocellular Carcinoma Metabolism Reprogramming by regulating PKM splicing. (PMID:32754263)
• MicroRNA1885p inhibits the progression of breast cancer by targeting zinc finger protein 91. (PMID:32945499)
• Zinc finger protein 91 accelerates tumour progression by activating beta-catenin signalling in pancreatic cancer. (PMID:33755268)
• ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells. (PMID:34403361)
• Overcoming IMiD resistance in T-cell lymphomas through potent degradation of ZFP91 and IKZF1. (PMID:34936696)
• Zinc finger protein 91 mediates necroptosis by initiating RIPK1-RIPK3-MLKL signal transduction in response to TNF receptor 1 ligation. (PMID:34942311)
• Atypical E3 ligase ZFP91 promotes small-molecule-induced E2F2 transcription factor degradation for cancer therapy. (PMID:36375317)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf692	ENSDARG00000078434
danio_rerio	zfp91	ENSDARG00000079631
danio_rerio	im:7147486	ENSDARG00000086626
mus_musculus	Zfp91	ENSMUSG00000024695
rattus_norvegicus	Zfp91	ENSRNOG00000012524

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

E3 ubiquitin-protein ligase ZFP91 — Q96JP5 (reviewed: Q96JP5)

Alternative names: RING-type E3 ubiquitin transferase ZFP91, Zinc finger protein 757, Zinc finger protein 91 homolog

All UniProt accessions (1): Q96JP5

UniProt curated annotations — full annotation on UniProt →

Function. DNA-binding transcription factor. Also acts as an atypical E3 ubiquitin-protein ligase that mediates ‘Lys-63’-linked ubiquitination of MAP3K14/NIK, leading to stabilize and activate MAP3K14/NIK. It thereby acts as an activator of the non-canonical NF-kappa-B2/NFKB2 pathway. May also play an important role in cell proliferation and/or anti-apoptosis.

Subunit / interactions. Interacts with Zincore complex components QRICH1 and SEPHS1; stabilizing ZFP91 at DNA-binding sites across the genome.

Subcellular location. Nucleus.

Tissue specificity. Expressed ubiquitously, particularly at high level in testis. Isoform 2 is testis specific.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. In contrast to other E3 ubiquitin-protein ligase, does not contain any domain (RING-type zinc finger or HECT domain) known to mediate E3 ligase activity.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96JP5-1	1	yes
Q96JP5-2	2

RefSeq proteins (2): NP_001183980, NP_444251* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051061

Pfam: PF00096

UniProt features (58 total): binding site 20, compositionally biased region 10, zinc finger region 5, strand 4, helix 4, modified residue 2, splice variant 2, sequence variant 2, mutagenesis site 2, sequence conflict 2, region of interest 2, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9HJU	ELECTRON MICROSCOPY	3.16
9HJT	ELECTRON MICROSCOPY	3.26
2M9A	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JP5-F1	52.06	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (20): 313; 318; 331; 336; 344; 349; 362; 366; 374; 377; 390; 394 …

Post-translational modifications (2): 83, 103

Mutagenesis-validated functional residues (2):

Position	Phenotype
344	abolishes ubiquitination of map3k14/nik; when associated with a-349.
349	abolishes ubiquitination of map3k14/nik; when associated with a-344.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 271 (showing top): GGGACCA_MIR133A_MIR133B, TGGTGCT_MIR29A_MIR29B_MIR29C, MYOGENIN_Q6, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCACTT_MIR519C_MIR519B_MIR519A, GCANCTGNY_MYOD_Q6, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ACTIVATION_OF_NF_KAPPAB_INDUCING_KINASE_ACTIVITY, GCAAGGA_MIR502, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, USF_C

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), activation of NF-kappaB-inducing kinase activity (GO:0007250), positive regulation of transcription by RNA polymerase II (GO:0045944), protein K63-linked ubiquitination (GO:0070534), protein ubiquitination (GO:0016567), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (7): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
regulation of metabolic process	2
nuclear lumen	2
regulation of DNA-templated transcription	1
activation of protein kinase activity	1
non-canonical NF-kappaB signal transduction	1
positive regulation of DNA-templated transcription	1
protein polyubiquitination	1
protein modification by small protein conjugation	1
macromolecule metabolic process	1
primary metabolic process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFP91	CRBN	Q96SW2	718
ZFP91	GSPT1	P15170	597
ZFP91	PAK1IP1	Q9NWT1	543
ZFP91	RNF166	Q96A37	540
ZFP91	FBXW2	Q9UKT8	528
ZFP91	ZNF827	Q17R98	524
ZFP91	DDB1	Q16531	518
ZFP91	HTATSF1	O43719	463
ZFP91	CSNK1A1	P48729	447
ZFP91	CDC40	O60508	434
ZFP91	H7C0V5	H7C0V5	430
ZFP91	RBX1	P62877	425
ZFP91	K7EP71	K7EP71	423
ZFP91	SACK1C	Q9BQN1	422
ZFP91	AP3D1	O14617	418

IntAct

125 interactions, top by confidence:

A	B	Type	Score
CHCHD10	CLPX	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
ZFP91	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	AGR2	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	TP53BP2	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	ZNF526	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	PICK1	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	CEP70	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	POU6F2	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	ZFP41	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	FAM9A	psi-mi:“MI:0915”(physical association)	0.560
tat	PPM1G	psi-mi:“MI:0914”(association)	0.560
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
CLEC3A	ZZEF1	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ADARB1	SPTY2D1	psi-mi:“MI:0914”(association)	0.530
AURKAIP1	NRDC	psi-mi:“MI:0914”(association)	0.480
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
PAEP	ESYT2	psi-mi:“MI:0914”(association)	0.350
Set	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (200): ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Proximity Label-MS), ZFP91 (Biochemical Activity), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS), ZFP91 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ4, A4IHR5, A6H7J1, A7UKY7, D4AE48, E9Q9M8, O15209, O35615, O75081, O95785, P03966, P04198, P39881, P49796, P52746, Q01101, Q1LY51, Q29RS4, Q32KV8, Q4KLY2, Q505G8, Q5T6C5, Q5TJE2, Q61976, Q62511, Q63379, Q63ZV0, Q6AY75, Q6NUJ5, Q6NV74, Q6P0F9, Q7T3H2, Q8BG80, Q8CDC7, Q8CE64, Q8IX07, Q8N554, Q8R4U1, Q96C00, Q96JP5

Diamond homologs: A0JNJ4, F6WEQ6, Q3U381, Q62511, Q96JP5, Q9BU19, A1C6L9, A1DH89, A2QCJ9, B0XSK6, B8NGC8, G4N3L5, K9GKQ6, O14335, O74252, O94166, P08047, P0CG40, P10069, P13574, P27705, P43079, P46099, P58334, P78871, Q01981, Q05620, Q08400, Q0VA40, Q13351, Q14V87, Q19A40, Q22678, Q24266, Q3SY56, Q4WRE4, Q4X0Z3, Q5AMH6, Q5XGT8, Q64HY3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ZFP91	up-regulates	MAP3K14	ubiquitination
ZFP91	“down-regulates quantity”	HNRNPF	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Eukaryotic Translation Initiation	8	27.1×	8e-09
Cap-dependent Translation Initiation	8	27.1×	8e-09
SARS-CoV-1 modulates host translation machinery	8	27.1×	8e-09
Nonsense-Mediated Decay (NMD)	10	25.6×	1e-10
Eukaryotic Translation Elongation	8	24.5×	2e-08
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	8	23.9×	2e-08
Influenza Viral RNA Transcription and Replication	9	21.3×	7e-09
Peptide chain elongation	15	20.9×	3e-14

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	16	24.1×	3e-15
ribosomal small subunit biogenesis	8	14.8×	2e-05
translation	14	11.7×	5e-09
negative regulation of translation	6	9.6×	5e-03
nucleosome assembly	7	8.0×	5e-03
mRNA splicing, via spliceosome	8	6.0×	6e-03
RNA splicing	8	5.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2011 predictions. Top by Δscore:

Variant	Effect	Δscore
11:58579623:G:GG	donor_gain	1.0000
11:58583582:G:GG	donor_gain	1.0000
11:58583628:G:GG	donor_gain	1.0000
11:58609828:A:AG	acceptor_gain	1.0000
11:58609829:G:GT	acceptor_gain	1.0000
11:58609829:GA:G	acceptor_gain	1.0000
11:58609829:GAT:G	acceptor_gain	1.0000
11:58609877:G:GT	donor_gain	1.0000
11:58609976:TCC:T	donor_gain	1.0000
11:58610008:G:GG	donor_gain	1.0000
11:58610035:TTATG:T	donor_loss	1.0000
11:58610036:TATGG:T	donor_loss	1.0000
11:58610037:ATG:A	donor_loss	1.0000
11:58610039:GGTAC:G	donor_loss	1.0000
11:58610040:G:T	donor_loss	1.0000
11:58610041:T:A	donor_loss	1.0000
11:58610293:TCTAG:T	acceptor_loss	1.0000
11:58610294:CTAG:C	acceptor_loss	1.0000
11:58610295:TAG:T	acceptor_loss	1.0000
11:58610295:TAGA:T	acceptor_loss	1.0000
11:58610296:A:AG	acceptor_gain	1.0000
11:58610296:AGA:A	acceptor_loss	1.0000
11:58610297:G:GA	acceptor_gain	1.0000
11:58610297:G:GG	acceptor_gain	1.0000
11:58610297:GAT:G	acceptor_gain	1.0000
11:58610331:TTAGG:T	donor_loss	1.0000
11:58610332:TAGGT:T	donor_loss	1.0000
11:58610333:AG:A	donor_loss	1.0000
11:58610334:GGT:G	donor_loss	1.0000
11:58610335:G:GA	donor_loss	1.0000

AlphaMissense

3719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:58612790:T:A	C313S	1.000
11:58612790:T:C	C313R	1.000
11:58612791:G:A	C313Y	1.000
11:58612791:G:C	C313S	1.000
11:58612792:T:G	C313W	1.000
11:58612805:T:A	C318S	1.000
11:58612805:T:C	C318R	1.000
11:58612806:G:C	C318S	1.000
11:58614271:T:A	C344S	1.000
11:58614271:T:C	C344R	1.000
11:58614272:G:C	C344S	1.000
11:58614273:T:G	C344W	1.000
11:58614286:T:C	C349R	1.000
11:58614287:G:A	C349Y	1.000
11:58614288:T:G	C349W	1.000
11:58614298:T:C	F353L	1.000
11:58614299:T:C	F353S	1.000
11:58614300:C:A	F353L	1.000
11:58614300:C:G	F353L	1.000
11:58614317:T:C	L359P	1.000
11:58616733:T:C	C374R	1.000
11:58616734:G:A	C374Y	1.000
11:58616735:T:G	C374W	1.000
11:58616742:T:C	C377R	1.000
11:58616743:G:A	C377Y	1.000
11:58616744:T:G	C377W	1.000
11:58616754:T:A	F381I	1.000
11:58616754:T:C	F381L	1.000
11:58616755:T:C	F381S	1.000
11:58616756:C:A	F381L	1.000

dbSNP variants (sampled 300 via entrez): RS1000069415 (11:58622037 G>A), RS1000128669 (11:58599161 T>A,C), RS1000148222 (11:58582084 G>C), RS1000230816 (11:58605444 G>A), RS1000281474 (11:58605172 A>G), RS1000293461 (11:58598650 T>G), RS1000321348 (11:58587561 G>T), RS1000345310 (11:58598911 A>C), RS1000365042 (11:58617895 C>T), RS1000394194 (11:58599300 T>C,G), RS1000620672 (11:58603702 A>G), RS1000621678 (11:58605368 A>G,T), RS1000826184 (11:58577592 G>A,T), RS1000835149 (11:58615862 T>A), RS1000867859 (11:58578286 G>A,T)

Disease associations

OMIM: gene MIM:619289 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004133_47	Ulcerative colitis	9.000000e-06
GCST007267_74	Systolic blood pressure	4.000000e-11
GCST007565_6	Morning person	3.000000e-15
GCST007576_33	Chronotype	3.000000e-15
GCST007929_44	Medication use (calcium channel blockers)	6.000000e-10
GCST010242_163	HDL cholesterol levels	1.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523709 (PROTEIN-PROTEIN INTERACTION), CHEMBL4739701 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.33	Kd	462	nM	BUFALIN

PubChem BioAssay actives

1 with measured affinity, of 17 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[(3S,5R,8R,9S,10S,13R,14S,17R)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pyran-2-one	2067035: Binding affinity to ZFP91 (unknown origin) assessed as dissociation constant	kd	0.4620	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	decreases expression, affects cotreatment	1
TAK-243	increases sumoylation	1
trichostatin A	affects expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone	increases reaction, affects cotreatment, increases phosphorylation, affects binding	1
pomalidomide	decreases expression, increases degradation	1
abrine	increases expression	1
SM 164	affects cotreatment, increases phosphorylation	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Sunitinib	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Succimer	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Indomethacin	decreases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Magnetite Nanoparticles	affects cotreatment, increases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4313026	Binding	Induction of CRBN-mediated ZFP91 degradation in human U251 cells at 500 nM after 4 hrs by TMT Mass spectrometry based proteomic analysis	Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders. — J Med Chem

Clinical trials (associated diseases)

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