ZBTB35

Summary

ZBTB35 (zinc finger and BTB domain containing 35, HGNC:12915) is a protein-coding gene on chromosome 5p12, encoding Zinc finger protein 131 (P52739). Plays a role during development and organogenesis as well as in the function of the adult central nervous system. It is a common-essential gene (DepMap: required in 92.7% of cancer cell lines).

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Located in intermediate filament cytoskeleton and nucleoplasm.

Source: NCBI Gene 7690 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 53 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 92.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001330707

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12915
Approved symbol	ZBTB35
Name	zinc finger and BTB domain containing 35
Location	5p12
Locus type	gene with protein product
Status	Approved
Aliases	ZBTB35
Ensembl gene	ENSG00000172262
Ensembl biotype	protein_coding
OMIM	604073
Entrez	7690

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 24 protein_coding, 4 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000306938, ENST00000499046, ENST00000502623, ENST00000503599, ENST00000504359, ENST00000505606, ENST00000507218, ENST00000507231, ENST00000507393, ENST00000508259, ENST00000508795, ENST00000509156, ENST00000509341, ENST00000509634, ENST00000509931, ENST00000510026, ENST00000510037, ENST00000511736, ENST00000514169, ENST00000515326, ENST00000682664, ENST00000874854, ENST00000874855, ENST00000874856, ENST00000874857, ENST00000874858, ENST00000874859, ENST00000874860, ENST00000933525, ENST00000933526, ENST00000933527, ENST00000962179, ENST00000962180, ENST00000962181, ENST00000962182

RefSeq mRNA: 17 — MANE Select: NM_001330707 NM_001297548, NM_001330704, NM_001330705, NM_001330706, NM_001330707, NM_001330708, NM_001330709, NM_001330710, NM_001330711, NM_001330712, NM_001330713, NM_001330714, NM_001330715, NM_001330716, NM_001330717, NM_001388319, NM_003432

CCDS: CCDS43313, CCDS78005

Canonical transcript exons

ENST00000682664 — 7 exons

Exon	Start	End
ENSE00001489230	43139165	43139309
ENSE00003492608	43173318	43173448
ENSE00003561516	43161249	43161931
ENSE00003581909	43122039	43122177
ENSE00003671404	43123209	43123310
ENSE00003920728	43174447	43176322
ENSE00003921715	43120914	43121123

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8416 / max 153.9140, expressed in 1797 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56325	5.0151	1494
56329	2.7254	1223
56327	2.1488	1245
56328	2.0174	1183
56319	1.4428	712
56323	0.8933	581
56322	0.7129	482
56330	0.5086	218
56326	0.3773	146

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.42	gold quality
oocyte	CL:0000023	98.04	gold quality
endothelial cell	CL:0000115	95.47	gold quality
cortical plate	UBERON:0005343	95.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.17	gold quality
ganglionic eminence	UBERON:0004023	95.15	gold quality
cervix squamous epithelium	UBERON:0006922	94.88	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.21	gold quality
sperm	CL:0000019	93.90	gold quality
ventricular zone	UBERON:0003053	93.90	gold quality
calcaneal tendon	UBERON:0003701	93.60	gold quality
right testis	UBERON:0004534	93.12	gold quality
left testis	UBERON:0004533	92.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.78	gold quality
visceral pleura	UBERON:0002401	92.59	gold quality
testis	UBERON:0000473	92.58	gold quality
primary visual cortex	UBERON:0002436	92.49	gold quality
male germ cell	CL:0000015	92.48	gold quality
cerebellar hemisphere	UBERON:0002245	92.35	gold quality
gingival epithelium	UBERON:0001949	92.28	gold quality
cerebellar cortex	UBERON:0002129	92.28	gold quality
parietal pleura	UBERON:0002400	91.70	gold quality
colonic epithelium	UBERON:0000397	91.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.56	gold quality
amniotic fluid	UBERON:0000173	91.53	gold quality
pleura	UBERON:0000977	91.38	gold quality
cerebellum	UBERON:0002037	91.35	gold quality
squamous epithelium	UBERON:0006914	91.01	gold quality
endocervix	UBERON:0000458	90.90	gold quality
lymph node	UBERON:0000029	90.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.45

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2546.1	ZNF131	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

119 targeting ZBTB35, 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-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-124-3P	99.89	73.74	3043

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 92.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• The mechanism of Znf131 nuclear localization, is reported. (PMID:17306895)
• Interaction between ZNF131 and ERalpha interrupts or prevents ERalpha binding to the estrogen response element. ZNF131 also suppresses the expression of TFF1. (PMID:18847501)
• SUMOylation is a novel regulator of ZNF131 action in estrogen signaling and breast cancer cell proliferation. (PMID:22467880)
• these data suggest that ZNF131 inhibits estrogen signaling by acting as an ERalpha-co-repressor. (PMID:23159625)
• UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3 ligase for zinc finger protein 131 (PMID:23404503)
• identify a novel substoichiometric interactor of the complex, transcription factor ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. (PMID:26841866)
• Our results suggest that GSCs differentially rely on ZNF131-dependent expression of HAUS5 as well as the Augmin/HAUS complex activity to maintain the integrity of centrosome function and viability. (PMID:28596487)
• Knockdown circZNF131 Inhibits Cell Progression and Glycolysis in Gastric Cancer Through miR-186-5p/PFKFB2 Axis. (PMID:35059934)
• The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by repressing pro-differentiation genes. (PMID:35294876)
• YAP1-activated ZNF131 promotes hepatocellular carcinoma cell proliferation through transcriptional regulation of PAIP1. (PMID:38341068)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf131	ENSDARG00000068400
mus_musculus	Zfp131	ENSMUSG00000094870
rattus_norvegicus	Zfp131	ENSRNOG00000015925
drosophila_melanogaster	hb	FBGN0001180
drosophila_melanogaster	CG12391	FBGN0033581
caenorhabditis_elegans		WBGENE00001824
caenorhabditis_elegans		WBGENE00012385

Paralogs (29): ZNF446 (ENSG00000083838), REST (ENSG00000084093), ZNF174 (ENSG00000103343), OVOL3 (ENSG00000105261), PLAGL1 (ENSG00000118495), ZSCAN18 (ENSG00000121413), ZNF576 (ENSG00000124444), OVOL2 (ENSG00000125850), PLAGL2 (ENSG00000126003), ZSCAN5A (ENSG00000131848), ZSCAN29 (ENSG00000140265), ZSCAN32 (ENSG00000140987), ZSCAN1 (ENSG00000152467), ZNF18 (ENSG00000154957), ZKSCAN2 (ENSG00000155592), ZNF496 (ENSG00000162714), ZNF202 (ENSG00000166261), ZNF641 (ENSG00000167528), ZNF444 (ENSG00000167685), SCAND1 (ENSG00000171222), ZNF274 (ENSG00000171606), OVOL1 (ENSG00000172818), ZNF518A (ENSG00000177853), ZNF518B (ENSG00000178163), PLAG1 (ENSG00000181690), ZSCAN5B (ENSG00000197213), ZNF770 (ENSG00000198146), PEG3 (ENSG00000198300), ZSCAN5C (ENSG00000204532)

Protein

Protein identifiers

Zinc finger protein 131 — P52739 (reviewed: P52739)

All UniProt accessions (10): D6R9I2, D6RAT8, D6RBK1, D6RD61, D6RE06, D6RFI6, D6RJ09, D6RJH2, P52739, H0Y974

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role during development and organogenesis as well as in the function of the adult central nervous system. May be involved in transcriptional regulation as a repressor of ESR1/ER-alpha signaling.

Subcellular location. Nucleus.

Tissue specificity. Predominant expression is found in different brain areas such as the occipital and temporal lobe, the nucleus caudatus, hippocampus, and the cerebellum as well as in testis and thymus.

Post-translational modifications. Monosumoylated at Lys-601 by CBX4 and UHRF2. Sumoylation may potentiate ZNF131 inhibition of estrogen signaling. Sumoylation does not interfere with ubiquitination. Ubiquitinated.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P52739-1	1	yes
P52739-2	2

RefSeq proteins (17): NP_001284477, NP_001317633, NP_001317634, NP_001317635, NP_001317636, NP_001317637, NP_001317638, NP_001317639, NP_001317640, NP_001317641, NP_001317642, NP_001317643, NP_001317644, NP_001317645, NP_001317646, NP_001375248, NP_003423 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00651, PF12874

UniProt features (25 total): mutagenesis site 6, zinc finger region 6, cross-link 3, sequence conflict 3, short sequence motif 2, chain 1, domain 1, compositionally biased region 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52739-F1	53.58	0.05

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 (3): 289, 295, 601

Mutagenesis-validated functional residues (6):

Position	Phenotype
242	no effect on sumoylation; when associated with r-281 and r-289.
281	no effect on sumoylation; when associated with r-242 and r-281.
289	no effect on sumoylation; when associated with r-242 and r-281.
477	small loss of sumoylation. complete loss of cbx4 sumoylation; when associated with r-601 and r-610.
601	significant loss of sumoylation. complete loss of cbx4 sumoylation; when associated with r-477 and r-610.
610	no effect on sumoylation. complete loss of cbx4 sumoylation; when associated with r-477 and r-601.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3899300	SUMOylation of transcription cofactors

MSigDB gene sets: 249 (showing top): MORF_DNMT1, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MORF_CDK2, TATTATA_MIR374, BROWNE_HCMV_INFECTION_16HR_UP, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CYTOKINE_PRODUCTION, MORF_RFC4, MORF_PRKDC, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MORF_PAPSS1

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), intermediate filament cytoskeleton (GO:0045111), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
immune system process	1
regulation of biological process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	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
binding	1
DNA binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoskeleton	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB35	EMSY	Q7Z589	699
ZBTB35	HAUS5	O94927	504
ZBTB35	SIN3B	O75182	485
ZBTB35	CCDC152	Q4G0S7	456
ZBTB35	HAUS3	Q68CZ6	447
ZBTB35	OPRD1	P41143	445
ZBTB35	HAUS7	Q99871	440
ZBTB35	NIM1K	Q8IY84	419
ZBTB35	SIM1	P81133	416
ZBTB35	GABRA2	P47869	410
ZBTB35	PLEKHG1	Q9ULL1	389
ZBTB35	ZNF91	Q05481	384
ZBTB35	HAUS8	Q9BT25	377
ZBTB35	PCDHB6	Q9Y5E3	376
ZBTB35	PCDHB15	Q9Y5E8	375
ZBTB35	PCDHB10	Q9UN67	375

IntAct

52 interactions, top by confidence:

A	B	Type	Score
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
ZBTB18	HSPA8	psi-mi:“MI:0914”(association)	0.640
ZNF131	FHL2	psi-mi:“MI:0915”(physical association)	0.550
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
MRM3	NDUFS6	psi-mi:“MI:0914”(association)	0.530
FHL5	ZMYM6	psi-mi:“MI:0914”(association)	0.530
ZNF131	GNB3	psi-mi:“MI:0915”(physical association)	0.400
ZNF131	E7	psi-mi:“MI:0915”(physical association)	0.370
HSPB1	ZNF131	psi-mi:“MI:0915”(physical association)	0.370
ZNF131	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
Nrip3	ILVBL	psi-mi:“MI:0914”(association)	0.350
PRKCD	DHX16	psi-mi:“MI:0914”(association)	0.350
CDK8	CCNC	psi-mi:“MI:0914”(association)	0.350
CREB1	NFIX	psi-mi:“MI:0914”(association)	0.350
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
MBIP	CIBAR1	psi-mi:“MI:0914”(association)	0.350
ZBTB3	VWA8	psi-mi:“MI:0914”(association)	0.350
GDF11	TSPY2	psi-mi:“MI:0914”(association)	0.350
ZBTB18	ZBTB42	psi-mi:“MI:0914”(association)	0.350
BACH2	ENC1	psi-mi:“MI:0914”(association)	0.350
HINT1	OGA	psi-mi:“MI:0914”(association)	0.350
PHF1	DNAJC13	psi-mi:“MI:0914”(association)	0.350
PDE12	LONP1	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
ZBTB3	AHCYL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): ZNF131 (Two-hybrid), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Two-hybrid), ZNF131 (Two-hybrid), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), ZNF131 (Affinity Capture-MS)

ESM2 similar proteins: A1L1J6, A2ANX9, A7Y7X5, E9Q8T2, G5E8B9, O15060, O43167, O43829, O62836, O95625, P08048, P0C6P6, P10925, P17010, P17012, P20662, P52739, Q01611, Q08376, Q0VCB0, Q2FAY8, Q3TTC2, Q4V8R6, Q52V16, Q5DU09, Q5PPG4, Q5R5M1, Q5R5N5, Q5RAU9, Q5SVQ8, Q6B4Z5, Q6GNP2, Q6INV8, Q7TS63, Q7ZVR6, Q80V63, Q80X44, Q811F1, Q8K3J5, Q92010

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
Epigenetic regulation by WDR5-containing histone modifying complexes	5	17.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1157 predictions. Top by Δscore:

Variant	Effect	Δscore
5:43121569:G:GG	donor_gain	1.0000
5:43122037:A:AG	acceptor_gain	1.0000
5:43122038:G:GG	acceptor_gain	1.0000
5:43122038:GA:G	acceptor_gain	1.0000
5:43122038:GAGC:G	acceptor_gain	1.0000
5:43122038:GAGCA:G	acceptor_gain	1.0000
5:43122144:G:GT	donor_gain	1.0000
5:43122174:GACG:G	donor_gain	1.0000
5:43122178:GT:G	donor_loss	1.0000
5:43122178:GTGG:G	donor_gain	1.0000
5:43122179:T:G	donor_loss	1.0000
5:43123198:A:AG	acceptor_gain	1.0000
5:43123203:A:AG	acceptor_gain	1.0000
5:43123204:C:G	acceptor_gain	1.0000
5:43123205:CTAG:C	acceptor_loss	1.0000
5:43123206:TAGG:T	acceptor_loss	1.0000
5:43123207:A:AG	acceptor_gain	1.0000
5:43123207:A:G	acceptor_loss	1.0000
5:43123207:AG:A	acceptor_gain	1.0000
5:43123208:G:GG	acceptor_gain	1.0000
5:43123208:GG:G	acceptor_gain	1.0000
5:43123208:GGAC:G	acceptor_gain	1.0000
5:43123208:GGACA:G	acceptor_gain	1.0000
5:43123308:AAGG:A	donor_loss	1.0000
5:43123310:GGT:G	donor_loss	1.0000
5:43123311:G:GA	donor_loss	1.0000
5:43123312:T:A	donor_loss	1.0000
5:43139159:TTACA:T	acceptor_loss	1.0000
5:43139163:A:AG	acceptor_gain	1.0000
5:43139164:G:GG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004770 (5:43155349 G>A), RS1000092881 (5:43166364 C>T), RS1000117099 (5:43146859 T>A), RS1000118960 (5:43124077 T>C), RS1000143705 (5:43174495 G>A), RS1000194851 (5:43166846 G>A), RS1000207002 (5:43158339 G>A,T), RS1000222429 (5:43128092 T>A), RS1000248670 (5:43166635 A>G), RS1000269959 (5:43121843 C>A,T), RS1000333242 (5:43123107 A>G), RS1000360560 (5:43163570 C>A,G,T), RS1000386674 (5:43121704 C>T), RS1000444890 (5:43161158 A>G), RS1000450856 (5:43127065 A>G,T)

Disease associations

OMIM: gene MIM:604073 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002541_12	Menarche (age at onset)	4.000000e-09
GCST002783_467	Body mass index	9.000000e-06
GCST90002391_31	Mean corpuscular hemoglobin concentration	4.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5069380 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
Benzo(a)pyrene	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
deguelin	increases expression	1
entinostat	decreases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Vitamin E	decreases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5059513	Binding	Proteomics fold change data (SUDHL4 cells, 1h)	Data for DCP probe CCT369260

Clinical trials (associated diseases)

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