POLR1H

Summary

POLR1H (RNA polymerase I subunit H, HGNC:13182) is a protein-coding gene on chromosome 6p22.1, encoding DNA-directed RNA polymerase I subunit RPA12 (Q9P1U0). Core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. It is a selective cancer dependency (DepMap: 84.8% of cell lines).

This gene encodes a DNA-directed RNA polymerase I subunit. The encoded protein contains two potential zinc-binding motifs and may play a role in regulation of cell proliferation. The encoded protein may be involved in cancer and human immunodeficiency virus progression. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 30834 — RefSeq curated summary.

At a glance

• GWAS associations: 32
• Clinical variants (ClinVar): 19 total
• Cancer dependency (DepMap): dependent in 84.8% of screened cell lines
• MANE Select transcript: NM_170783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13182
Approved symbol	POLR1H
Name	RNA polymerase I subunit H
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	hZR14, HTEX-6, tctex-6, RPA12, A12.2
Ensembl gene	ENSG00000066379
Ensembl biotype	protein_coding
OMIM	607525
Entrez	30834

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000332435, ENST00000359374, ENST00000376782, ENST00000376785, ENST00000463141, ENST00000471008, ENST00000932219

RefSeq mRNA: 4 — MANE Select: NM_170783 NM_001278785, NM_001278786, NM_014596, NM_170783

CCDS: CCDS4670

Canonical transcript exons

ENST00000332435 — 4 exons

Exon	Start	End
ENSE00001706051	30061917	30062017
ENSE00001914162	30061265	30061669
ENSE00003548268	30062224	30062333
ENSE00003843623	30064673	30064907

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 93.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.2360 / max 184.6656, expressed in 1805 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66690	10.0636	1756
66689	7.7087	1750
66691	6.9866	1652
66692	1.0039	682
66693	0.3308	161
66694	0.1424	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.51	gold quality
mucosa of transverse colon	UBERON:0004991	92.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.65	gold quality
lymph node	UBERON:0000029	91.63	gold quality
blood	UBERON:0000178	90.74	gold quality
leukocyte	CL:0000738	90.48	gold quality
lower esophagus mucosa	UBERON:0035834	90.48	gold quality
vermiform appendix	UBERON:0001154	90.33	gold quality
monocyte	CL:0000576	90.21	gold quality
rectum	UBERON:0001052	90.20	gold quality
spleen	UBERON:0002106	90.18	gold quality
body of pancreas	UBERON:0001150	89.77	gold quality
right adrenal gland	UBERON:0001233	89.59	gold quality
apex of heart	UBERON:0002098	89.56	gold quality
body of stomach	UBERON:0001161	89.47	gold quality
esophagus mucosa	UBERON:0002469	89.34	gold quality
left testis	UBERON:0004533	89.32	gold quality
pancreas	UBERON:0001264	89.18	gold quality
left adrenal gland cortex	UBERON:0035825	89.10	gold quality
left adrenal gland	UBERON:0001234	89.07	gold quality
fundus of stomach	UBERON:0001160	89.05	gold quality
duodenum	UBERON:0002114	89.01	gold quality
omental fat pad	UBERON:0010414	88.98	gold quality
testis	UBERON:0000473	88.95	gold quality
right adrenal gland cortex	UBERON:0035827	88.89	gold quality
right testis	UBERON:0004534	88.86	gold quality
descending thoracic aorta	UBERON:0002345	88.71	gold quality
left ovary	UBERON:0002119	88.67	gold quality
fallopian tube	UBERON:0003889	88.60	gold quality
islet of Langerhans	UBERON:0000006	88.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ABCB1	Activation
BCL2	Activation

miRNA regulators (miRDB)

19 targeting POLR1H, 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-651-3P	99.94	73.48	5177
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-3130-5P	98.14	66.00	711
HSA-MIR-4482-5P	97.53	65.68	598
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-193A-5P	95.70	65.33	613

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 24)

• ZNRD1 gene displays high expression in VCR resistant gastric cancer cells. (PMID:12795835)
• overexpression of ZNRD1 could promote multidrug-resistant phenotype of gastric cancer cells through upregulation of P-glycoprotein (PMID:14726695)
• This study clearly demonstrates that ZNRD1 may play an important role in the control of human gastric cancer development by regulating cell proliferation. (PMID:15358150)
• ZNRD1 may play an important role in the regulation of gastric carcinogenesis and could be used as a new target in treatment of stomach cancer (PMID:15662122)
• ZNRD1 significantly inhibits the in vitro and in vivo growth of human gastric cancer cell line MKN28 by targeting cell cycle-related genes and reducing tumor angiogenesis. (PMID:17389617)
• The up-regulation of ZNRD1 significantly inhibited the drug sensitivity of gastric cancer cells over-expressing DARPP-32, indicating that ZNRD1 may be important in the DARPP-32-mediated MDR of gastric cancer (PMID:17492506)
• DARPP-32 mediates multidrug resistance of gastric cancer through regulation of P-gp and ZNRD1. (PMID:18058465)
• ZNRD1-expressing cells exhibited enhanced DNA repair capacity and overexpression could upregulate the expression of excision repair cross-complementing 1 (ERCC1) gene (PMID:18564169)
• ZNRD1 was down-regulated in esophageal cancer tissues compared to adjacent non-neoplastic tissues. (PMID:18594968)
• Data demonstrate that the influence of ZNRD1 alleles on disease progression rates are attributable to HLA-A10, help clarify the relationship between the HCP5, HLA-C and HLA-B*57 alleles, and reaffirm a critical role of HLA-B*57 alleles in HIV disease. (PMID:18982067)
• siRNA-based functional analysis showed that ZNRD1 down-regulation by siRNA or shRNA impaired HIV-1 replication at the transcription level in both lymphoid and nonlymphoid cells. (PMID:20192730)
• The results of human miRNA array and real-time PCR showed that ZNRD1 could significantly up-regulate the expression of miR-214 and down-regulate the expression of miR-296. (PMID:21080911)
• Nominal associations were found between ZNRD1 rs1150740 and risk of AERD via codominant and dominant genetic inheritance (P=.03; odds ratio, 1.14 [1.14-10.16]). (PMID:22697009)
• Variants in ZNRD1 gene predict HIV-1/AIDS disease progression in a Han Chinese population in Taiwan. (PMID:23874430)
• A miR-508-5p/ZNRD1/ABCB1 regulatory loop has a critical role in MDR in gastric cancer. (PMID:23893241)
• This study provides novel evidence that ZNRD1 polymorphism may confer host resistance to HIV-1 acquisition. (PMID:24842830)
• ZNRD1 regulatory SNPs may be susceptibility makers for risk of both chronic HBV infection and HCC. (PMID:25110835)
• The minor alleles of rs2395029, rs9264942, and rs3689068 in the HCP5 and HLA-C, and ZNRD1 genes associate with lower viral loads (VL) among antiretroviral-naive individuals and with shorter time to first VL less 51 copies/ml during anti-HIV therapy. (PMID:27083073)
• Findings suggest a tumor suppressor function for ZNRD1 gene and a tumor contributor function for long noncoding RNAs (IncRNAs) ZNRD1-AS1 in the process of carcinogenesis of lung cancer. (PMID:27166266)
• MiR-26b suppresses hepatocellular carcinoma development by negatively regulating ZNRD1 and Wnt/beta-catenin signaling. (PMID:31637871)
• ZNRD1-AS and RP11-819C21.1 long non-coding RNA changes following painful laser stimulation correlate with laser-evoked potential amplitude and habituation in healthy subjects: A pilot study. (PMID:31782860)
• ZNRD1 and Its Antisense Long Noncoding RNA ZNRD1-AS1 Are Oppositely Regulated by Cold Atmospheric Plasma in Breast Cancer Cells. (PMID:32454947)
• RNA polymerase I subunit 12 plays opposite roles in cell proliferation and migration. (PMID:33984768)
• Expression of RNA polymerase I catalytic core is influenced by RPA12. (PMID:37167337)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr1h	ENSDARG00000036070
mus_musculus	Polr1h	ENSMUSG00000036315
rattus_norvegicus	Polr1h	ENSRNOG00000000779
drosophila_melanogaster	Polr1H	FBGN0038903
caenorhabditis_elegans		WBGENE00007616

Paralogs (2): POLR2I (ENSG00000105258), POLR3K (ENSG00000161980)

Protein

Protein identifiers

DNA-directed RNA polymerase I subunit RPA12 — Q9P1U0 (reviewed: Q9P1U0)

Alternative names: DNA-directed RNA polymerase I subunit H, Zinc ribbon domain-containing protein 1

All UniProt accessions (2): Q9P1U0, Q2L6J2

UniProt curated annotations — full annotation on UniProt →

Function. Core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Can mediate Pol I proofreading of the nascent RNA transcript. Anchors into the Pol I active site to monitor transcription fidelity and cleave mis-incorporated 5’-ribonucleotides.

Subunit / interactions. Component of the RNA polymerase I (Pol I) complex consisting of 13 subunits: a ten-subunit catalytic core composed of POLR1A/RPA1, POLR1B/RPA2, POLR1C/RPAC1, POLR1D/RPAC2, POLR1H/RPA12, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5; a mobile stalk subunit POLR1F/RPA43 protruding from the core and additional subunits homologous to general transcription factors POLR1E/RPA49 and POLR1G/RPA34. Part of Pol I pre-initiation complex (PIC), in which Pol I core assembles with RRN3 and promoter-bound UTBF and SL1/TIF-IB complex.

Subcellular location. Nucleus. Nucleolus.

Domain organisation. The TFIIS-type zinc-binding beta-ribbon domain contains an acidic hairpin motif (residues Asp-106, Glu-107) that likely coordinates the nucleophilic water and magnesium to cleave the scissile phosphodiester bond and release the mis-incorporated 5’-ribonucleotides.

Similarity. Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.

RefSeq proteins (4): NP_001265714, NP_001265715, NP_055411, NP_740753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001222	Znf_TFIIS	Domain
IPR012164	Rpa12/Rpb9/Rpc10/TFS	Family
IPR019761	DNA-dir_RNA_pol-M_15_CS	Conserved_site
IPR034004	Zn_ribbon_RPA12_C	Domain

Pfam: PF01096

UniProt features (25 total): strand 9, binding site 8, zinc finger region 2, turn 2, chain 1, sequence variant 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7OB9	ELECTRON MICROSCOPY	2.7
7VBB	ELECTRON MICROSCOPY	2.81
7VBA	ELECTRON MICROSCOPY	2.89
7VBC	ELECTRON MICROSCOPY	3.01
7OBA	ELECTRON MICROSCOPY	3.1
7OBB	ELECTRON MICROSCOPY	3.3
8A43	ELECTRON MICROSCOPY	4.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P1U0-F1	80.39	0.30

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 (8): 115; 118; 20; 23; 38; 41; 87; 90

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5250941	Negative epigenetic regulation of rRNA expression
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 120 (showing top): GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_RRNA_TRANSCRIPTION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, KEGG_PURINE_METABOLISM, GOCC_RNA_POLYMERASE_COMPLEX, DANG_BOUND_BY_MYC, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_TRANSFERASE_COMPLEX, KEGG_RNA_POLYMERASE, GOCC_NUCLEOLUS

GO Biological Process (3): nucleobase-containing compound metabolic process (GO:0006139), termination of RNA polymerase I transcription (GO:0006363), DNA-templated transcription (GO:0006351)

GO Molecular Function (5): nucleic acid binding (GO:0003676), DNA-directed RNA polymerase activity (GO:0003899), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), RNA polymerase I complex (GO:0005736), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
RNA Polymerase I Promoter Clearance	2
RNA Polymerase I Transcription	2
Gene expression (Transcription)	2
Epigenetic regulation of gene expression	2
Negative epigenetic regulation of rRNA expression	1
Positive epigenetic regulation of rRNA expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA biosynthetic process	2
binding	2
nuclear lumen	2
primary metabolic process	1
DNA-templated transcription termination	1
transcription by RNA polymerase I	1
gene expression	1
5’-3’ RNA polymerase activity	1
transition metal ion binding	1
cation binding	1
cellular anatomical structure	1
DNA-directed RNA polymerase complex	1
nucleolus	1
nuclear protein-containing complex	1
RNA polymerase complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR1H	POLR1C	O15160	911
POLR1H	POLR1B	Q9H9Y6	847
POLR1H	POLR1G	O15446	842
POLR1H	POLR1F	Q3B726	817
POLR1H	POLI	Q9UNA4	810
POLR1H	POLR2I	P36954	795
POLR1H	POLR2K	P53803	782
POLR1H	POLR2H	P52434	773
POLR1H	POLR3K	Q9Y2Y1	767
POLR1H	TCEA1	P23193	752
POLR1H	TCEA2	Q15560	751
POLR1H	TCEA3	O75764	750
POLR1H	POLR2L	P52436	733
POLR1H	POLR1A	O95602	719
POLR1H	RRN3	Q9NYV6	716
POLR1H	POLR2E	P19388	716

IntAct

36 interactions, top by confidence:

A	B	Type	Score
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
TRIML2	POLR1H	psi-mi:“MI:0915”(physical association)	0.560
POLR1H	GSN	psi-mi:“MI:0915”(physical association)	0.560
POLR1H		psi-mi:“MI:0915”(physical association)	0.560
ATXN1	POLR1H	psi-mi:“MI:0915”(physical association)	0.560
TNS2	POLR1H	psi-mi:“MI:0915”(physical association)	0.370
MAPK8IP2	POLR1H	psi-mi:“MI:0915”(physical association)	0.370
POLR1H	ZNF593	psi-mi:“MI:0915”(physical association)	0.370
POLR1H	APOA1	psi-mi:“MI:0915”(physical association)	0.370
POLR1H	DUSP1	psi-mi:“MI:0915”(physical association)	0.370
POLR1H	GPR20	psi-mi:“MI:0915”(physical association)	0.370
IL15	POLR1H	psi-mi:“MI:0915”(physical association)	0.370
SERPINA3	POLR1H	psi-mi:“MI:0915”(physical association)	0.370
HAX1	POLR1H	psi-mi:“MI:0915”(physical association)	0.370
POLR1H	IVNS1ABP	psi-mi:“MI:0915”(physical association)	0.370
NONO	POLR1H	psi-mi:“MI:0915”(physical association)	0.370
POLR2F	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR1A	POLR2H	psi-mi:“MI:0914”(association)	0.350
PMS2	FAN1	psi-mi:“MI:0914”(association)	0.350
POLR1H	POLR1C	psi-mi:“MI:0914”(association)	0.350
UBR4	METTL15	psi-mi:“MI:0914”(association)	0.350
TRIML2	POLR1H	psi-mi:“MI:0915”(physical association)	0.000
	POLR1H	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (84): ZNRD1 (Two-hybrid), ZNRD1 (Two-hybrid), POLR2E (Co-fractionation), POLR2H (Co-fractionation), ZNRD1 (Two-hybrid), ZNRD1 (Two-hybrid), ZNRD1 (Affinity Capture-MS), ZNRD1 (Affinity Capture-MS), ZNRD1 (Affinity Capture-MS), ZNRD1 (Negative Genetic), ZNRD1 (Positive Genetic), ZNRD1 (Negative Genetic), ZNRD1 (Negative Genetic), ZNRD1 (Affinity Capture-MS), ZNRD1 (Affinity Capture-MS)

ESM2 similar proteins: A4FUD9, B8GGQ3, F4ISQ7, O13896, O27369, O29033, O74635, O94703, O96651, P0CR50, P0CR51, P27999, P32529, P34647, P36078, P52652, P53738, Q04307, Q04673, Q07271, Q09723, Q0J0S6, Q1RMP0, Q1XHV8, Q290L7, Q2FPD4, Q2KIZ8, Q2M2S7, Q498J7, Q54KR5, Q56254, Q5AK73, Q5JL96, Q5R8G6, Q5TM50, Q6CIK2, Q6FS48, Q6MFY5, Q755B3, Q791N7

Diamond homologs: O94703, P32529, Q1RMP0, Q1XHV8, Q5JF34, Q5TM50, Q6MFY5, Q791N7, Q9P1U0, O13896, P0C8F5, P0C8F6, P0C8F7, P0C8F8, P27948, Q07271, Q980K2, O29033, Q04307, Q9ZVH8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
POLR1H	“up-regulates quantity by expression”	ABCB1	“transcriptional regulation”
POLR1H	“up-regulates quantity by expression”	BCL2	“transcriptional regulation”
POLR1H	“form complex”	“RNA Polymerase I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
RNA Polymerase III Transcription Initiation From Type 2 Promoter	5	117.5×	3e-08
RNA Polymerase III Transcription Initiation From Type 1 Promoter	5	113.3×	3e-08
RNA Polymerase III Transcription Initiation From Type 3 Promoter	5	113.3×	3e-08
Positive epigenetic regulation of rRNA expression	5	96.1×	4e-08
RNA Polymerase III Transcription Initiation	5	93.3×	4e-08
RNA Polymerase I Transcription Termination	5	90.6×	4e-08
RNA Polymerase III Transcription	5	90.6×	4e-08
RNA Polymerase I Promoter Clearance	5	81.3×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	5	11.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

582 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30061668:GG:G	donor_gain	1.0000
6:30061669:GG:G	donor_gain	1.0000
6:30061676:GGCTT:G	donor_gain	1.0000
6:30061677:GCTTG:G	donor_gain	1.0000
6:30062222:A:AG	acceptor_gain	1.0000
6:30062223:G:GG	acceptor_gain	1.0000
6:30062329:TGCAA:T	donor_gain	1.0000
6:30062330:GCAA:G	donor_gain	1.0000
6:30062330:GCAAG:G	donor_gain	1.0000
6:30062331:CAA:C	donor_gain	1.0000
6:30062332:AA:A	donor_gain	1.0000
6:30062334:GTGA:G	donor_gain	1.0000
6:30064671:A:C	acceptor_loss	1.0000
6:30064672:G:A	acceptor_loss	1.0000
6:30061324:TTCC:T	donor_gain	0.9900
6:30061394:G:GT	donor_gain	0.9900
6:30061410:G:GT	donor_gain	0.9900
6:30061624:GA:G	donor_gain	0.9900
6:30061667:GGG:G	donor_gain	0.9900
6:30061668:GGG:G	donor_gain	0.9900
6:30061669:GGTGA:G	donor_loss	0.9900
6:30061670:G:GG	donor_gain	0.9900
6:30061670:GTGA:G	donor_loss	0.9900
6:30061678:C:T	donor_gain	0.9900
6:30061995:GGCC:G	donor_gain	0.9900
6:30062222:AG:A	acceptor_gain	0.9900
6:30062223:G:GT	acceptor_loss	0.9900
6:30062223:GG:G	acceptor_gain	0.9900
6:30062331:C:T	donor_gain	0.9900
6:30062337:A:AG	donor_gain	0.9900

AlphaMissense

828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:30062293:G:C	D106H	0.997
6:30062311:T:C	F112L	0.997
6:30062313:C:A	F112L	0.997
6:30062313:C:G	F112L	0.997
6:30061579:T:C	F19L	0.996
6:30061581:C:A	F19L	0.996
6:30061581:C:G	F19L	0.996
6:30062280:G:C	Q101H	0.996
6:30062280:G:T	Q101H	0.996
6:30062291:C:A	A105D	0.996
6:30062236:T:C	C87R	0.995
6:30062266:T:G	Y97D	0.995
6:30062284:C:A	R103S	0.995
6:30062294:A:T	D106V	0.995
6:30062295:T:A	D106E	0.995
6:30062295:T:G	D106E	0.995
6:30062299:G:A	G108R	0.994
6:30062299:G:C	G108R	0.994
6:30062312:T:C	F112S	0.994
6:30062320:T:C	C115R	0.994
6:30062236:T:A	C87S	0.993
6:30062237:G:C	C87S	0.993
6:30062287:T:C	S104P	0.993
6:30062294:A:C	D106A	0.993
6:30062300:G:A	G108E	0.993
6:30062320:T:A	C115S	0.993
6:30062321:G:C	C115S	0.993
6:30061582:T:C	C20R	0.992
6:30062245:T:A	C90S	0.992
6:30062246:G:C	C90S	0.992

dbSNP variants (sampled 300 via entrez): RS1001056901 (6:30058812 A>G), RS1001109117 (6:30059225 T>C), RS1002141658 (6:30059986 G>A), RS1002236045 (6:30058494 C>A), RS1002693551 (6:30058673 CCTGA>C), RS1003323055 (6:30063259 A>G), RS1003414227 (6:30063764 G>A), RS1003930310 (6:30061134 T>A,C), RS1005603451 (6:30063724 C>T), RS1006113721 (6:30064933 C>G), RS1006602894 (6:30062670 C>G), RS1006689075 (6:30062727 T>C,G), RS1006989072 (6:30063174 A>G), RS1007187789 (6:30059328 A>G), RS1007233989 (6:30064309 T>G)

Disease associations

OMIM: gene MIM:607525 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000308_3	AIDS progression	5.000000e-07
GCST000549_24	HIV-1 control	2.000000e-08
GCST000549_5	HIV-1 control	3.000000e-07
GCST002324_6	Anger	8.000000e-07
GCST004521_12	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_121	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_177	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004521_2	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_210	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_216	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_218	Autism spectrum disorder or schizophrenia	5.000000e-11
GCST004521_247	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST004521_263	Autism spectrum disorder or schizophrenia	7.000000e-17
GCST004521_268	Autism spectrum disorder or schizophrenia	7.000000e-12
GCST004521_269	Autism spectrum disorder or schizophrenia	7.000000e-11
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_44	Autism spectrum disorder or schizophrenia	2.000000e-17
GCST004521_51	Autism spectrum disorder or schizophrenia	9.000000e-14
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_58	Autism spectrum disorder or schizophrenia	1.000000e-17
GCST004521_59	Autism spectrum disorder or schizophrenia	1.000000e-11
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST004521_80	Autism spectrum disorder or schizophrenia	1.000000e-15
GCST004521_92	Autism spectrum disorder or schizophrenia	1.000000e-11
GCST004744_22	Lung adenocarcinoma	5.000000e-06
GCST004748_99	Lung cancer	4.000000e-18
GCST004750_49	Squamous cell lung carcinoma	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0003015	aggressive behavior

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
Doxorubicin	increases expression, decreases response to substance, increases secretion, decreases reaction	3
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
4-phenylbutyric acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression, increases abundance	1
Coumestrol	increases expression	1
Etoposide	decreases response to substance, decreases reaction	1
Hydrogen Peroxide	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methotrexate	decreases response to substance	1
Phenobarbital	affects expression	1
Plant Extracts	increases expression, affects cotreatment, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2PY	HAP1 ZNRD1 (-) 1	Cancer cell line	Male
CVCL_E2PZ	HAP1 ZNRD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery